Table of Contents
International Journal of Peptides
Volume 2010, Article ID 879503, 40 pages
http://dx.doi.org/10.1155/2010/879503
Review Article

Integrating GHS into the Ghrelin System

1Department of Medicine, Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, MN 55905, USA
2Division of Endocrinology, Department of Internal Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA

Received 24 September 2009; Accepted 30 December 2009

Academic Editor: Akio Inui

Copyright © 2010 Johannes D. Veldhuis and Cyril Y. Bowers. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. Y. Bowers, J. Chang, F. Momany, and K. Folkers, “Effect of the enkephalins and enkephalin analogs on release of pituitary hormones in vitro,” in Molecular Endocrinology, I. MacIntyre and M. Szelke, Eds., pp. 287–292, Elsevier/North Holland, Amsterdam, The Netherlands, 1977. View at Google Scholar
  2. A. P. Davenport, T. I. Bonner, S. M. Foord et al., “International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function,” Pharmacological Reviews, vol. 57, no. 4, pp. 541–546, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. M. Kojima, H. Hosoda, Y. Date, M. Nakazato, H. Matsuo, and K. Kangawa, “Ghrelin is a growth-hormone-releasing acylated peptide from stomach,” Nature, vol. 402, no. 6762, pp. 656–660, 1999. View at Publisher · View at Google Scholar · View at Scopus
  4. J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, and C. Y. Bowers, “Somatotropic and gonadotropic axes linkages in infancy, childhood, and the puberty-adult transition,” Endocrine Reviews, vol. 27, no. 2, pp. 101–140, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. A. D. Howard, S. D. Feighner, D. F. Cully et al., “A receptor in pituitary and hypothalamus that functions in growth hormone release,” Science, vol. 273, no. 5277, pp. 974–977, 1996. View at Google Scholar · View at Scopus
  6. D. M. Robertson, “Transforming growth factor β/inhibin family,” Bailliere's Clinical Endocrinology and Metabolism, vol. 5, no. 4, pp. 615–634, 1991. View at Google Scholar · View at Scopus
  7. C. Welt, Y. Sidis, H. Keutmann, and A. Schneyer, “Activins, inhibins, and follistatins: from endocrinology to signaling. A paradigm for the new millennium,” Experimental Biology and Medicine, vol. 227, no. 9, pp. 724–752, 2002. View at Google Scholar · View at Scopus
  8. M. Bagnasco, G. Tulipano, M. R. Melis, A. Argiolas, D. Cocchi, and E. E. Muller, “Endogenous ghrelin is an orexigenic peptide acting in the arcuate nucleus in response to fasting,” Regulatory Peptides, vol. 111, no. 1–3, pp. 161–167, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. T. Sato, Y. Fukue, H. Teranishi, Y. Yoshida, and M. Kojima, “Molecular forms of hypothalamic ghrelin and its regulation by fasting and 2-deoxy-D-glucose administration,” Endocrinology, vol. 146, no. 6, pp. 2510–2516, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. H. Kageyama, Y. Kitamura, T. Hosono et al., “Visualization of ghrelin-producing neurons in the hypothalamic arcuate nucleus using ghrelin-EGFP transgenic mice,” Regulatory Peptides, vol. 145, no. 1–3, pp. 116–121, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. J. Menyhért, G. Wittmann, E. Hrabovszky et al., “Distribution of ghrelin-immunoreactive neuronal networks in the human hypothalamus,” Brain Research, vol. 1125, no. 1, pp. 31–36, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. J. E. Caminos, O. Gualillo, F. Lago et al., “The endogenous growth hormone secretagogue (ghrelin) is synthesized and secreted by chondrocytes,” Endocrinology, vol. 146, no. 3, pp. 1285–1292, 2005. View at Publisher · View at Google Scholar · View at Scopus
  13. J.-B. Soares, A. Rocha-Sousa, P. Castro-Chaves, T. Henriques-Coelho, and A. F. Leite-Moreira, “Inotropic and lusitropic effects of ghrelin and their modulation by the endocardial endothelium, NO, prostaglandins, GHS-R1a and KCa channels,” Peptides, vol. 27, no. 7, pp. 1616–1623, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. X. Xu, S. J. Bong, H. H. Chang, and Z.-G. Jin, “Molecular mechanisms of ghrelin-mediated endothelial nitric oxide synthase activation,” Endocrinology, vol. 149, no. 8, pp. 4183–4192, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Kui, Z. Weiwei, L. ling et al., “Ghrelin inhibits apoptosis induced by high glucose and sodium palmitate in adult rat cardiomyocytes through the PI3K-Akt signaling pathway,” Regulatory Peptides, vol. 155, no. 1–3, pp. 62–69, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. F. Rodríguez-Pacheco, R. M. Luque, M. Tena-Sempere, M. M. Malagón, and J. P. Castaño, “Ghrelin induces growth hormone secretion via a nitric oxide/cGMP signalling pathway,” Journal of Neuroendocrinology, vol. 20, no. 3, pp. 406–412, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. H. M. Bilgin, C. Tumer, H. Diken, M. Kelle, and A. Sermet, “Role of ghrelin in the regulation of gastric acid secretion involving nitrergic mechanisms in rats,” Physiological Research, vol. 57, no. 4, pp. 563–568, 2008. View at Google Scholar · View at Scopus
  18. F. S. Gaskin, S. A. Farr, W. A. Banks, V. B. Kumar, and J. E. Morley, “Ghrelin-induced feeding is dependent on nitric oxide,” Peptides, vol. 24, no. 6, pp. 913–918, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. P. C. Konturek, T. Brzozowski, B. Walter et al., “Ghrelin-induced gastroprotection against ischemia-reperfusion injury involves an activation of sensory afferent nerves and hyperemia mediated by nitric oxide,” European Journal of Pharmacology, vol. 536, no. 1-2, pp. 171–181, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. M. Iantorno, H. Chen, J.-A. Kim et al., “Ghrelin has novel vascular actions that mimic PI 3-kinase-dependent actions of insulin to stimulate production of NO from endothelial cells,” American Journal of Physiology, vol. 292, no. 3, pp. E756–E764, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. H. Chung, S. Seo, M. Moon, and S. Park, “Phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-3β and ERK1/2 pathways mediate protective effects of acylated and unacylated ghrelin against oxygen-glucose deprivation-induced apoptosis in primary rat cortical neuronal cells,” Journal of Endocrinology, vol. 198, no. 3, pp. 511–521, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. G. Baldanzi, N. Filigheddu, S. Cutrupi et al., “Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT,” Journal of Cell Biology, vol. 159, no. 6, pp. 1029–1037, 2002. View at Publisher · View at Google Scholar · View at Scopus
  23. J. Rivier, J. Spiess, M. Thorner, and W. Vale, “Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour,” Nature, vol. 300, no. 5889, pp. 276–278, 1982. View at Google Scholar · View at Scopus
  24. R. Guillemin, P. Brazeau, P. Bohlen, F. Esch, N. Ling, and W. B. Wehrenberg, “Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly,” Science, vol. 218, no. 4572, pp. 585–587, 1982. View at Google Scholar · View at Scopus
  25. K. E. Mayo, P. A. Godfrey, S. T. Suhr, D. J. Kulik, and J. O. Rahal, “Growth hormone-releasing hormone: synthesis and signaling,” Recent Progress in Hormone Research, vol. 50, no. 1, pp. 35–73, 1995. View at Google Scholar · View at Scopus
  26. M. Kojima and K. Kangawa, “Ghrelin: structure and function,” Physiological Reviews, vol. 85, no. 2, pp. 495–522, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. J. Pantel, M. Legendre, S. Cabrol et al., “Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature,” Journal of Clinical Investigation, vol. 116, no. 3, pp. 760–768, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Lall, N. Balthasar, D. Carmignac et al., “Physiological studies of transgenic mice overexpressing growth hormone (GH) secretagogue receptor 1A in GH-releasing hormone neurons,” Endocrinology, vol. 145, no. 4, pp. 1602–1611, 2004. View at Publisher · View at Google Scholar · View at Scopus
  29. L. Di Vito, F. Broglio, A. Benso et al., “The GH-releasing effect of ghrelin, a natural GH secretagogue, is only blunted by the infusion of exogenous somatostatin in humans,” Clinical Endocrinology, vol. 56, no. 5, pp. 643–648, 2002. View at Publisher · View at Google Scholar · View at Scopus
  30. C. D. McMahon, L. T. Chapin, R. P. Radcliff, K. J. Lookingland, and H. A. Tucker, “GH-releasing peptide-6 overcomes refractoriness of somatotropes to GHRH after feeding,” Journal of Endocrinology, vol. 170, no. 1, pp. 235–241, 2001. View at Publisher · View at Google Scholar · View at Scopus
  31. S. L. Dickson, O. Viltart, A. R. T. Bailey, and G. Leng, “Attenuation of the growth hormone secretagogue induction of fos protein in the rat arcuate nucleus by central somatostatin action,” Neuroendocrinology, vol. 66, no. 3, pp. 188–194, 1997. View at Google Scholar · View at Scopus
  32. V. Tolle, P. Zizzari, C. Tomasetto, M.-C. Rio, J. Epelbaum, and M.-T. Bluet-Pajot, “In vivo and in vitro effects of ghrelin/motilin-related peptide on growth hormone secretion in the rat,” Neuroendocrinology, vol. 73, no. 1, pp. 54–61, 2001. View at Publisher · View at Google Scholar · View at Scopus
  33. J. Herrington and B. Hille, “Growth hormone-releasing hexapeptide elevates intracellular calcium in rat somatotropes by two mechanisms,” Endocrinology, vol. 135, no. 3, pp. 1100–1108, 1994. View at Publisher · View at Google Scholar · View at Scopus
  34. T. Hashizume, M. Horiuchi, N. Tate et al., “Effects of ghrelin on growth hormone secretion from cultured adenohypophysial cells in cattle,” Endocrine Journal, vol. 50, no. 3, pp. 289–295, 2003. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Traebert, T. Riediger, S. Whitebread, E. Scharrer, and H. A. Schmid, “Ghrelin acts on leptin-responsive neurones in the rat arcuate nucleus,” Journal of Neuroendocrinology, vol. 14, no. 7, pp. 580–586, 2002. View at Publisher · View at Google Scholar · View at Scopus
  36. J. Menyhert, G. Wittmann, E. Hrabovszky, E. Keller, Z. Liposits, and C. Fekete, “Interconnection between orexigenic neuropeptide Y- and anorexigenic α-melanocyte stimulating hormone-synthesizing neuronal systems of the human hypothalamus,” Brain Research, vol. 1076, no. 1, pp. 101–105, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. A. M. Wren, L. J. Seal, M. A. Cohen et al., “Ghrelin enhances appetite and increases food intake in humans,” The Journal of Clinical Endocrinology & Metabolism, vol. 86, no. 12, pp. 5992–5995, 2001. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Shintani, Y. Ogawa, K. Ebihara et al., “Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway,” Diabetes, vol. 50, no. 2, pp. 227–232, 2001. View at Google Scholar · View at Scopus
  39. M. Nakazato, N. Murakami, Y. Date et al., “A role for ghrelin in the central regulation of feeding,” Nature, vol. 409, no. 6817, pp. 194–198, 2001. View at Publisher · View at Google Scholar · View at Scopus
  40. Y. C. L. Tung, A. K. Hewson, and S. L. Dickson, “Actions of leptin on growth hormone secretagogue-responsive neurones in the rat hypothalamic arcuate nucleus recorded in vitro,” Journal of Neuroendocrinology, vol. 13, no. 2, pp. 209–215, 2001. View at Publisher · View at Google Scholar · View at Scopus
  41. L. S. Farhy and J. D. Veldhuis, “Deterministic construct of amplifying actions of ghrelin on pulsatile growth hormone secretion,” American Journal of Physiology, vol. 288, no. 6, pp. R1649–R1663, 2005. View at Publisher · View at Google Scholar · View at Scopus
  42. J. Kamegai, H. Tamura, T. Shimizu, S. Ishii, H. Sugihara, and S. Oikawa, “Regulation of the ghrelin gene: growth hormone-releasing hormone upregulates ghrelin mRNA in the pituitary,” Endocrinology, vol. 142, no. 9, pp. 4154–4157, 2001. View at Publisher · View at Google Scholar · View at Scopus
  43. A. Inui, “Ghrelin: an orexigenic and somatotrophic signal from the stomach,” Nature Reviews Neuroscience, vol. 2, no. 8, pp. 551–560, 2001. View at Publisher · View at Google Scholar · View at Scopus
  44. A. Abizaid, Z.-W. Liu, Z. B. Andrews et al., “Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite,” Journal of Clinical Investigation, vol. 116, no. 12, pp. 3229–3239, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Tang-Christensen, N. Vrang, S. Ortmann, M. Bidlingmaier, T. L. Horvath, and M. Tschöp, “Central administration of ghrelin and agouti-related protein (83–132) increases food intake and decreases spontaneous locomotor activity in rats,” Endocrinology, vol. 145, no. 10, pp. 4645–4652, 2004. View at Publisher · View at Google Scholar · View at Scopus
  46. J. Yang, T.-J. Zhao, J. L. Goldstein, and M. S. Brown, “Inhibition of ghrelin O-acyltransferase (GOAT) by octanoylated pentapeptides,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 31, pp. 10750–10755, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. J. Yang, M. S. Brown, G. Liang, N. V. Grishin, and J. L. Goldstein, “Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone,” Cell, vol. 132, no. 3, pp. 387–396, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. J. A. Gutierrez, P. J. Solenberg, D. R. Perkins et al., “Ghrelin octanoylation mediated by an orphan lipid transferase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 17, pp. 6320–6325, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. S.-C. Chang and A. I. Magee, “Acyltransferases for secreted signalling proteins (Review),” Molecular Membrane Biology, vol. 26, no. 1-2, pp. 104–113, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. H. Kirchner, J. A. Gutierrez, P. J. Solenberg et al., “GOAT links dietary lipids with the endocrine control of energy balance,” Nature Medicine, vol. 15, no. 7, pp. 741–745, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. A. W. Root and M. J. Root, “Clinical pharmacology of human growth hormone and its secretagogues,” Current Drug Targets. Immune, Endocrine and Metabolic Disorders, vol. 2, no. 1, pp. 27–52, 2002. View at Google Scholar · View at Scopus
  52. C. R. González, M. J. Vázquez, M. López, and C. Diéguez, “Influence of chronic undernutrition and leptin on GOAT mRNA levels in rat stomach mucosa,” Journal of Molecular Endocrinology, vol. 41, no. 5-6, pp. 415–421, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. I. Sakata, J. Yang, C. E. Lee et al., “Colocalization of ghrelin O-acyltransferase and ghrelin in gastric mucosal cells,” American Journal of Physiology, vol. 297, no. 1, pp. E134–E141, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. I. Seim, C. Collet, A. C. Herington, and L. K. Chopin, “Revised genomic structure of the human ghrelin gene and identification of novel exons, alternative splice variants and natural antisense transcripts,” BMC Genomics, vol. 8, article 298, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. I. Seim, L. Amorim, C. Walpole, S. Carter, L. K. Chopin, and A. C. Herington, “Ghrelin gene-related peptides: multifunctional endocrine/autocrine modulators in health and disease,” Clinical and Experimental Pharmacology and Physiology, vol. 37, no. 1, pp. 125–131, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. A. Ozawa, R. B. Speaker III, and I. Lindberg, “Enzymatic characterization of a human acyltransferase activity,” PLoS ONE, vol. 4, no. 5, article e5426, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. C. Gauna, B. van de Zande, A. van Kerkwijk, A. P. N. Themmen, A. J. van der Lely, and P. J. D. Delhanty, “Unacylated ghrelin is not a functional antagonist but a full agonist of the type 1a growth hormone secretagogue receptor (GHS-R),” Molecular and Cellular Endocrinology, vol. 274, no. 1-2, pp. 30–34, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. Y. Shanado, M. Kometani, H. Uchiyama, S. Koizumi, and N. Teno, “Lysophospholipase I identified as a ghrelin deacylation enzyme in rat stomach,” Biochemical and Biophysical Research Communications, vol. 325, no. 4, pp. 1487–1494, 2004. View at Publisher · View at Google Scholar · View at Scopus
  59. H. Hosoda, K. Doi, N. Nagaya et al., “Optimum collection and storage conditions for ghrelin measurements: octanoyl modification of ghrelin is rapidly hydrolyzed to desacyl ghrelin in blood samples,” Clinical Chemistry, vol. 50, no. 6, pp. 1077–1080, 2004. View at Publisher · View at Google Scholar · View at Scopus
  60. H. Ohgusu, K. Shirouzu, Y. Nakamura et al., “Ghrelin O-acyltransferase (GOAT) has a preference for n-hexanoyl-CoA over n-octanoyl-CoA as an acyl donor,” Biochemical and Biophysical Research Communications, vol. 386, no. 1, pp. 153–158, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. H. Hosoda, M. Kojima, H. Matsuo, and K. Kangawa, “Purification and characterization of rat des-Gln14-ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor,” Journal of Biological Chemistry, vol. 275, no. 29, pp. 21995–22000, 2000. View at Publisher · View at Google Scholar · View at Scopus
  62. H. Kaiya, M. Miyazato, K. Kangawa, R. E. Peter, and S. Unniappan, “Ghrelin: a multifunctional hormone in non-mammalian vertebrates,” Comparative Biochemistry and Physiology Part A, vol. 149, no. 2, pp. 109–128, 2008. View at Publisher · View at Google Scholar · View at Scopus
  63. R. G. Smith, R. Leonard, A. R. T. Bailey et al., “Growth hormone secretagogue receptor family members and ligands,” Endocrine, vol. 14, no. 1, pp. 9–14, 2001. View at Google Scholar · View at Scopus
  64. E. Codner, F. Cassorla, A. N. Tiulpakov et al., “Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone-insulin-like growth factor I axis in growth hormone-deficient children,” Clinical Pharmacology and Therapeutics, vol. 70, no. 1, pp. 91–98, 2001. View at Publisher · View at Google Scholar · View at Scopus
  65. C. Y. Bowers, J.-K. Chang, S. Wu, K. D. Linse, D. L. Hurley, and J. D. Veldhuis, “Biochemistry of the growth hormone-releasing peptides, secretagogues and ghrelin,” in Cachexia and Wasting: A Modern Approach, G. Mantovani, S. D. Anker, A. Inui et al., Eds., pp. 219–234, Springer, New York, NY, USA, 2006. View at Google Scholar
  66. N. K. Aagaard, T. Grøfte, J. Greisen et al., “Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats,” Growth Hormone and IGF Research, vol. 19, no. 5, pp. 426–431, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. K. Raun, B. S. Hansen, N. L. Johansen et al., “Ipamorelin, the first selective growth hormone secretagogue,” European Journal of Endocrinology, vol. 139, no. 5, pp. 552–561, 1998. View at Google Scholar · View at Scopus
  68. C. J. Pemberton and A. M. Richards, “Biochemistry of ghrelin precursor peptides,” Vitamins & Hormones, vol. 77, pp. 13–30, 2007. View at Publisher · View at Google Scholar · View at Scopus
  69. C. Pemberton, P. Wimalasena, T. Yandle, S. Soule, and M. Richards, “C-terminal pro-ghrelin peptides are present in the human circulation,” Biochemical and Biophysical Research Communications, vol. 310, no. 2, pp. 567–573, 2003. View at Publisher · View at Google Scholar · View at Scopus
  70. E. Ingelsson, M. G. Larson, X. Yin et al., “Circulating ghrelin, leptin, and soluble leptin receptor concentrations and cardiometabolic risk factors in a community-based sample,” The Journal of Clinical Endocrinology & Metabolism, vol. 93, no. 8, pp. 3149–3157, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. J. Q. Purnell, D. S. Weigle, P. Breen, and D. E. Cummings, “Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans,” The Journal of Clinical Endocrinology & Metabolism, vol. 88, no. 12, pp. 5747–5752, 2003. View at Publisher · View at Google Scholar · View at Scopus
  72. H. Hosoda, M. Kojima, T. Mizushima, S. Shimizu, and K. Kangawa, “Structural divergence of human ghrelin: identification of multiple ghrelin-derived molecules produced by post-translational processing,” Journal of Biological Chemistry, vol. 278, no. 1, pp. 64–70, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. K. Chandarana, M. E. Drew, J. Emmanuel et al., “Subject standardization, acclimatization, and sample processing affect gut hormone levels and appetite in humans,” Gastroenterology, vol. 136, no. 7, pp. 2115–2126, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. K. Toshinai, H. Yamaguchi, Y. Sun et al., “Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor,” Endocrinology, vol. 147, no. 5, pp. 2306–2314, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. H. Ariyasu, K. Takaya, H. Iwakura et al., “Transgenic mice overexpressing des-acyl ghrelin show small phenotype,” Endocrinology, vol. 146, no. 1, pp. 355–364, 2005. View at Publisher · View at Google Scholar · View at Scopus
  76. N. M. Thompson, D. A. S. Gill, R. Davies et al., “Ghrelin and des-octanoyl ghrelin promote adipogenesis directlyin vivo by a mechanism independent of GHS-R1a,” Endocrinology, vol. 145, no. 1, pp. 234–242, 2004. View at Publisher · View at Google Scholar · View at Scopus
  77. F. Broglio, L. Gianotti, S. Destefanis et al., “The endocrine response to acute ghrelin administration is blunted in patients with anorexia nervosa, a ghrelin hypersecretory state,” Clinical Endocrinology, vol. 60, no. 5, pp. 592–599, 2004. View at Publisher · View at Google Scholar · View at Scopus
  78. J. Dong, T. L. Peeters, B. De Smet et al., “Role of endogenous ghrelin in the hyperphagia of mice with streptozotocin-induced diabetes,” Endocrinology, vol. 147, no. 6, pp. 2634–2642, 2006. View at Publisher · View at Google Scholar · View at Scopus
  79. M. Tanaka, T. Nakahara, S. Kojima et al., “Effect of nutritional rehabilitation on circulating ghrelin and growth hormone levels in patients with anorexia nervosa,” Regulatory Peptides, vol. 122, no. 3, pp. 163–168, 2004. View at Publisher · View at Google Scholar · View at Scopus
  80. A. Troisi, G. Di Lorenzo, I. Lega et al., “Plasma ghrelin in anorexia, bulimia, and binge-eating disorder: relations with eating patterns and circulating concentrations of cortisol and thyroid hormones,” Neuroendocrinology, vol. 81, no. 4, pp. 259–266, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. K. Toshinai, M. S. Mondal, M. Nakazato et al., “Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration,” Biochemical and Biophysical Research Communications, vol. 281, no. 5, pp. 1220–1225, 2001. View at Publisher · View at Google Scholar · View at Scopus
  82. A. Gambineri, U. Pagotto, R. De Iasio et al., “Short-term modification of sex hormones is associated with changes in ghrelin circulating levels in healthy normal-weight men,” Journal of Endocrinological Investigation, vol. 28, no. 3, pp. 241–246, 2005. View at Google Scholar · View at Scopus
  83. T. Itoh, N. Nagaya, M. Yoshikawa et al., “Elevated plasma ghrelin level in underweight patients with chronic obstructive pulmonary disease,” American Journal of Respiratory and Critical Care Medicine, vol. 170, no. 8, pp. 879–882, 2004. View at Publisher · View at Google Scholar · View at Scopus
  84. C. Gottero, F. Broglio, F. Prodam et al., “Ghrelin: a link between eating disorders, obesity and reproduction,” Nutritional Neuroscience, vol. 7, no. 5-6, pp. 255–270, 2004. View at Publisher · View at Google Scholar · View at Scopus
  85. G. Vila, C. Maier, M. Riedl et al., “Bacterial endotoxin induces biphasic changes in plasma ghrelin in healthy humans,” The Journal of Clinical Endocrinology & Metabolism, vol. 92, no. 10, pp. 3930–3934, 2007. View at Publisher · View at Google Scholar · View at Scopus
  86. A. Yoshimoto, K. Mori, A. Sugawara et al., “Plasma ghrelin and desacyl ghrelin concentrations in renal failure,” Journal of the American Society of Nephrology, vol. 13, no. 11, pp. 2748–2752, 2002. View at Publisher · View at Google Scholar · View at Scopus
  87. L. Ryber, K. Obrink, N. Houe, J. Frystyk, and J. O. L. Jorgensen, “Serum ghrelin levels are suppressed in hypopituitary patients following insulin-induced hypoglycaemia irrespective of GH status,” Clinical Endocrinology, vol. 65, no. 2, pp. 210–214, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. W. Wei, G. Wang, X. Qi, E. W. Englander, and G. H. Greeley Jr., “Characterization and regulation of the rat and human ghrelin promoters,” Endocrinology, vol. 146, no. 3, pp. 1611–1625, 2005. View at Publisher · View at Google Scholar · View at Scopus
  89. H. Matsuoka, H. Hosoda, H. Sugawara et al., “Short-term secretory regulation of ghrelin during growth hormone provocative tests in prepubertal children with various growth hormone secretory capacities,” Hormone Research, vol. 64, no. 6, pp. 274–279, 2005. View at Publisher · View at Google Scholar · View at Scopus
  90. H. Hiejima, Y. Nishi, H. Hosoda et al., “Regional distribution and the dynamics of n-decanoyl ghrelin, another acyl-form of ghrelin, upon fasting in rodents,” Regulatory Peptides, vol. 156, no. 1–3, pp. 47–56, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. R. C. Paulo, R. Brundage, M. Cosma, K. L. Mielke, C. Y. Bowers, and J. D. Veldhuis, “Estrogen elevates the peak overnight production rate of acylated ghrelin,” The Journal of Clinical Endocrinology & Metabolism, vol. 93, no. 11, pp. 4440–4447, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. A. L. Barkan, E. V. Dimaraki, S. K. Jessup, K. V. Symons, M. Ermolenko, and C. A. Jaffe, “Ghrelin secretion in humans is sexually dimorphic, suppressed by somatostatin, and not affected by the ambient growth hormone levels,” The Journal of Clinical Endocrinology & Metabolism, vol. 88, no. 5, pp. 2180–2184, 2003. View at Publisher · View at Google Scholar · View at Scopus
  93. A. J. Whatmore, C. M. Hall, J. Jones, M. Westwood, and P. E. Clayton, “Ghrelin concentrations in healthy children and adolescents,” Clinical Endocrinology, vol. 59, no. 5, pp. 649–654, 2003. View at Publisher · View at Google Scholar · View at Scopus
  94. A. L. D. Riis, T. K. Hansen, N. Møller, J. Weeke, and J. O. L. Jorgensen, “Hyperthyroidism is associated with suppressed circulating ghrelin levels,” The Journal of Clinical Endocrinology & Metabolism, vol. 88, no. 2, pp. 853–857, 2003. View at Publisher · View at Google Scholar · View at Scopus
  95. Y. Makino, H. Hosoda, K. Shibata et al., “Alteration of plasma ghrelin levels associated with the blood pressure in pregnancy,” Hypertension, vol. 39, no. 3, pp. 781–784, 2002. View at Publisher · View at Google Scholar · View at Scopus
  96. S. M. Pöykkö, E. Kellokoski, S. Hörkkö, H. Kauma, Y. A. Kesäniemi, and O. Ukkola, “Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes,” Diabetes, vol. 52, no. 10, pp. 2546–2553, 2003. View at Publisher · View at Google Scholar · View at Scopus
  97. H. Norrelund, T. K. Hansen, H. Orskov et al., “Ghrelin immunoreactivity in human plasma is suppressed by somatostatin,” Clinical Endocrinology, vol. 57, no. 4, pp. 539–546, 2002. View at Publisher · View at Google Scholar · View at Scopus
  98. T. Akamizu, T. Murayama, S. Teramukai et al., “Plasma ghrelin levels in healthy elderly volunteers: the levels acylated ghrelin in elderly females correlate positively with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure,” Journal of Endocrinology, vol. 188, no. 2, pp. 333–344, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. S. Grinspoon, K. K. Miller, D. B. Herzog, K. A. Grieco, and A. Klibanski, “Effects of estrogen and recombinant human insulin-like growth factor-I on ghrelin secretion in severe undernutrition,” The Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 8, pp. 3988–3993, 2004. View at Publisher · View at Google Scholar · View at Scopus
  100. E. Kellokoski, S. M. Pöykkö, A. H. Karjalainen et al., “Estrogen replacement therapy increases plasma ghrelin levels,” The Journal of Clinical Endocrinology & Metabolism, vol. 90, no. 5, pp. 2954–2963, 2005. View at Publisher · View at Google Scholar · View at Scopus
  101. C. Di Carlo, G. A. Tommaselli, V. Gargano et al., “Effects of estrogen-progestin therapy on serum levels of RANKL, osteoprotegerin, osteocalcin, leptin, and ghrelin in postmenopausal women,” Menopause, vol. 14, no. 1, pp. 38–44, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. C. I. Messini, K. Dafopoulos, N. Chalvatzas, P. Georgoulias, and I. E. Messinis, “Growth hormone and prolactin response to ghrelin during the normal menstrual cycle,” Clinical Endocrinology, vol. 71, no. 3, pp. 383–387, 2009. View at Publisher · View at Google Scholar · View at Scopus
  103. M. Matsubara, I. Sakata, R. Wada, M. Yamazaki, K. Inoue, and T. Sakai, “Estrogen modulates ghrelin expression in the female rat stomach,” Peptides, vol. 25, no. 2, pp. 289–297, 2004. View at Publisher · View at Google Scholar · View at Scopus
  104. C. Maffeis, R. Franceschi, P. Moghetti, M. Camilot, S. Lauriola, and L. Tato, “Circulating ghrelin levels in girls with central precocious puberty are reduced during treatment with LHRH analog,” European Journal of Endocrinology, vol. 156, no. 1, pp. 99–103, 2007. View at Publisher · View at Google Scholar · View at Scopus
  105. Y. Lebenthal, G. Gat-Yablonski, B. Shtaif, A. Padoa, M. Phillip, and L. Lazar, “Effect of sex hormone administration on circulating ghrelin levels in peripubertal children,” The Journal of Clinical Endocrinology & Metabolism, vol. 91, no. 1, pp. 328–331, 2006. View at Publisher · View at Google Scholar · View at Scopus
  106. P. Villa, B. Costantini, C. Perri, R. Suriano, L. Ricciardi, and A. Lanzone, “Estro-progestin supplementation enhances the growth hormone secretory responsiveness to ghrelin infusion in postmenopausal women,” Fertility and Sterility, vol. 89, no. 2, pp. 398–403, 2008. View at Publisher · View at Google Scholar · View at Scopus
  107. P. Kok, R. C. Paulo, M. Cosma et al., “Estrogen supplementation selectively enhances hypothalamo-pituitary sensitivity to ghrelin in postmenopausal women,” The Journal of Clinical Endocrinology & Metabolism, vol. 93, no. 10, pp. 4020–4026, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. M. Cappa, S. Setzu, S. Bernardini et al., “Exogenous growth hormone administration does not inhibit the growth hormone response to hexarelin in normal men,” Journal of Endocrinological Investigation, vol. 18, no. 10, pp. 762–766, 1995. View at Google Scholar · View at Scopus
  109. S. Loche, A. Colao, M. Cappa et al., “The growth hormone response to hexarelin in children: reproducibility and effect of sex steroids,” The Journal of Clinical Endocrinology & Metabolism, vol. 82, no. 3, pp. 861–864, 1997. View at Publisher · View at Google Scholar · View at Scopus
  110. J. D. Veldhuis, D. M. Keenan, A. Iranmanesh, K. Mielke, J. M. Miles, and C. Y. Bowers, “Estradiol potentiates ghrelin-stimulated pulsatile growth hormone secretion in postmenopausal women,” The Journal of Clinical Endocrinology & Metabolism, vol. 91, no. 9, pp. 3559–3565, 2006. View at Publisher · View at Google Scholar · View at Scopus
  111. S. M. Anderson, L. Wideman, J. T. Patrie, A. Weltman, C. Y. Bowers, and J. D. Veldhuis, “E2 supplementation selectively relieves GH's autonegative feedback on GH-releasing peptide-2-stimulated GH secretion,” The Journal of Clinical Endocrinology & Metabolism, vol. 86, no. 12, pp. 5904–5911, 2001. View at Publisher · View at Google Scholar · View at Scopus
  112. S. M. Anderson, N. Shah, W. S. Evans, J. T. Patrie, C. Y. Bowers, and J. D. Veldhuis, “Short-term estradiol supplementation augments growth hormone (GH) secretory responsiveness to dose-varying GH-releasing peptide infusions in healthy postmenopausal women,” The Journal of Clinical Endocrinology & Metabolism, vol. 86, no. 2, pp. 551–560, 2001. View at Publisher · View at Google Scholar · View at Scopus
  113. F. Broglio, A. Benso, C. Castiglioni et al., “The endocrine response to ghrelin as a function of gender in humans in young and elderly subjects,” The Journal of Clinical Endocrinology & Metabolism, vol. 88, no. 4, pp. 1537–1542, 2003. View at Publisher · View at Google Scholar · View at Scopus
  114. J. D. Veldhuis, D. M. Keenan, K. Mielke, J. M. Miles, and C. Y. Bowers, “Testosterone supplementation in healthy older men drives GH and IGF-I secretion without potentiating peptidyl secretagogue efficacy,” European Journal of Endocrinology, vol. 153, no. 4, pp. 577–586, 2005. View at Publisher · View at Google Scholar · View at Scopus
  115. A. E. Rigamonti, S. G. Cella, C. Giordani et al., “Testosterone inhibition of growth hormone release stimulated by a growth hormone secretagogue: studies in the rat and dog,” Neuroendocrinology, vol. 84, no. 2, pp. 115–122, 2007. View at Publisher · View at Google Scholar · View at Scopus
  116. T. K. Hansen, R. Dall, H. Hosoda et al., “Weight loss increases circulating levels of ghrelin in human obesity,” Clinical Endocrinology, vol. 56, no. 2, pp. 203–206, 2002. View at Publisher · View at Google Scholar · View at Scopus
  117. L. C. Gormsen, C. Nielsen, J. Gjedsted et al., “Effects of free fatty acids, growth hormone and growth hormone receptor blockade on serum ghrelin levels in humans,” Clinical Endocrinology, vol. 66, no. 5, pp. 641–645, 2007. View at Publisher · View at Google Scholar · View at Scopus
  118. R. Nass, J. Liu, P. Hellmann et al., “Chronic changes in peripheral growth hormone levels do not affect ghrelin stomach mRNA expression and serum ghrelin levels in three transgenic mouse models,” Journal of Neuroendocrinology, vol. 16, no. 8, pp. 669–675, 2004. View at Publisher · View at Google Scholar · View at Scopus
  119. J. A. Janssen, F. M. van der Toorn, L. J. Hofland et al., “Systemic ghrelin levels in subjects with growth hormone deficiency are not modified by one year of growth hormone replacement therapy,” European Journal of Endocrinology, vol. 145, no. 6, pp. 711–716, 2001. View at Google Scholar · View at Scopus
  120. R. Dall, J. Kanaley, T. K. Hansen et al., “Plasma ghrelin levels during exercise in healthy subjects and in growth hormone-deficient patients,” European Journal of Endocrinology, vol. 147, no. 1, pp. 65–70, 2002. View at Google Scholar · View at Scopus
  121. A. M. Arafat, F. H. Perschel, B. Otto et al., “Glucagon suppression of ghrelin secretion is exerted at hypothalamus-pituitary level,” The Journal of Clinical Endocrinology & Metabolism, vol. 91, no. 9, pp. 3528–3533, 2006. View at Publisher · View at Google Scholar · View at Scopus
  122. H. Kaji, M. Kishimoto, T. Kirimura et al., “Hormonal regulation of the human ghrelin receptor gene transcription,” Biochemical and Biophysical Research Communications, vol. 284, no. 3, pp. 660–666, 2001. View at Publisher · View at Google Scholar · View at Scopus
  123. D. J. Clegg, L. M. Brown, J. M. Zigman et al., “Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats,” Diabetes, vol. 56, no. 4, pp. 1051–1058, 2007. View at Publisher · View at Google Scholar · View at Scopus
  124. T. Katayama, S. Shimamoto, H. Oda, K. Nakahara, K. Kangawa, and N. Murakami, “Glucagon receptor expression and glucagon stimulation of ghrelin secretion in rat stomach,” Biochemical and Biophysical Research Communications, vol. 357, no. 4, pp. 865–870, 2007. View at Publisher · View at Google Scholar · View at Scopus
  125. C.-Y. Chen, M. Fujimiya, A. Asakawa et al., “At the cutting edge: ghrelin gene products in food intake and gut motility,” Neuroendocrinology, vol. 89, no. 1, pp. 9–17, 2009. View at Publisher · View at Google Scholar · View at Scopus
  126. L. Friis-Hansen, N. Wierup, J. F. Rehfeld, and F. Sundler, “Reduced ghrelin, islet amyloid polypeptide, and peptide YY expression in the stomach of gastrin-cholecystokinin knockout mice,” Endocrinology, vol. 146, no. 10, pp. 4464–4471, 2005. View at Publisher · View at Google Scholar · View at Scopus
  127. M. Arakawa, H. Suzuki, Y. Minegishi et al., “Enhanced ghrelin expression and subsequent acid secretion in mice with genetic H2-receptor knockout,” Journal of Gastroenterology, vol. 42, no. 9, pp. 711–718, 2007. View at Publisher · View at Google Scholar · View at Scopus
  128. F. Broglio, P. Van Koetsveld, A. Benso et al., “Ghrelin secretion is inhibited by either somatostatin or cortistatin in humans,” The Journal of Clinical Endocrinology & Metabolism, vol. 87, no. 10, pp. 4829–4832, 2002. View at Publisher · View at Google Scholar · View at Scopus
  129. K. L. Teff, S. S. Elliott, M. Tschöp et al., “Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women,” The Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 6, pp. 2963–2972, 2004. View at Publisher · View at Google Scholar · View at Scopus
  130. D. E. Flanagan, M. L. Evans, T. P. Monsod et al., “The influence of insulin on circulating ghrelin,” American Journal of Physiology, vol. 284, no. 2, pp. E313–E316, 2003. View at Google Scholar · View at Scopus
  131. H. Takahashi, A. Kato, K. Onodera, and K. Suzuki, “Fasting plasma ghrelin levels reflect malnutrition state in patients with liver cirrhosis,” Hepatology Research, vol. 34, no. 2, pp. 117–123, 2006. View at Publisher · View at Google Scholar · View at Scopus
  132. Z. Jarkovská, M. Hodková, M. Sazamová et al., “Plasma levels of active and total ghrelin in renal failure: a relationship with GH/IGF-I axis,” Growth Hormone and IGF Research, vol. 15, no. 6, pp. 369–376, 2005. View at Publisher · View at Google Scholar · View at Scopus
  133. M. Kojima and K. Kangawa, “Drug insight: the functions of ghrelin and its potential as a multitherapeutic hormone,” Nature Clinical Practice Endocrinology and Metabolism, vol. 2, no. 2, pp. 80–88, 2006. View at Publisher · View at Google Scholar · View at Scopus
  134. K. L. Feltrin, M. Patterson, M. A. Ghatei et al., “Effect of fatty acid chain length on suppression of ghrelin and stimulation of PYY, GLP-2 and PP secretion in healthy men,” Peptides, vol. 27, no. 7, pp. 1638–1643, 2006. View at Publisher · View at Google Scholar · View at Scopus
  135. W. A. M. Blom, A. Lluch, A. Stafleu et al., “Effect of a high-protein breakfast on the postprandial ghrelin response,” American Journal of Clinical Nutrition, vol. 83, no. 2, pp. 211–220, 2006. View at Google Scholar · View at Scopus
  136. B. Otto, U. Cuntz, E. Fruehauf et al., “Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa,” European Journal of Endocrinology, vol. 145, no. 5, pp. 669–673, 2001. View at Google Scholar · View at Scopus
  137. M. Tschop, C. Weyer, P. A. Tataranni, V. Devanarayan, E. Ravussin, and M. L. Heiman, “Circulating ghrelin levels are decreased in human obesity,” Diabetes, vol. 50, no. 4, pp. 707–709, 2001. View at Google Scholar · View at Scopus
  138. A. Katsuki, H. Urakawa, E. C. Gabazza et al., “Circulating levels of active ghrelin is associated with abdominal adiposity, hyperinsulinemia and insulin resistance in patients with type 2 diabetes mellitus,” European Journal of Endocrinology, vol. 151, no. 5, pp. 573–577, 2004. View at Publisher · View at Google Scholar · View at Scopus
  139. R. Kelishadi, M. Hashemipour, N. Mohammadifard, H. Alikhassy, and K. Adeli, “Short- and long-term relationships of serum ghrelin with changes in body composition and the metabolic syndrome in prepubescent obese children following two different weight loss programmes,” Clinical Endocrinology, vol. 69, no. 5, pp. 721–729, 2008. View at Publisher · View at Google Scholar · View at Scopus
  140. C.-C. Lee, R.-P. Lee, Y.-M. Subeq, C.-H. Wang, T.-C. Fang, and B.-G. Hsu, “Fasting serum total ghrelin level inversely correlates with metabolic syndrome in hemodialysis patients,” Archives of Medical Research, vol. 39, no. 8, pp. 785–790, 2008. View at Publisher · View at Google Scholar · View at Scopus
  141. E. Nakagawa, N. Nagaya, H. Okumura et al., “Hyperglycaemia suppresses the secretion of ghrelin, a novel growth-hormone-releasing peptide: responses to the intravenous and oral administration of glucose,” Clinical Science, vol. 103, no. 3, pp. 325–328, 2002. View at Google Scholar · View at Scopus
  142. C. Gauna, P. Uitterlinden, P. Kramer et al., “Intravenous glucose administration in fasting rats has differential effects on acylated and unacylated ghrelin in the portal and systemic circulation: a comparison between portal and peripheral concentrations in anesthetized rats,” Endocrinology, vol. 148, no. 11, pp. 5278–5287, 2007. View at Publisher · View at Google Scholar · View at Scopus
  143. P. Lucidi, G. Murdolo, C. Di Loreto et al., “Ghrelin is not necessary for adequate hormonal counterregulation of insulin-induced hypoglycemia,” Diabetes, vol. 51, no. 10, pp. 2911–2914, 2002. View at Google Scholar · View at Scopus
  144. B. B. Genís, M. L. Granada, N. Alonso et al., “Ghrelin, glucose homeostasis, and carotid intima media thickness in kidney transplantation,” Transplantation, vol. 84, no. 10, pp. 1248–1254, 2007. View at Publisher · View at Google Scholar · View at Scopus
  145. G. Xu, Y. Li, W. An et al., “Gastric mammalian target of rapamycin signaling regulates ghrelin production and food intake,” Endocrinology, vol. 150, no. 8, pp. 3637–3644, 2009. View at Publisher · View at Google Scholar · View at Scopus
  146. D. E. Cummings, J. Q. Purnell, R. S. Frayo, K. Schmidova, B. E. Wisse, and D. S. Weigle, “A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans,” Diabetes, vol. 50, no. 8, pp. 1714–1719, 2001. View at Google Scholar · View at Scopus
  147. K. E. Foster-Schubert, J. Overduin, C. E. Prudom et al., “Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates,” The Journal of Clinical Endocrinology & Metabolism, vol. 93, no. 5, pp. 1971–1979, 2008. View at Publisher · View at Google Scholar · View at Scopus
  148. K. Takachi, Y. Doki, O. Ishikawa et al., “Postoperative ghrelin levels and delayed recovery from body weight loss after distal or total gastrectomy,” Journal of Surgical Research, vol. 130, no. 1, pp. 1–7, 2006. View at Publisher · View at Google Scholar · View at Scopus
  149. R. Nass, L. S. Farhy, J. Liu et al., “Evidence for acyl-ghrelin modulation of growth hormone release in the fed state,” The Journal of Clinical Endocrinology & Metabolism, vol. 93, no. 5, pp. 1988–1994, 2008. View at Publisher · View at Google Scholar · View at Scopus
  150. D. H. St-Pierre, R. Rabasa-Lhoret, M.-E. Lavoie et al., “Fiber intake predicts ghrelin levels in overweight and obese postmenopausal women,” European Journal of Endocrinology, vol. 161, no. 1, pp. 65–72, 2009. View at Publisher · View at Google Scholar · View at Scopus
  151. S. Bellone, N. Castellino, F. Broglio et al., “Ghrelin secretion in childhood is refractory to the inhibitory effect of feeding,” The Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 4, pp. 1662–1665, 2004. View at Publisher · View at Google Scholar · View at Scopus
  152. A. Gambineri, U. Pagotto, M. Tschöp et al., “Anti-androgen treatment increases circulating ghrelin levels in obese women with polycystic ovary syndrome,” Journal of Endocrinological Investigation, vol. 26, no. 7, pp. 629–634, 2003. View at Google Scholar · View at Scopus
  153. T. M. Barber, F. F. Casanueva, F. Karpe et al., “Ghrelin levels are suppressed and show a blunted response to oral glucose in women with polycystic ovary syndrome,” European Journal of Endocrinology, vol. 158, no. 4, pp. 511–516, 2008. View at Publisher · View at Google Scholar · View at Scopus
  154. K. A. Brownley, K. C. Light, K. M. Grewen, E. E. Bragdon, A. L. Hinderliter, and S. G. West, “Postprandial ghrelin is elevated in black compared with white women,” The Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 9, pp. 4457–4463, 2004. View at Publisher · View at Google Scholar · View at Scopus
  155. J. D. Veldhuis, D. M. Keenan, and S. M. Pincus, “Motivations and methods for analyzing pulsatile hormone secretion,” Endocrine Reviews, vol. 29, no. 7, pp. 823–864, 2008. View at Publisher · View at Google Scholar · View at Scopus
  156. N. J. Beaumont, V. O. Skinner, T. M. Tan et al., “Ghrelin can bind to a species of high density lipoprotein associated with paraoxonase,” Journal of Biological Chemistry, vol. 278, no. 11, pp. 8877–8880, 2003. View at Publisher · View at Google Scholar · View at Scopus
  157. W. A. Banks, B. O. Burney, and S. M. Robinson, “Effects of triglycerides, obesity, and starvation on ghrelin transport across the blood-brain barrier,” Peptides, vol. 29, no. 11, pp. 2061–2065, 2008. View at Publisher · View at Google Scholar · View at Scopus
  158. B. Holst, A. Cygankiewicz, T. H. Jensen, M. Ankersen, and T. W. Schwartz, “High constitutive signaling of the ghrelin receptor—identification of a potent inverse agonist,” Molecular Endocrinology, vol. 17, no. 11, pp. 2201–2210, 2003. View at Publisher · View at Google Scholar · View at Scopus
  159. B. Holst, N. D. Holliday, A. Bach, C. E. Elling, H. M. Cox, and T. W. Schwartz, “Common structural basis for constitutive activity of the ghrelin receptor family,” Journal of Biological Chemistry, vol. 279, no. 51, pp. 53806–53817, 2004. View at Publisher · View at Google Scholar · View at Scopus
  160. B. Holst, E. Brandt, A. Bach, A. Heding, and T. W. Schwartz, “Nonpeptide and peptide growth hormone secretagogues act both as ghrelin receptor agonist and as positive or negative allosteric modulators of ghrelin signaling,” Molecular Endocrinology, vol. 19, no. 9, pp. 2400–2411, 2005. View at Publisher · View at Google Scholar · View at Scopus
  161. G. L. Fraser, H. R. Hoveyda, and G. S. Tannenbaum, “Pharmacological demarcation of the growth hormone, gut motility and feeding effects of ghrelin using a novel ghrelin receptor agonist,” Endocrinology, vol. 149, no. 12, pp. 6280–6288, 2008. View at Publisher · View at Google Scholar · View at Scopus
  162. B. Holst, J. Mokrosinski, M. Lang et al., “Identification of an efficacy switch region in the ghrelin receptor responsible for interchange between agonism and inverse agonism,” Journal of Biological Chemistry, vol. 282, no. 21, pp. 15799–15811, 2007. View at Publisher · View at Google Scholar · View at Scopus
  163. F. Cordido, M. L. Isidro, R. Nemiña, and S. Sangiao-Alvarellos, “Ghrelin and growth hormone secretagogues, physiological and pharmacological aspect,” Current Drug Discovery Technologies, vol. 6, no. 1, pp. 34–42, 2009. View at Publisher · View at Google Scholar · View at Scopus
  164. A. V. Mayorov, N. Amara, J. Y. Chang et al., “Catalytic antibody degradation of ghrelin increases whole-body metabolic rate and reduces refeeding in fasting mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 45, pp. 17487–17492, 2008. View at Publisher · View at Google Scholar · View at Scopus
  165. Y. Shuto, T. Shibasaki, A. Otagiri et al., “Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity,” Journal of Clinical Investigation, vol. 109, no. 11, pp. 1429–1436, 2002. View at Publisher · View at Google Scholar · View at Scopus
  166. Y. Sun, N. F. Butte, J. M. Garcia, and R. G. Smith, “Characterization of adult ghrelin and ghrelin receptor knockout mice under positive and negative energy balance,” Endocrinology, vol. 149, no. 2, pp. 843–850, 2008. View at Publisher · View at Google Scholar · View at Scopus
  167. J. M. Zigman, Y. Nakano, R. Coppari et al., “Mice lacking ghrelin receptors resist the development of diet-induced obesity,” Journal of Clinical Investigation, vol. 115, no. 12, pp. 3564–3572, 2005. View at Publisher · View at Google Scholar · View at Scopus
  168. L. P. Shearman, S.-P. Wang, S. Helmling et al., “Ghrelin neutralization by a ribonucleic acid-SPM ameliorates obesity in diet-induced obese mice,” Endocrinology, vol. 147, no. 3, pp. 1517–1526, 2006. View at Publisher · View at Google Scholar · View at Scopus
  169. P. T. Pfluger, H. Kirchner, S. Günnel et al., “Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure,” American Journal of Physiology, vol. 294, no. 3, pp. G610–G618, 2008. View at Publisher · View at Google Scholar · View at Scopus
  170. G. A. Bewick, A. Kent, D. Campbell et al., “Mice with hyperghrelinemia are hyperphagic and glucose intolerant and have reduced leptin sensitivity,” Diabetes, vol. 58, no. 4, pp. 840–846, 2009. View at Publisher · View at Google Scholar · View at Scopus
  171. C. Theander-Carrillo, P. Wiedmer, P. Cettour-Rose et al., “Ghrelin action in the brain controls adipocyte metabolism,” Journal of Clinical Investigation, vol. 116, no. 7, pp. 1983–1993, 2006. View at Publisher · View at Google Scholar · View at Scopus
  172. E. P. Zorrilla, S. Iwasaki, J. A. Moss et al., “Vaccination against weight gain,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 35, pp. 13226–13231, 2006. View at Publisher · View at Google Scholar · View at Scopus
  173. K. E. Wortley, J.-P. Del Rincon, J. D. Murray et al., “Absence of ghrelin protects against early-onset obesity,” Journal of Clinical Investigation, vol. 115, no. 12, pp. 3573–3578, 2005. View at Publisher · View at Google Scholar · View at Scopus
  174. Y. Sun, S. Ahmed, and R. G. Smith, “Deletion of ghrelin impairs neither growth nor appetite,” Molecular and Cellular Biology, vol. 23, no. 22, pp. 7973–7981, 2003. View at Publisher · View at Google Scholar · View at Scopus
  175. C. R. Cruz and R. G. Smith, “The growth hormone secretagogue receptor,” Vitamins & Hormones, vol. 77, pp. 47–88, 2007. View at Publisher · View at Google Scholar · View at Scopus
  176. J. A. Vizcarra, J. D. Kirby, S. K. Kim, and M. L. Galyean, “Active immunization against ghrelin decreases weight gain and alters plasma concentrations of growth hormone in growing pigs,” Domestic Animal Endocrinology, vol. 33, no. 2, pp. 176–189, 2007. View at Publisher · View at Google Scholar · View at Scopus
  177. Y. Sun, P. Wang, H. Zheng, and R. G. Smith, “Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 13, pp. 4679–4684, 2004. View at Publisher · View at Google Scholar · View at Scopus
  178. P. J. Wellman, C. N. Hollas, and A. E. Elliott, “Systemic ghrelin sensitizes cocaine-induced hyperlocomotion in rats,” Regulatory Peptides, vol. 146, no. 1–3, pp. 33–37, 2008. View at Publisher · View at Google Scholar · View at Scopus
  179. K. E. Wortley, K. D. Anderson, K. Garcia et al., “Genetic deletion of ghrelin does decrease food intake but influences metabolic fuel preference,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 21, pp. 8227–8232, 2004. View at Publisher · View at Google Scholar · View at Scopus
  180. S. Helmling, C. Maasch, D. Eulberg et al., “Inhibition of ghrelin action in vitro and in vivo by an RNA-Spiegelmer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 36, pp. 13174–13179, 2004. View at Publisher · View at Google Scholar · View at Scopus
  181. P. Zizzari, H. Halem, J. Taylor et al., “Endogenous ghrelin regulates episodic GH secretion by amplifying GH pulse amplitude: evidence from antagonism of the GHS-R1a receptor,” Endocrinology, vol. 146, no. 9, pp. 3836–3842, 2005. View at Publisher · View at Google Scholar · View at Scopus
  182. N. Salomé, C. Hansson, M. Taube et al., “On the central mechanism underlying ghrelin's chronic pro-obesity effects in rats: new insights from studies exploiting a potent ghrelin receptor antagonist,” Journal of Neuroendocrinology, vol. 21, no. 9, pp. 777–785, 2009. View at Publisher · View at Google Scholar · View at Scopus
  183. M. A. Vlasova, K. Järvinen, and K.-H. Herzig, “Cardiovascular effects of ghrelin antagonist in conscious rats,” Regulatory Peptides, vol. 156, no. 1–3, pp. 72–76, 2009. View at Publisher · View at Google Scholar · View at Scopus
  184. A. Asakawa, A. Inui, T. Kaga et al., “Antagonism of ghrelin receptor reduces food intake and body weight gain in mice,” Gut, vol. 52, no. 7, pp. 947–952, 2003. View at Publisher · View at Google Scholar · View at Scopus
  185. W. P. Esler, J. Rudolph, T. H. Claus et al., “Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss,” Endocrinology, vol. 148, no. 11, pp. 5175–5185, 2007. View at Publisher · View at Google Scholar · View at Scopus
  186. R. Nogueiras, M. López, R. Lage et al., “Bsx, a novel hypothalamic factor linking feeding with locomotor activity, is regulated by energy availability,” Endocrinology, vol. 149, no. 6, pp. 3009–3015, 2008. View at Publisher · View at Google Scholar · View at Scopus
  187. S. Petersenn, A. C. Rasch, M. Penshorn, F. U. Beil, and H. M. Schulte, “Genomic structure and transcriptional regulation of the human growth hormone secretagogue receptor,” Endocrinology, vol. 142, no. 6, pp. 2649–2659, 2001. View at Publisher · View at Google Scholar · View at Scopus
  188. I. Bulgarelli, L. Tamiazzo, E. Bresciani et al., “Desacyl-ghrelin and synthetic GH-secretagogues modulate the production of inflammatory cytokines in mouse microglia cells stimulated by ß-amyloid fibrils,” Journal of Neuroscience Research, vol. 87, no. 12, pp. 2718–2727, 2009. View at Publisher · View at Google Scholar · View at Scopus
  189. M. Fujimiya, A. Asakawa, K. Ataka, I. Kato, and A. Inui, “Different effects of ghrelin, des-acyl ghrelin and obestatin on gastroduodenal motility in conscious rats,” World Journal of Gastroenterology, vol. 14, no. 41, pp. 6318–6326, 2008. View at Publisher · View at Google Scholar · View at Scopus
  190. T. Inhoff, H. Mönnikes, S. Noetzel et al., “Desacyl ghrelin inhibits the orexigenic effect of peripherally injected ghrelin in rats,” Peptides, vol. 29, no. 12, pp. 2159–2168, 2008. View at Publisher · View at Google Scholar · View at Scopus
  191. A. Giovambattista, R. C. Gaillard, and E. Spinedi, “Ghrelin gene-related peptides modulate rat white adiposity,” Vitamins & Hormones, vol. 77, pp. 171–205, 2007. View at Publisher · View at Google Scholar · View at Scopus
  192. M. Muscaritoli, A. Molfino, M. G. Chiappini et al., “Anorexia in hemodialysis patients: the possible role of des-acyl ghrelin,” American Journal of Nephrology, vol. 27, no. 4, pp. 360–365, 2007. View at Publisher · View at Google Scholar · View at Scopus
  193. N. Filigheddu, V. F. Gnocchi, M. Coscia et al., “Ghrelin and des-acyl ghrelin promote differentiation and fusion of C2C12 skeletal muscle cells,” Molecular Biology of the Cell, vol. 18, no. 3, pp. 986–994, 2007. View at Publisher · View at Google Scholar · View at Scopus
  194. L. Li, L.-K. Zhang, Y.-Z. Pang et al., “Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats,” Acta Pharmacologica Sinica, vol. 27, no. 5, pp. 527–535, 2006. View at Publisher · View at Google Scholar · View at Scopus
  195. A. D. Patel, S. A. Stanley, K. G. Murphy et al., “Ghrelin stimulates insulin-induced glucose uptake in adipocytes,” Regulatory Peptides, vol. 134, no. 1, pp. 17–22, 2006. View at Publisher · View at Google Scholar · View at Scopus
  196. C. Y. Chen, Y. Chao, F. Y. Chang, E. J. Chien, S. D. Lee, and M. L. Doong, “Intracisternal des-acyl ghrelin inhibits food intake and non-nutrient gastric emptying in conscious rats,” International Journal of Molecular Medicine, vol. 16, no. 4, pp. 695–699, 2005. View at Google Scholar · View at Scopus
  197. Y. Tsubota, K. Owada-Makabe, K. Yukawa, and M. Maeda, “Hypotensive effect of des-acyl ghrelin at nucleus tractus solitarii of rat,” NeuroReport, vol. 16, no. 2, pp. 163–166, 2005. View at Publisher · View at Google Scholar · View at Scopus
  198. C. Gauna, P. J. D. Delhanty, L. J. Hofland et al., “Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes,” The Journal of Clinical Endocrinology & Metabolism, vol. 90, no. 2, pp. 1055–1060, 2005. View at Publisher · View at Google Scholar · View at Scopus
  199. G. Muccioli, N. Pons, C. Ghe, F. Catapano, R. Granata, and E. Ghigo, “Ghrelin and des-acyl ghrelin both inhibit isoproterenol-induced lipolysis in rat adipocytes via a non-type 1a growth hormone secretagogue receptor,” European Journal of Pharmacology, vol. 498, no. 1–3, pp. 27–35, 2004. View at Publisher · View at Google Scholar · View at Scopus
  200. W. G. Li, D. Gavrila, X. Liu et al., “Ghrelin inhibits proinflammatory responses and nuclear factor-?B activation in human endothelial cells,” Circulation, vol. 109, no. 18, pp. 2221–2226, 2004. View at Publisher · View at Google Scholar · View at Scopus
  201. I. Bedendi, G. Alloatti, A. Marcantoni et al., “Cardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln14-ghrelin,” European Journal of Pharmacology, vol. 476, no. 1-2, pp. 87–95, 2003. View at Publisher · View at Google Scholar · View at Scopus
  202. H. A. Halem, J. E. Taylor, J. Z. Dong et al., “A novel growth hormone secretagogue-1a receptor antagonist that blocks ghrelin-induced growth hormone secretion but induces increased body weight gain,” Neuroendocrinology, vol. 81, no. 5, pp. 339–349, 2005. View at Publisher · View at Google Scholar · View at Scopus
  203. B. Holst, M. Lang, E. Brandt et al., “Ghrelin receptor inverse agonists: identification of an active peptide core and its interaction epitopes on the receptor,” Molecular Pharmacology, vol. 70, no. 3, pp. 936–946, 2006. View at Publisher · View at Google Scholar · View at Scopus
  204. A. Moulin, L. Demange, G. Bergé et al., “Toward potent ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure. 2. Synthesis and pharmacological in vitro and in vivo evaluations,” Journal of Medicinal Chemistry, vol. 50, no. 23, pp. 5790–5806, 2007. View at Publisher · View at Google Scholar · View at Scopus
  205. J. Rudolph, W. P. Esler, S. O'Connor et al., “Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity,” Journal of Medicinal Chemistry, vol. 50, no. 21, pp. 5202–5216, 2007. View at Publisher · View at Google Scholar · View at Scopus
  206. L. Demange, D. Boeglin, A. Moulin et al., “Synthesis and pharmacological in vitro and in vivo evaluations of novel triazole derivatives as ligands of the ghrelin receptor. 1,” Journal of Medicinal Chemistry, vol. 50, no. 8, pp. 1939–1957, 2007. View at Publisher · View at Google Scholar · View at Scopus
  207. G. Muccioli, A. Baragli, R. Granata, M. Papotti, and E. Ghigo, “Heterogeneity of ghrelin/growth hormone secretagogue receptors: toward the understanding of the molecular identity of novel ghrelin/GHS receptors,” Neuroendocrinology, vol. 86, no. 3, pp. 147–164, 2007. View at Publisher · View at Google Scholar · View at Scopus
  208. C.-Y. Chen, A. Inui, A. Asakawa et al., “Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats,” Gastroenterology, vol. 129, no. 1, pp. 8–25, 2005. View at Publisher · View at Google Scholar · View at Scopus
  209. E. Jerlhag, E. Egecioglu, S. L. Dickson, A. Douhan, L. Svensson, and J. A. Engel, “Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbens,” Addiction Biology, vol. 12, no. 1, pp. 6–16, 2007. View at Publisher · View at Google Scholar · View at Scopus
  210. C. Gauna, F. M. Meyler, J. A. Janssen et al., “Administration of acylated ghrelin reduces insulin sensitivity, whereas the combination of acylated plus unacylated ghrelin strongly improves insulin sensitivity,” The Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 10, pp. 5035–5042, 2004. View at Publisher · View at Google Scholar · View at Scopus
  211. I. Johansson, S. Destefanis, N. D. Aberg et al., “Proliferative and protective effects of growth hormone secretagogues on adult rat hippocampal progenitor cells,” Endocrinology, vol. 149, no. 5, pp. 2191–2199, 2008. View at Publisher · View at Google Scholar · View at Scopus
  212. M. Sato, K. Nakahara, S. Goto et al., “Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord,” Biochemical and Biophysical Research Communications, vol. 350, no. 3, pp. 598–603, 2006. View at Publisher · View at Google Scholar · View at Scopus
  213. W. Zhang, Y. Hu, T. R. Lin, Y. Fan, and M. W. Mulholland, “Stimulation of neurogenesis in rat nucleus of the solitary tract by ghrelin,” Peptides, vol. 26, no. 11, pp. 2280–2288, 2005. View at Publisher · View at Google Scholar · View at Scopus
  214. W. Zhang, T. R. Lin, Y. Hu et al., “Ghrelin stimulates neurogenesis in the dorsal motor nucleus of the vagus,” Journal of Physiology, vol. 559, no. 3, pp. 729–737, 2004. View at Publisher · View at Google Scholar · View at Scopus
  215. T. Hayashida, K. Murakami, K. Mogi et al., “Ghrelin in domestic animals: distribution in stomach and its possible role,” Domestic Animal Endocrinology, vol. 21, no. 1, pp. 17–24, 2001. View at Publisher · View at Google Scholar · View at Scopus
  216. R. D. Kineman and R. M. Luque, “Evidence that ghrelin is as potent as growth hormone (GH)-releasing hormone (GHRH) in releasing GH from primary pituitary cell cultures of a nonhuman primate (Papio anubis), acting through intracellular signaling pathways distinct from GHRH,” Endocrinology, vol. 148, no. 9, pp. 4440–4449, 2007. View at Publisher · View at Google Scholar · View at Scopus
  217. A. Glavaski-Joksimovic, K. Jeftinija, C. G. Scanes, L. L. Anderson, and S. Jeftinija, “Stimulatory effect of ghrelin on isolated porcine somatotropes,” Neuroendocrinology, vol. 77, no. 6, pp. 367–379, 2003. View at Publisher · View at Google Scholar · View at Scopus
  218. S. Ahmed and S. Harvey, “Ghrelin: a hypothalamic GH-releasing factor in domestic fowl (Gallus domesticus),” Journal of Endocrinology, vol. 172, no. 1, pp. 117–125, 2002. View at Publisher · View at Google Scholar · View at Scopus
  219. M. A. Shupnik, “Regulational effect of ghrelin on growth hormone secretion from perifused rat anterior pituitary cells,” Journal of Neuroendocrinology, vol. 14, no. 2, pp. 156–162, 2002. View at Publisher · View at Google Scholar · View at Scopus
  220. F. Broglio, A. Benso, C. Gottero et al., “Non-acylated ghrelin does not possess the pituitaric and pancreatic endocrine activity of acylated ghrelin in humans,” Journal of Endocrinological Investigation, vol. 26, no. 3, pp. 192–196, 2003. View at Google Scholar · View at Scopus
  221. F. Broglio, C. Gottero, F. Prodam et al., “Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans,” The Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 6, pp. 3062–3065, 2004. View at Publisher · View at Google Scholar · View at Scopus
  222. J. Nagamine, R. Nagata, H. Seki et al., “Pharmacological profile of a new orally active growth hormone secretagogue, SM-130686,” Journal of Endocrinology, vol. 171, no. 3, pp. 481–489, 2001. View at Publisher · View at Google Scholar · View at Scopus
  223. B. S. Hansen, K. Raun, K. K. Nielsen et al., “Pharmacological characterisation of a new oral GH secretagogue, NN703,” European Journal of Endocrinology, vol. 141, no. 2, pp. 180–189, 1999. View at Publisher · View at Google Scholar · View at Scopus
  224. J. M. Garcia and W. J. Polvino, “Pharmacodynamic hormonal effects of anamorelin, a novel oral ghrelin mimetic and growth hormone secretagogue in healthy volunteers,” Growth Hormone and IGF Research, vol. 19, no. 3, pp. 267–273, 2009. View at Publisher · View at Google Scholar · View at Scopus
  225. K. Matsuda, T. Miura, H. Kaiya et al., “Regulation of food intake by acyl and des-acyl ghrelins in the goldfish,” Peptides, vol. 27, no. 9, pp. 2321–2325, 2006. View at Publisher · View at Google Scholar · View at Scopus
  226. S. L. Kaplan, M. M. Grumbach, and M. L. Aubert, “The ontogenesis of pituitary hormones and hypothalamic factors in the human fetus: maturation of central nervous system regulation of anterior pituitary function,” Recent Progress in Hormone Research, vol. 32, pp. 161–243, 1976. View at Google Scholar · View at Scopus
  227. M. Yan, M. Hernandez, R. Xu, and C. Chen, “Effect of GHRH and GHRP-2 treatment in vitro on GH secretion and levels of GH, pituitary transcription factor-1, GHRH-receptor, GH-secretagogue-receptor and somatostatin receptor mRNAs in ovine pituitary cells,” European Journal of Endocrinology, vol. 150, no. 2, pp. 235–242, 2004. View at Publisher · View at Google Scholar · View at Scopus
  228. X. Li, J. He, W. Hu, and Z. Yin, “The essential role of endogenous ghrelin in growth hormone expression during zebrafish adenohypophysis development,” Endocrinology, vol. 150, no. 6, pp. 2767–2774, 2009. View at Publisher · View at Google Scholar · View at Scopus
  229. A. Torsello, M. Luoni, R. Grilli et al., “Hexarelin stimulation of growth hormone release and mRNA levels in an infant and adult rat model of impaired GHRH function,” Neuroendocrinology, vol. 65, no. 2, pp. 91–97, 1997. View at Google Scholar · View at Scopus
  230. A. R. T. Bailey, M. E. Giles, C. H. Brown et al., “Chronic central infusion of growth hormone secretagogues: effects on Fos expression and peptide gene expression in the rat arcuate nucleus,” Neuroendocrinology, vol. 70, no. 2, pp. 83–92, 1999. View at Publisher · View at Google Scholar · View at Scopus
  231. M. S. Mondal, Y. Date, H. Yamaguchi et al., “Identification of ghrelin and its receptor in neurons of the rat arcuate nucleus,” Regulatory Peptides, vol. 126, no. 1-2, pp. 55–59, 2005. View at Publisher · View at Google Scholar · View at Scopus
  232. M. A. Cowley, R. G. Smith, S. Diano et al., “The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis,” Neuron, vol. 37, no. 4, pp. 649–661, 2003. View at Publisher · View at Google Scholar · View at Scopus
  233. S. Lu, J.-L. Guan, Q.-P. Wang et al., “Immunocytochemical observation of ghrelin-containing neurons in the rat arcuate nucleus,” Neuroscience Letters, vol. 321, no. 3, pp. 157–160, 2002. View at Publisher · View at Google Scholar · View at Scopus
  234. P. J. Currie, A. Mirza, R. Fuld, D. Park, and J. R. Vasselli, “Ghrelin is an orexigenic and metabolic signaling peptide in the arcuate and paraventricular nuclei,” American Journal of Physiology, vol. 289, no. 2, pp. R353–R358, 2005. View at Publisher · View at Google Scholar · View at Scopus
  235. Y. Hori, H. Kageyama, J.-L. Guan et al., “Synaptic interaction between ghrelin- and ghrelin-containing neurons in the rat hypothalamus,” Regulatory Peptides, vol. 145, no. 1–3, pp. 122–127, 2008. View at Publisher · View at Google Scholar · View at Scopus
  236. A. Mano-Otagiri, T. Nemoto, A. Sekino et al., “Growth hormone-releasing hormone (GHRH) neurons in the arcuate nucleus (Arc) of the hypothalamus are decreased in transgenic rats whose expression of ghrelin receptor is attenuated: evidence that ghrelin receptor is involved in the up-regulation of GHRH expression in the ARC,” Endocrinology, vol. 147, no. 9, pp. 4093–4103, 2006. View at Publisher · View at Google Scholar · View at Scopus
  237. T. P. Fletcher, G. B. Thomas, and I. J. Clarke, “Growth hormone-releasing hormone and somatostatin concentrations in the hypophysial portal blood of conscious sheep during the infusion of growth hormone-releasing peptide-6,” Domestic Animal Endocrinology, vol. 13, no. 3, pp. 251–258, 1996. View at Google Scholar · View at Scopus
  238. A. M. Wren, C. J. Small, C. V. Fribbens et al., “The hypothalamic mechanisms of the hypophysiotropic action of ghrelin,” Neuroendocrinology, vol. 76, no. 5, pp. 316–324, 2002. View at Publisher · View at Google Scholar · View at Scopus
  239. M. Alba, D. Fintini, C. Y. Bowers, A. F. Parlow, and R. Salvatori, “Effects of long-term treatment with growth hormone-releasing peptide-2 in the GHRH knockout mouse,” American Journal of Physiology, vol. 289, no. 5, pp. E762–E767, 2005. View at Publisher · View at Google Scholar · View at Scopus
  240. S.-G. Roh, C. Chen, K.-C. Choi, Y. Shrestha, and S.-I. Sasaki, “Is GHRH receptor essential to GHRP-2-induced GH secretion in primary cultured rat pituitary cells?” Endocrinology, vol. 143, no. 5, pp. 1964–1967, 2002. View at Publisher · View at Google Scholar · View at Scopus
  241. F. Roelfsema, N. R. Biermasz, R. G. Veldman et al., “Growth hormone (GH) secretion in patients with an inactivating defect of the GH-releasing hormone (GHRH) receptor is pulsatile: evidence for a role for non-GHRH inputs into the generation of GH pulses,” The Journal of Clinical Endocrinology & Metabolism, vol. 86, no. 6, pp. 2459–2464, 2001. View at Publisher · View at Google Scholar · View at Scopus
  242. V. Popovic, S. Damjanovic, D. Micic, M. Djurovic, C. Dieguez, and F. F. Casanueva, “Blocked growth hormone-releasing peptide (GHRP-6)-induced GH secretion and absence of the synergic action of GHRP-6 plus GH-releasing hormone in patients with hypothalamopituitary disconnection: evidence that GHRP-6 main action is exerted at the hypothalamic level,” The Journal of Clinical Endocrinology & Metabolism, vol. 80, no. 3, pp. 942–947, 1995. View at Google Scholar · View at Scopus
  243. D. Fintini, M. Alba, A. V. Schally, C. Y. Bowers, A. F. Parlow, and R. Salvatori, “Effects of combined long-term treatment with a growth hormone-releasing hormone analogue and a growth hormone secretagogue in the growth hormone-releasing hormone knock out mouse,” Neuroendocrinology, vol. 82, no. 3-4, pp. 198–207, 2005. View at Publisher · View at Google Scholar · View at Scopus
  244. S. L. Dickson, O. Doutrelant-Viltart, and G. Leng, “GH-deficient dw/dw rats and lit/lit mice show increased Fos expression in the hypothalamic arcuate nucleus following systemic injection of GH-releasing peptide-6,” Journal of Endocrinology, vol. 146, no. 3, pp. 519–526, 1995. View at Google Scholar · View at Scopus
  245. M. Maghnie, M. C. Pennati, E. Civardi et al., “GH response to ghrelin in subjects with congenital GH deficiency: evidence that ghrelin action requires hypothalamic-pituitary connections,” European Journal of Endocrinology, vol. 156, no. 4, pp. 449–454, 2007. View at Publisher · View at Google Scholar · View at Scopus
  246. H. G. Maheshwari, A. Rahim, S. M. Shalet, and G. Baumann, “Selective lack of growth hormone (GH) response to the GH-releasing peptide hexarelin in patients with GH-releasing hormone receptor deficiency,” The Journal of Clinical Endocrinology & Metabolism, vol. 84, no. 3, pp. 956–959, 1999. View at Google Scholar · View at Scopus
  247. N. Pandya, R. DeMott-Friberg, C. Y. Bowers, A. L. Barkan, and C. A. Jaffe, “Growth hormone (GH)-releasing peptide-6 requires endogenous hypothalamic GH-releasing hormone for maximal GH stimulation,” The Journal of Clinical Endocrinology & Metabolism, vol. 83, no. 4, pp. 1186–1189, 1998. View at Publisher · View at Google Scholar · View at Scopus
  248. G. J. Hickey, J. Drisko, T. Faidley et al., “Mediation by the central nervous system is critical to the in vivo activity of the GH secretagogue L-692,585,” Journal of Endocrinology, vol. 148, no. 2, pp. 371–380, 1996. View at Google Scholar · View at Scopus
  249. H. ThidarMyint, H. Yoshida, T. Ito, M. He, H. Inoue, and H. Kuwayama, “Combined administration of ghrelin and GHRH synergistically stimulates GH release in Holstein preweaning calves,” Domestic Animal Endocrinology, vol. 34, no. 1, pp. 118–123, 2008. View at Publisher · View at Google Scholar · View at Scopus
  250. C. Y. Bowers, B. Laferrere, D. L. Hurley, and J. D. Veldhuis, “The role of growth hormone and ghrelin in feeding and body composition,” in Energy Metabolism and Obesity: Research and Clinical Applications, P. A. Donahoe, Ed., pp. 125–154, The Humana Press, Totowa, NJ, USA, 2008. View at Google Scholar
  251. E. Arvat, M. Maccario, L. Di Vito et al., “Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone,” The Journal of Clinical Endocrinology & Metabolism, vol. 86, no. 3, pp. 1169–1174, 2001. View at Publisher · View at Google Scholar · View at Scopus
  252. C. Y. Bowers, G. A. Reynolds, D. Durham, C. M. Barrera, S. S. Pezzoli, and M. O. Thorner, “Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone,” The Journal of Clinical Endocrinology & Metabolism, vol. 70, no. 4, pp. 975–982, 1990. View at Google Scholar · View at Scopus
  253. C. Y. Bowers and R. Granda-Ayala, “Growth hormone/insulin-like growth factor-1 response to acute and chronic growth hormone-releasing peptide-2, growth hormone-releasing hormone 1-44NH2 and in combination in older men and women with decreased growth hormone secretion,” Endocrine, vol. 14, no. 1, pp. 79–86, 2001. View at Google Scholar · View at Scopus
  254. Y. Hataya, T. Akamizu, K. Takaya et al., “A low dose of ghrelin stimulates growth hormone (GH) release synergistically with GH-releasing hormone in humans,” The Journal of Clinical Endocrinology & Metabolism, vol. 86, no. 9, pp. 4552–4555, 2001. View at Publisher · View at Google Scholar · View at Scopus
  255. C. Y. Bowers, F. A. Momany, G. A. Reynolds, and A. Hong, “On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone,” Endocrinology, vol. 114, no. 5, pp. 1537–1545, 1984. View at Google Scholar · View at Scopus
  256. M. Rico, V. Rueda, M. T. Lorenzo, A. Núñez, and L. F. De la Cruz, “Effect of growth hormone-releasing peptide 1–6 on GH secretion-stimulated by GHRH and pyridostigmine in lambs,” Journal of Physiology and Biochemistry, vol. 54, no. 2, pp. 67–76, 1998. View at Google Scholar · View at Scopus
  257. C. Y. Bowers, K. Veeraragavan, and K. Sethumadhavan, “Atypical growth hormone releasing peptides,” in Growth Hormone. II. Basic and Clinical Aspects, B. B. Bercu and R. F. Walker, Eds., pp. 203–222, Springer, New York, NY, USA, 1994. View at Google Scholar
  258. T. Wells, D. M. Flavell, S. E. Wells, D. F. Carmignac, and I. C. A. F. Robinson, “Effects of growth hormone secretagogues in the transgenic growth-retarded (Tgr) rat,” Endocrinology, vol. 138, no. 2, pp. 580–587, 1997. View at Publisher · View at Google Scholar · View at Scopus
  259. L. Jimenez-Reina, R. Canete, M. J. de la Torre, and G. Bernal, “Influence of chronic treatment with the growth hormone secretagogue Ipamorelin, in young female rats: somatotroph response in vitro,” Histology and Histopathology, vol. 17, no. 3, pp. 707–714, 2002. View at Google Scholar · View at Scopus
  260. D. L. Russell-Jones and M. Umpleby, “Protein anabolic action of insulin, growth hormone and insulin-like growth factor I,” European Journal of Endocrinology, vol. 135, no. 6, pp. 631–642, 1996. View at Google Scholar · View at Scopus
  261. E. Arvat, B. Maccagno, J. Ramunni et al., “Influence of galanin and serotonin on the endocrine response to Hexarelin, a synthetic peptidyl GH-secretagogue, in normal women,” Journal of Endocrinological Investigation, vol. 21, no. 10, pp. 673–679, 1998. View at Google Scholar · View at Scopus
  262. T. M. E. Davis, J. M. Burrin, and S. R. Bloom, “Growth hormone (GH) release in response to GH-releasing hormone in man in 3-fold enhanced by galanin,” The Journal of Clinical Endocrinology & Metabolism, vol. 65, no. 6, pp. 1248–1252, 1987. View at Google Scholar · View at Scopus
  263. N. Kitajima, K. Chihara, H. Abe, Y. Okimura, and S. Shakutsui, “Galanin stimulates immunoreactive growth hormone-releasing factor secretion from rat hypothalamic slices perifused in vitro,” Life Sciences, vol. 47, no. 25, pp. 2371–2376, 1990. View at Publisher · View at Google Scholar · View at Scopus
  264. Z. Liposits, I. Merchenthaler, J. J. Reid, and A. Negro-Vilar, “Galanin-immunoreactive axons innervate somatostatin-synthesizing neurons in the anterior periventricular nucleus of the rat,” Endocrinology, vol. 132, no. 2, pp. 917–923, 1993. View at Publisher · View at Google Scholar · View at Scopus
  265. H. A. Delemarre-van De Waal, K. A. Burton, E. B. Kabigting, R. A. Steiner, and D. K. Clifton, “Expression and sexual dimorphism of galanin messenger ribonucleic acid in growth hormone-releasing hormone neurons of the rat during development,” Endocrinology, vol. 134, no. 2, pp. 665–671, 1994. View at Publisher · View at Google Scholar · View at Scopus
  266. D. M. Maiter, S. C. Hooi, J. I. Koenig, and J. B. Martin, “Galanin is a physiological regulator of spontaneous pulsatile secretion of growth hormone in the male rat,” Endocrinology, vol. 126, no. 2, pp. 1216–1222, 1990. View at Google Scholar · View at Scopus
  267. L. Cremagnani, M. Vaccari, E. Maronati et al., “Potentiating effect of galanin on GHRH-induced GH release. Comparison between old and young subjects,” Hormone and Metabolic Research, vol. 28, no. 2, pp. 101–104, 1996. View at Google Scholar · View at Scopus
  268. H. Yagi, H. Kaji, M. Sato, Y. Okimura, and K. Chihara, “Effect of intravenous or intracerebroventricular injections of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 on GH release in conscious, freely moving male rats,” Neuroendocrinology, vol. 63, no. 2, pp. 198–206, 1996. View at Google Scholar · View at Scopus
  269. I. M. Chapman, M. A. Bach, E. Van Cauter et al., “Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects,” The Journal of Clinical Endocrinology & Metabolism, vol. 81, no. 12, pp. 4249–4257, 1996. View at Publisher · View at Google Scholar · View at Scopus
  270. J. D. Veldhuis, G. A. Reynolds, A. Iranmanesh, and C. Y. Bowers, “Twenty-four hour continuous ghrelin infusion augments physiologically pulsatile, nycthemeral, and entropic (feedback-regulated) modes of growth hormone secretion,” The Journal of Clinical Endocrinology & Metabolism, vol. 93, no. 9, pp. 3597–3603, 2008. View at Publisher · View at Google Scholar · View at Scopus
  271. C. Y. Bowers, R. Granda, S. Mohan, J. Kuipers, D. Baylink, and J. D. Veldhuis, “Sustained elevation of pulsatile growth hormone (GH) secretion and insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and IGFBP-5 concentrations during 30-day continuous subcutaneous infusion of GH-releasing peptide-2 in older men and women,” The Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 5, pp. 2290–2300, 2004. View at Publisher · View at Google Scholar · View at Scopus
  272. A. Rahim, P. A. O'Neill, and S. M. Shalet, “The effect of chronic hexarelin administration on the pituitary-adrenal axis and prolactin,” Clinical Endocrinology, vol. 50, no. 1, pp. 77–84, 1999. View at Publisher · View at Google Scholar · View at Scopus
  273. R.-M. Frieboes, H. Murck, I. A. Antonijevic, and A. Steiger, “Effects of growth hormone-releasing peptide-6 on the nocturnal secretion of GH, ACTH and cortisol and on the sleep EEG in man: role of routes of administration,” Journal of Neuroendocrinology, vol. 11, no. 6, pp. 473–478, 1999. View at Publisher · View at Google Scholar · View at Scopus
  274. E. Arvat, B. Maccagno, J. Ramunni et al., “Hexarelin, a synthetic growth-hormone releasing peptide, shows no interaction with corticotropin-releasing hormone and vasopressin on adrenocorticotropin and cortisol secretion in humans,” Neuroendocrinology, vol. 66, no. 6, pp. 432–438, 1997. View at Google Scholar · View at Scopus
  275. E. Arvat, L. Di Vito, B. Maccagno et al., “Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH, prolactin, ACTH and cortisol levels in man. Comparison with the effects of GHRH, TRH and hCRH,” Peptides, vol. 18, no. 6, pp. 885–891, 1997. View at Publisher · View at Google Scholar · View at Scopus
  276. L. L. Anderson, S. Jeftinija, C. G. Scanes et al., “Physiology of ghrelin and related peptides,” Domestic Animal Endocrinology, vol. 29, no. 1, pp. 111–144, 2005. View at Publisher · View at Google Scholar · View at Scopus
  277. R.-M. Frieboes, H. Murck, P. Maier, T. Schier, F. Holsboer, and A. Steiger, “Growth hormone-releasing peptide-6 stimulates sleep, growth hormone, ACTH and cortisol release in normal man,” Neuroendocrinology, vol. 61, no. 5, pp. 584–589, 1995. View at Google Scholar · View at Scopus
  278. L. E. Johnstone, R. Srisawat, E. Kumarnsit, and G. Leng, “Hypothalamic expression of NPY mRNA, vasopressin mRNA and CRF mRNA in response to food restriction and central administration of the orexigenic peptide GHRP-6,” Stress, vol. 8, no. 1, pp. 59–67, 2005. View at Publisher · View at Google Scholar · View at Scopus
  279. P. Lucidi, G. Murdolo, C. Di Loreto et al., “Metabolic and endocrine effects of physiological increments in plasma ghrelin concentrations,” Nutrition, Metabolism and Cardiovascular Diseases, vol. 15, no. 6, pp. 410–417, 2005. View at Publisher · View at Google Scholar · View at Scopus
  280. M. Maccario, J. D. Veldhuis, F. Broglio et al., “Impact of two or three daily subcutaneous injections of hexarelin, a synthetic growth hormone (GH) secretagogue, on 24-h GH, prolactin, adrenocorticotropin and cortisol secretion in humans,” European Journal of Endocrinology, vol. 146, no. 3, pp. 310–318, 2002. View at Google Scholar · View at Scopus
  281. F. Tassone, F. Broglio, S. Destefanis et al., “Neuroendocrine and metabolic effects of acute ghrelin administration in human obesity,” The Journal of Clinical Endocrinology & Metabolism, vol. 88, no. 11, pp. 5478–5483, 2003. View at Publisher · View at Google Scholar · View at Scopus
  282. H. Yu and K. Kim, “Direct nose-to-brain transfer of a growth hormone releasing neuropeptide, hexarelin after intranasal administration to rabbits,” International Journal of Pharmaceutics, vol. 378, no. 1-2, pp. 73–79, 2009. View at Publisher · View at Google Scholar · View at Scopus
  283. A. Moulin, J. Ryan, J. Martinez, and J.-A. Fehrentz, “Recent developments in ghrelin receptor ligands,” ChemMedChem, vol. 2, no. 9, pp. 1242–1259, 2007. View at Publisher · View at Google Scholar · View at Scopus
  284. W. A. Banks, M. Tschop, S. M. Robinson, and M. L. Heiman, “Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure,” Journal of Pharmacology and Experimental Therapeutics, vol. 302, no. 2, pp. 822–827, 2002. View at Publisher · View at Google Scholar · View at Scopus
  285. G. Muccioli, M. Tschop, M. Papotti, R. Deghenghi, M. Heiman, and E. Ghigo, “Neuroendocrine and peripheral activities of ghrelin: implications in metabolism and obesity,” European Journal of Pharmacology, vol. 440, no. 2-3, pp. 235–254, 2002. View at Publisher · View at Google Scholar · View at Scopus
  286. W. Pan, H. Tu, and A. J. Kastin, “Differential BBB interactions of three ingestive peptides: obestatin, ghrelin, and adiponectin,” Peptides, vol. 27, no. 4, pp. 911–916, 2006. View at Publisher · View at Google Scholar · View at Scopus
  287. B. Klinger, A. Silbergeld, R. Deghenghi, J. Frenkel, and Z. Laron, “Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormone-releasing peptide in short children,” European Journal of Endocrinology, vol. 134, no. 6, pp. 716–719, 1996. View at Google Scholar · View at Scopus
  288. V. Mericq, F. Cassorla, T. Salazar et al., “Effects of eight months treatment with graded doses of a growth hormone (GH)-releasing peptide in GH-deficient children,” The Journal of Clinical Endocrinology & Metabolism, vol. 83, no. 7, pp. 2355–2360, 1998. View at Publisher · View at Google Scholar · View at Scopus
  289. C. Pihoker, T. M. Badger, G. A. Reynolds, and C. Y. Bowers, “Treatment effects of intranasal growth hormone releasing peptide-2 in children with short stature,” Journal of Endocrinology, vol. 155, no. 1, pp. 79–86, 1997. View at Publisher · View at Google Scholar · View at Scopus
  290. Z. Laron, J. Frenkel, R. Deghenghi, S. Anin, B. Klinger, and A. Silbergeld, “Intranasal administration of the GHRP hexarelin accelerates growth in short children,” Clinical Endocrinology, vol. 43, no. 5, pp. 631–635, 1995. View at Google Scholar · View at Scopus
  291. R. Nass, S. S. Pezzoli, M. C. Oliveri et al., “Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial,” Annals of Internal Medicine, vol. 149, no. 9, pp. 601–611, 2008. View at Google Scholar · View at Scopus
  292. H. Ariyasu, H. Iwakura, G. Yamada, K. Nakao, K. Kangawa, and T. Akamizu, “Efficacy of ghrelin as a therapeutic approach for age-related physiological changes,” Endocrinology, vol. 149, no. 7, pp. 3722–3728, 2008. View at Publisher · View at Google Scholar · View at Scopus
  293. A. Asakawa, A. Inui, M. Fujimiya et al., “Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin,” Gut, vol. 54, no. 1, pp. 18–24, 2005. View at Publisher · View at Google Scholar · View at Scopus
  294. D. Kohno, H. Sone, Y. Minokoshi, and T. Yada, “Ghrelin raises [Ca2+]i via AMPK in hypothalamic arcuate nucleus NPY neurons,” Biochemical and Biophysical Research Communications, vol. 366, no. 2, pp. 388–392, 2008. View at Publisher · View at Google Scholar · View at Scopus
  295. A. M. Naleid, M. K. Grace, D. E. Cummings, and A. S. Levine, “Ghrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens,” Peptides, vol. 26, no. 11, pp. 2274–2279, 2005. View at Publisher · View at Google Scholar · View at Scopus
  296. N. Nagaya, K. Miyatake, M. Uematsu et al., “Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure,” The Journal of Clinical Endocrinology & Metabolism, vol. 86, no. 12, pp. 5854–5859, 2001. View at Publisher · View at Google Scholar · View at Scopus
  297. N. Nagaya, M. Kojima, and K. Kangawa, “Ghrelin, a novel growth hormone-releasing peptide, in the treatment of cardiopulmonary-associated cachexia,” Internal Medicine, vol. 45, no. 3, pp. 127–134, 2006. View at Publisher · View at Google Scholar · View at Scopus
  298. N. M. Neary, C. J. Small, A. M. Wren et al., “Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial,” The Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 6, pp. 2832–2836, 2004. View at Publisher · View at Google Scholar · View at Scopus
  299. N. Nagaya and K. Kangawa, “Ghrelin improves left ventricular dysfunction and cardiac cachexia in heart failure,” Current Opinion in Pharmacology, vol. 3, no. 2, pp. 146–151, 2003. View at Publisher · View at Google Scholar · View at Scopus
  300. N. Nagaya, T. Itoh, S. Murakami et al., “Treatment of cachexia with ghrelin in patients with COPD,” Chest, vol. 128, no. 3, pp. 1187–1193, 2005. View at Publisher · View at Google Scholar · View at Scopus
  301. N. Nagaya, M. Uematsu, M. Kojima et al., “Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure,” Circulation, vol. 104, no. 12, pp. 1430–1435, 2001. View at Google Scholar · View at Scopus
  302. E. T. Vestergaard, T. K. Hansen, L. C. Gormsen et al., “Constant intravenous ghrelin infusion in healthy young men: clinical pharmacokinetics and metabolic effects,” American Journal of Physiology, vol. 292, no. 6, pp. E1829–E1836, 2007. View at Publisher · View at Google Scholar · View at Scopus
  303. M. Tschop, M. A. Statnick, T. M. Suter, and M. L. Heiman, “GH-releasing peptide-2 increases fat mass in mice lacking NPY: indication for a crucial mediating role of hypothalamic agouti-related protein,” Endocrinology, vol. 143, no. 2, pp. 558–568, 2002. View at Publisher · View at Google Scholar · View at Scopus
  304. F. Broglio, E. Arvat, A. Benso et al., “Ghrelin, a natural gh secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans,” The Journal of Clinical Endocrinology & Metabolism, vol. 86, no. 10, pp. 5083–5086, 2001. View at Publisher · View at Google Scholar · View at Scopus
  305. W. Zhang, B. Chai, J.-Y. Li, H. Wang, and M. W. Mulholland, “Effect of des-acyl ghrelin on adiposity and glucose metabolism,” Endocrinology, vol. 149, no. 9, pp. 4710–4716, 2008. View at Publisher · View at Google Scholar · View at Scopus
  306. E. T. Vestergaard, L. C. Gormsen, N. Jessen et al., “Ghrelin infusion in humans induces acute insulin resistance and lipolysis independent of growth hormone signaling,” Diabetes, vol. 57, no. 12, pp. 3205–3210, 2008. View at Publisher · View at Google Scholar · View at Scopus
  307. F. Broglio, F. Prodam, F. Riganti et al., “The continuous infusion of acylated ghrelin enhances growth hormone secretion and worsens glucose metabolism in humans,” Journal of Endocrinological Investigation, vol. 31, no. 9, pp. 788–794, 2008. View at Google Scholar · View at Scopus
  308. M. S. Duxbury, T. Waseem, H. Ito et al., “Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness,” Biochemical and Biophysical Research Communications, vol. 309, no. 2, pp. 464–468, 2003. View at Publisher · View at Google Scholar · View at Scopus
  309. P. J. D. Delhanty, P. M. Van Koetsveld, C. Gauna et al., “Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway,” American Journal of Physiology, vol. 293, no. 1, pp. E302–E309, 2007. View at Publisher · View at Google Scholar · View at Scopus
  310. A. Kheradmand, L. Roshangar, and M. Taati, “The role of ghrelin on the morphometry and intracellular changes in the rat testis,” Tissue and Cell, vol. 41, no. 2, pp. 105–111, 2009. View at Publisher · View at Google Scholar · View at Scopus
  311. T. Sugino, J. Yamaura, M. Yamagishi et al., “Involvement of cholinergic neurons in the regulation of the ghrelin secretory response to feeding in sheep,” Biochemical and Biophysical Research Communications, vol. 304, no. 2, pp. 308–312, 2003. View at Publisher · View at Google Scholar · View at Scopus
  312. A. M. Wren, C. J. Small, C. R. Abbott et al., “Ghrelin causes hyperphagia and obesity in rats,” Diabetes, vol. 50, no. 7–12, pp. 2540–2547, 2001. View at Google Scholar · View at Scopus
  313. A. M. Wren, C. J. Small, H. L. Ward et al., “The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion,” Endocrinology, vol. 141, no. 11, pp. 4325–4328, 2000. View at Google Scholar · View at Scopus
  314. C. B. Lawrence, A. C. Snape, F. M.-H. Baudoin, and S. M. Luckman, “Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers,” Endocrinology, vol. 143, no. 1, pp. 155–162, 2002. View at Publisher · View at Google Scholar · View at Scopus
  315. H. Kaiya, M. Furuse, M. Miyazato, and K. Kangawa, “Current knowledge of the roles of ghrelin in regulating food intake and energy balance in birds,” General and Comparative Endocrinology, vol. 163, no. 1-2, pp. 33–38, 2009. View at Publisher · View at Google Scholar · View at Scopus
  316. I. D. Blum, Z. Patterson, R. Khazall et al., “Reduced anticipatory locomotor responses to scheduled meals in ghrelin receptor deficient mice,” Neuroscience, vol. 164, no. 2, pp. 351–359, 2009. View at Publisher · View at Google Scholar · View at Scopus
  317. X. Chen, Y.-L. Ge, Z.-Y. Jiang, C.-Q. Liu, I. Depoortere, and T. L. Peeters, “Effects of ghrelin on hypothalamic glucose responding neurons in rats,” Brain Research, vol. 1055, no. 1-2, pp. 131–136, 2005. View at Publisher · View at Google Scholar · View at Scopus
  318. S. L. Dickson and S. M. Luckman, “Induction of c-fos messenger ribonucleic acid in neuropeptide Y and growth hormone (GH)-releasing factor neurons in the rat arcuate nucleus following systemic injection of the GH secretagogue, GH-releasing peptide-6,” Endocrinology, vol. 138, no. 2, pp. 771–777, 1997. View at Publisher · View at Google Scholar · View at Scopus
  319. J. Kamegai, H. Tamura, T. Shimizu, S. Ishii, H. Sugihara, and I. Wakabayashi, “Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats,” Diabetes, vol. 50, no. 7–12, pp. 2438–2443, 2001. View at Google Scholar · View at Scopus
  320. D. Kohno, H.-Z. Gao, S. Muroya, S. Kikuyama, and T. Yada, “Ghrelin directly interacts with neuropeptide-Y-containing neurons in the rat arcuate nucleus: Ca2+ signaling via protein kinase A and N-type channel-dependent mechanisms and cross-talk with leptin and orexin,” Diabetes, vol. 52, no. 4, pp. 948–956, 2003. View at Publisher · View at Google Scholar · View at Scopus
  321. H. Y. Chen, M. E. Trumbauer, A. S. Chen et al., “Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein,” Endocrinology, vol. 145, no. 6, pp. 2607–2612, 2004. View at Publisher · View at Google Scholar · View at Scopus
  322. E. Keen-Rhinehart and T. J. Bartness, “NPY Y1 receptor is involved in ghrelin- and fasting-induced increases in foraging, food hoarding, and food intake,” American Journal of Physiology, vol. 292, no. 4, pp. R1728–R1737, 2007. View at Publisher · View at Google Scholar · View at Scopus
  323. R. Nogueiras, S. Tovar, S. E. Mitchell et al., “Regulation of growth hormone secretagogue receptor gene expression in the arcuate nuclei of the rat by leptin and ghrelin,” Diabetes, vol. 53, no. 10, pp. 2552–2558, 2004. View at Publisher · View at Google Scholar · View at Scopus
  324. M. A. Cowley, R. D. Cone, P. Enriori, I. Louiselle, S. M. Williams, and A. E. Evans, “Electrophysiological actions of peripheral hormones on melanocortin neurons,” Annals of the New York Academy of Sciences, vol. 994, pp. 175–186, 2003. View at Google Scholar · View at Scopus
  325. G. A. Bray, “Afferent signals regulating food intake,” Proceedings of the Nutrition Society, vol. 59, no. 3, pp. 373–384, 2000. View at Google Scholar · View at Scopus
  326. E. Valassi, M. Scacchi, and F. Cavagnini, “Neuroendocrine control of food intake,” Nutrition, Metabolism and Cardiovascular Diseases, vol. 18, no. 2, pp. 158–168, 2008. View at Publisher · View at Google Scholar · View at Scopus
  327. E. C. Villanueva, H. Munzberg, D. Cota et al., “Complex regulation of mammalian target of rapamycin complex 1 in the basomedial hypothalamus by leptin and nutritional status,” Endocrinology, vol. 150, no. 10, pp. 4541–4551, 2009. View at Publisher · View at Google Scholar · View at Scopus
  328. K. Ohno and T. Sakurai, “Orexin neuronal circuitry: role in the regulation of sleep and wakefulness,” Frontiers in Neuroendocrinology, vol. 29, no. 1, pp. 70–87, 2008. View at Publisher · View at Google Scholar · View at Scopus
  329. K. Toshinai, Y. Date, N. Murakami et al., “Ghrelin-induced food intake is mediated via the orexin pathway,” Endocrinology, vol. 144, no. 4, pp. 1506–1512, 2003. View at Publisher · View at Google Scholar · View at Scopus
  330. B. Kola, E. Hubina, S. A. Tucci et al., “Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase,” Journal of Biological Chemistry, vol. 280, no. 26, pp. 25196–25201, 2005. View at Publisher · View at Google Scholar · View at Scopus
  331. M. Osto, P. Y. Wielinga, B. Alder, N. Walser, and T. A. Lutz, “Modulation of the satiating effect of amylin by central ghrelin, leptin and insulin,” Physiology and Behavior, vol. 91, no. 5, pp. 566–572, 2007. View at Publisher · View at Google Scholar · View at Scopus
  332. M. Arnold, A. Mura, W. Langhans, and N. Geary, “Gut vagal afferents are not necessary for the eating-stimulatory effect of intraperitoneally injected ghrelin in the rat,” Journal of Neuroscience, vol. 26, no. 43, pp. 11052–11060, 2006. View at Publisher · View at Google Scholar · View at Scopus
  333. Y. Date, M. Nakazato, N. Murakami, M. Kojima, K. Kangawa, and S. Matsukura, “Ghrelin acts in the central nervous system to stimulate gastric acid secretion,” Biochemical and Biophysical Research Communications, vol. 280, no. 3, pp. 904–907, 2001. View at Publisher · View at Google Scholar · View at Scopus
  334. Y. Date, N. Murakami, K. Toshinai et al., “The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats,” Gastroenterology, vol. 123, no. 4, pp. 1120–1128, 2002. View at Publisher · View at Google Scholar · View at Scopus
  335. Y. Kawahara, H. Kawahara, F. Kaneko et al., “Peripherally administered ghrelin induces bimodal effects on the mesolimbic dopamine system depending on food-consumptive states,” Neuroscience, vol. 161, no. 3, pp. 855–864, 2009. View at Publisher · View at Google Scholar · View at Scopus
  336. C. W. Le Roux, N. M. Neary, T. J. Halsey et al., “Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy,” The Journal of Clinical Endocrinology & Metabolism, vol. 90, no. 8, pp. 4521–4524, 2005. View at Publisher · View at Google Scholar · View at Scopus
  337. R. Malcher-Lopes, S. Di, V. S. Marcheselli et al., “Opposing crosstalk between leptin and glucocorticoids rapidly modulates synaptic excitation via endocannabinoid release,” Journal of Neuroscience, vol. 26, no. 24, pp. 6643–6650, 2006. View at Publisher · View at Google Scholar · View at Scopus
  338. S. A. Tucci, E. K. Rogers, M. Korbonits, and T. C. Kirkham, “The cannabinoid CB1 receptor antagonist SR141716 blocks the orexigenic effects of intrahypothalamic ghrelin,” British Journal of Pharmacology, vol. 143, no. 5, pp. 520–523, 2004. View at Publisher · View at Google Scholar · View at Scopus
  339. L. Degen, J. Drewe, F. Piccoli et al., “Effect of CCK-1 receptor blockade on ghrelin and PYY secretion in men,” American Journal of Physiology, vol. 292, no. 4, pp. R1391–R1399, 2007. View at Publisher · View at Google Scholar · View at Scopus
  340. F. Lippl, F. Kircher, J. Erdmann, H.-D. Allescher, and V. Schusdziarra, “Effect of GIP, GLP-1, insulin and gastrin on ghrelin release in the isolated rat stomach,” Regulatory Peptides, vol. 119, no. 1-2, pp. 93–98, 2004. View at Publisher · View at Google Scholar · View at Scopus
  341. V. D. Dixit, H. Yang, A. Cooper-Jenkins, B. B. Giri, K. Patel, and D. D. Taub, “Reduction of T cell-derived ghrelin enhances proinflammatory cytokine expression: implications for age-associated increases in inflammation,” Blood, vol. 113, no. 21, pp. 5202–5205, 2009. View at Publisher · View at Google Scholar · View at Scopus
  342. S. Koda, Y. Date, N. Murakami et al., “The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in rats,” Endocrinology, vol. 146, no. 5, pp. 2369–2375, 2005. View at Publisher · View at Google Scholar · View at Scopus
  343. Y. Date, K. Toshinai, S. Koda et al., “Peripheral interaction of ghrelin with cholecystokinin on feeding regulation,” Endocrinology, vol. 146, no. 8, pp. 3518–3525, 2005. View at Publisher · View at Google Scholar · View at Scopus
  344. R. Wu, M. Zhou, W. Dong et al., “Ghrelin hyporesponsiveness contributes to age-related hyperinflammation in septic shock,” Annals of Surgery, vol. 250, no. 1, pp. 126–133, 2009. View at Publisher · View at Google Scholar · View at Scopus
  345. X.-B. Gao, “Electrophysiological effects of MCH on neurons in the hypothalamus,” Peptides, vol. 30, no. 11, pp. 2025–2030, 2009. View at Publisher · View at Google Scholar · View at Scopus
  346. Z. Xin, M. D. Serby, H. Zhao et al., “Discovery and pharmacological evaluation of growth hormone secretagogue receptor antagonists,” Journal of Medicinal Chemistry, vol. 49, no. 15, pp. 4459–4469, 2006. View at Publisher · View at Google Scholar · View at Scopus
  347. N. Salome, D. Haage, D. Perrissoud et al., “Anorexigenic and electrophysiological actions of novel ghrelin receptor (GHS-R1A) antagonists in rats,” European Journal of Pharmacology, vol. 612, no. 1–3, pp. 167–173, 2009. View at Publisher · View at Google Scholar · View at Scopus
  348. L. Wang, V. Martinez, J. E. Rivier, and Y. Taché, “Peripheral urocortin inhibits gastric emptying and food intake in mice: differential role of CRF receptor 2,” American Journal of Physiology, vol. 281, no. 5, pp. R1401–R1410, 2001. View at Google Scholar · View at Scopus
  349. S. R. Cunha and K. E. Mayo, “Ghrelin and growth hormone (GH) secretagogues potentiate GH-releasing hormone (GHRH)-induced cyclic adenosine 3,5-monophosphate production in cells expressing transfected GHRH and GH secretagogue receptors,” Endocrinology, vol. 143, no. 12, pp. 4570–4582, 2002. View at Publisher · View at Google Scholar · View at Scopus
  350. R. Xu, Y. Zhao, and C. Chen, “Growth hormone-releasing peptide-2 reduces inward rectifying K+ currents via a PKA-cAMP-mediated signalling pathway in ovine somatoropes,” Journal of Physiology, vol. 545, no. 2, pp. 421–433, 2002. View at Publisher · View at Google Scholar · View at Scopus
  351. C. Chen and I. J. Clarke, “Effects of growth hormone-releasing peptide-2 (GHRP-2) on membrane Ca2+ permeability in cultured ovine somatotrophs,” Journal of Neuroendocrinology, vol. 7, no. 3, pp. 179–186, 1995. View at Google Scholar · View at Scopus
  352. M. Kuramochi, D. Kohno, T. Onaka, S. Kato, and T. Yada, “Galanin-like peptide and ghrelin increase cytosolic Ca2+ in neurons containing growth hormone-releasing hormone in the arcuate nucleus,” Regulatory Peptides, vol. 126, no. 1-2, pp. 85–89, 2005. View at Publisher · View at Google Scholar · View at Scopus
  353. S. Shioda, F. Takenoya, M. Yagi, L. Wang, Y. Hori, and H. Kageyama, “Neural networks of several novel neuropeptides involved in feeding regulation,” Nutrition, vol. 24, no. 9, pp. 848–853, 2008. View at Publisher · View at Google Scholar · View at Scopus
  354. A. Johansson, R. Fredriksson, S. Winnergren, A.-L. Hulting, H. B. Schioth, and J. Lindblom, “The relative impact of chronic food restriction and acute food deprivation on plasma hormone levels and hypothalamic neuropeptide expression,” Peptides, vol. 29, no. 9, pp. 1588–1595, 2008. View at Publisher · View at Google Scholar · View at Scopus
  355. A. P. Coll, I. S. Farooqi, and S. O'Rahilly, “The hormonal control of food intake,” Cell, vol. 129, no. 2, pp. 251–262, 2007. View at Publisher · View at Google Scholar · View at Scopus
  356. Z. Hu, H. C. Seung, G. van Haasteren, J. Wang, and M. D. Lane, “Effect of centrally administered C75, a fatty acid synthase inhibitor, on ghrelin secretion and its downstream effects,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 11, pp. 3972–3977, 2005. View at Publisher · View at Google Scholar · View at Scopus
  357. Y. C. L. Tung, A. K. Hewson, R. N. Carter, and S. L. Dickson, “Central responsiveness to a grelin mimetic (GHRP-6) is rapidly altered by acute changes in nutritional status in rats,” Journal of Neuroendocrinology, vol. 17, no. 6, pp. 387–393, 2005. View at Publisher · View at Google Scholar · View at Scopus
  358. A. Tups, M. Helwig, R. M. H. Khorooshi, Z. A. Archer, M. Klingensport, and J. G. Mercer, “Circulating ghrelin levels and central ghrelin receptor expression are elevated in response to food deprivation in a seasonal mammal (Phodopus sungorus),” Journal of Neuroendocrinology, vol. 16, no. 11, pp. 922–928, 2004. View at Publisher · View at Google Scholar · View at Scopus
  359. C.-X. Yi, J. van der Vliet, J. Dai, G. Yin, L. Ru, and R. M. Buijs, “Ventromedial arcuate nucleus communicates peripheral metabolic information to the suprachiasmatic nucleus,” Endocrinology, vol. 147, no. 1, pp. 283–294, 2006. View at Publisher · View at Google Scholar · View at Scopus
  360. H. Tamura, J. Kamegai, T. Shimizu, S. Ishii, H. Sugihara, and S. Oikawa, “Ghrelin stimulates GH but not food intake in arcuate nucleus ablated rats,” Endocrinology, vol. 143, no. 9, pp. 3268–3275, 2002. View at Publisher · View at Google Scholar · View at Scopus
  361. L. M. Seoane, M. Lopez, S. Tovar, F. F. Casanueva, R. Senaris, and C. Dieguez, “Agouti-related peptide, neuropeptide Y, and somatostatin-producing neurons are targets for ghrelin actions in the rat hypothalamus,” Endocrinology, vol. 144, no. 2, pp. 544–551, 2003. View at Publisher · View at Google Scholar · View at Scopus
  362. T. Riediger, C. Bothe, C. Becskei, and T. A. Lutz, “Peptide YY directly inhibits ghrelin-activated neurons of the arcuate nucleus and reverses fasting-induced c-Fos expression,” Neuroendocrinology, vol. 79, no. 6, pp. 317–326, 2004. View at Publisher · View at Google Scholar · View at Scopus
  363. M. Patterson, K. G. Murphy, S. R. Patel et al., “Hypothalamic injection of oxyntomodulin suppresses circulating ghrelin-like immunoreactivity,” Endocrinology, vol. 150, no. 8, pp. 3513–3520, 2009. View at Publisher · View at Google Scholar · View at Scopus
  364. V. Monti, J. J. Carlson, S. C. Hunt, and T. D. Adams, “Relationship of ghrelin and leptin hormones with body mass index and waist circumference in a random sample of adults,” Journal of the American Dietetic Association, vol. 106, no. 6, pp. 822–828, 2006. View at Publisher · View at Google Scholar · View at Scopus
  365. T. Ida, K. Mori, M. Miyazato et al., “Neuromedin S is a novel anorexigenic hormone,” Endocrinology, vol. 146, no. 10, pp. 4217–4223, 2005. View at Publisher · View at Google Scholar · View at Scopus
  366. Y. Kurose, J. Iqbal, A. Rao et al., “Changes in expression of the genes for the leptin receptor and the growth hormone-releasing peptide/ghrelin receptor in the hypothalamic arcuate nucleus with long-term manipulation of adiposity by dietary means,” Journal of Neuroendocrinology, vol. 17, no. 6, pp. 331–340, 2005. View at Publisher · View at Google Scholar · View at Scopus
  367. P. Kobelt, J. J. Tebbe, I. Tjandra et al., “CCK inhibits the orexigenic effect of peripheral ghrelin,” American Journal of Physiology, vol. 288, no. 3, pp. R751–R758, 2005. View at Publisher · View at Google Scholar · View at Scopus
  368. P. Kobelt, M. Goebel, A. Stengel et al., “Bombesin, but not amylin, blocks the orexigenic effect of peripheral ghrelin,” American Journal of Physiology, vol. 291, no. 4, pp. R903–R913, 2006. View at Publisher · View at Google Scholar · View at Scopus
  369. J. Buyse, S. Janssen, S. Geelissen et al., “Ghrelin modulates fatty acid synthase and related transcription factor mRNA levels in a tissue-specific manner in neonatal broiler chicks,” Peptides, vol. 30, no. 7, pp. 1342–1347, 2009. View at Publisher · View at Google Scholar · View at Scopus
  370. G. De Lartigue, R. Dimaline, A. Varro, and G. J. Dockray, “Cocaine- and amphetamine-regulated transcript: stimulation of expression in rat vagal afferent neurons by cholecystokinin and suppression by ghrelin,” Journal of Neuroscience, vol. 27, no. 11, pp. 2876–2882, 2007. View at Publisher · View at Google Scholar · View at Scopus
  371. H. Shimizu, S. Oh-I, K. Hashimoto et al., “Peripheral administration of nesfatin-1 reduces food intake in mice: the leptin-independent mechanism,” Endocrinology, vol. 150, no. 2, pp. 662–671, 2009. View at Publisher · View at Google Scholar · View at Scopus
  372. K. Toshinai, M. S. Mondal, T. Shimbara et al., “Ghrelin stimulates growth hormone secretion and food intake in aged rats,” Mechanisms of Ageing and Development, vol. 128, no. 2, pp. 182–186, 2007. View at Publisher · View at Google Scholar · View at Scopus
  373. S. Luquet, F. A. Perez, T. S. Hnasko, and R. D. Palmiter, “NPY/AgRP neurons are essentials for feeding in adult mice but can be ablated in neonates,” Science, vol. 310, no. 5748, pp. 683–685, 2005. View at Publisher · View at Google Scholar · View at Scopus
  374. A. Solomon, B. A. De Fanti, and J. A. Martínez, “Peripheral ghrelin interacts with orexin neurons in glucostatic signalling,” Regulatory Peptides, vol. 144, no. 1–3, pp. 17–24, 2007. View at Publisher · View at Google Scholar · View at Scopus
  375. S. Akimoto-Takano, C. Sakurai, S. Kanai, H. Hosoya, M. Ohta, and K. Miyasaka, “Differences in the appetite-stimulating effect of orexin, neuropeptide Y and ghrelin among young, adult and old rats,” Neuroendocrinology, vol. 82, no. 5-6, pp. 256–263, 2006. View at Publisher · View at Google Scholar · View at Scopus
  376. Y. B. Shrestha, K. Wickwire, and S. Giraudo, “Effect of reducing hypothalamic ghrelin receptor gene expression on energy balance,” Peptides, vol. 30, no. 7, pp. 1336–1341, 2009. View at Publisher · View at Google Scholar · View at Scopus
  377. Y. Shimomura, M. Harada, M. Goto et al., “Identification of neuropeptide W as the endogenous ligand for orphan G-protein-coupled receptors GPR7 and GPR8,” Journal of Biological Chemistry, vol. 277, no. 39, pp. 35826–35832, 2002. View at Publisher · View at Google Scholar · View at Scopus
  378. F. Takenoya, S. Kitamura, H. Kageyama et al., “Neuronal interactions between neuropeptide W- and orexin- or melanin-concentrating hormone-containing neurons in the rat hypothalamus,” Regulatory Peptides, vol. 145, no. 1–3, pp. 159–164, 2008. View at Publisher · View at Google Scholar · View at Scopus
  379. C. Acuna-Goycolea and A. N. van den Pol, “Neuroendocrine proopiomelanocortin neurons are excited by hypocretin/orexin,” Journal of Neuroscience, vol. 29, no. 5, pp. 1503–1513, 2009. View at Publisher · View at Google Scholar · View at Scopus
  380. A. G. Roseberry, H. Liu, A. C. Jackson, X. Cai, and J. M. Friedman, “Neuropeptide Y-mediated inhibition of proopiomelanocortin neurons in the arcuate nucleus shows enhanced desensitization in ob/ob mice,” Neuron, vol. 41, no. 5, pp. 711–722, 2004. View at Publisher · View at Google Scholar · View at Scopus
  381. C. Broberger, M. Landry, H. Wong, J. N. Walsh, and T. Hokfelt, “Subtypes Y1 and Y2 of the neuropeptide Y receptor are respectively expressed in pro-opiomelanocortin- and neuropeptide-Y-containing neurons of the rat hypothalamic arcuate nucleus,” Neuroendocrinology, vol. 66, no. 6, pp. 393–408, 1997. View at Google Scholar · View at Scopus
  382. J.-H. Wang, F. Wang, M.-J. Yang et al., “Leptin regulated calcium channels of neuropeptide Y and proopiomelanocortin neurons by activation of different signal pathways,” Neuroscience, vol. 156, no. 1, pp. 89–98, 2008. View at Publisher · View at Google Scholar · View at Scopus
  383. J.-L. Guan, Q.-P. Wang, H. Kageyama et al., “Synaptic interactions between ghrelin- and neuropeptide Y-containing neurons in the rat arcuate nucleus,” Peptides, vol. 24, no. 12, pp. 1921–1928, 2003. View at Publisher · View at Google Scholar · View at Scopus
  384. J.-L. Guan, T. Saotome, Q.-P. Wang et al., “Orexinegic innervation of POMC-containing neurons in the rat arcuate nucleus,” NeuroReport, vol. 12, no. 3, pp. 547–551, 2001. View at Google Scholar · View at Scopus
  385. H. Funahashi, F. Takenoya, J.-L. Guan, H. Kageyama, T. Yada, and S. Shioda, “Hypothalamic neuronal networks and feeding-related peptides involved in the regulation of feeding,” Anatomical Science International, vol. 78, no. 3, pp. 123–138, 2003. View at Google Scholar · View at Scopus
  386. A. Jureus, M. J. Cunningham, M. E. McClain, D. K. Clifton, and R. A. Steiner, “Galanin-like peptide (GALP) is a target for regulation by leptin in the hypothalamus of the rat,” Endocrinology, vol. 141, no. 7, pp. 2703–2706, 2000. View at Publisher · View at Google Scholar · View at Scopus
  387. D. G. Baskin, T. M. Hahn, and M. W. Schwartz, “Leptin sensitive neurons in the hypothalamus,” Hormone and Metabolic Research, vol. 31, no. 5, pp. 345–350, 1999. View at Google Scholar · View at Scopus
  388. H. Ariyasu, K. Takaya, T. Tagami et al., “Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans,” The Journal of Clinical Endocrinology & Metabolism, vol. 86, no. 10, pp. 4753–4758, 2001. View at Publisher · View at Google Scholar · View at Scopus
  389. D. E. Cummings, R. S. Frayo, C. Marmonier, R. Aubert, and D. Chapelot, “Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues,” American Journal of Physiology, vol. 287, no. 2, pp. E297–E304, 2004. View at Publisher · View at Google Scholar · View at Scopus
  390. A. N. van den Pol, Y. Yao, L.-Y. Fu et al., “Neuromedin B and gastrin-releasing peptide excite arcuate nucleus neuropeptide Y neurons in a novel transgenic mouse expressing strong renilla green fluorescent protein in NPY neurons,” Journal of Neuroscience, vol. 29, no. 14, pp. 4622–4639, 2009. View at Publisher · View at Google Scholar · View at Scopus
  391. T. Akamizu, K. Takaya, T. Irako et al., “Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects,” European Journal of Endocrinology, vol. 150, no. 4, pp. 447–455, 2004. View at Publisher · View at Google Scholar · View at Scopus
  392. J. S. Davies, P. Kotokorpi, S. R. Eccles et al., “Ghrelin induces abdominal obesity via GHS-R-dependent lipid retention,” Molecular Endocrinology, vol. 23, no. 6, pp. 914–924, 2009. View at Publisher · View at Google Scholar · View at Scopus
  393. E. A. Garcia, P. King, K. Sidhu et al., “The role of ghrelin and ghrelin-receptor gene variants and promoter activity in type 2 diabetes,” European Journal of Endocrinology, vol. 161, no. 2, pp. 307–315, 2009. View at Publisher · View at Google Scholar · View at Scopus
  394. F. Tremblay, M. Perreault, L. D. Klaman, J. F. Tobin, E. Smith, and R. E. Gimeno, “Normal food intake and body weight in mice lacking the G protein-coupled receptor GPR39,” Endocrinology, vol. 148, no. 2, pp. 501–506, 2007. View at Publisher · View at Google Scholar · View at Scopus
  395. B. De Smet, T. Thijs, T. L. Peeters, and I. Depoortere, “Effect of peripheral obestatin on gastric emptying and intestinal contractility in rodents,” Neurogastroenterology and Motility, vol. 19, no. 3, pp. 211–217, 2007. View at Publisher · View at Google Scholar · View at Scopus
  396. D. Moechars, I. Depoortere, B. Moreaux et al., “Altered gastrointestinal and metabolic function in the GPR39-obestatin receptor-knockout mouse,” Gastroenterology, vol. 131, no. 4, pp. 1131–1141, 2006. View at Publisher · View at Google Scholar · View at Scopus
  397. G. Gourcerol, T. Coskun, L. S. Craft et al., “Preproghrelin-derived peptide, obestatin, fails to influence food intake in lean or obese rodents,” Obesity, vol. 15, no. 11, pp. 2643–2652, 2007. View at Publisher · View at Google Scholar · View at Scopus
  398. G. Gourcerol, M. Million, D. W. Adelson et al., “Lack of interaction between peripheral injection of CCK and obestatin in the regulation of gastric satiety signaling in rodents,” Peptides, vol. 27, no. 11, pp. 2811–2819, 2006. View at Publisher · View at Google Scholar · View at Scopus
  399. P. Kobelt, A.-S. Wisser, A. Stengel et al., “Peripheral obestatin has no effect on feeding behavior and brain Fos expression in rodents,” Peptides, vol. 29, no. 6, pp. 1018–1027, 2008. View at Publisher · View at Google Scholar · View at Scopus
  400. M. G.-S. Frutos, L. Cacicedo, C. Fernández et al., “Insights into a role of GH secretagogues in reversing the age-related decline in the GH/IGF-I axis,” American Journal of Physiology, vol. 293, no. 5, pp. E1140–E1152, 2007. View at Publisher · View at Google Scholar · View at Scopus
  401. R. Nogueiras, P. Pfluger, S. Tovar et al., “Effects of obestatin on energy balance and growth hormone secretion in rodents,” Endocrinology, vol. 148, no. 1, pp. 21–26, 2007. View at Publisher · View at Google Scholar · View at Scopus
  402. D. Yamamoto, N. Ikeshita, R. Daito et al., “Neither intravenous nor intracerebroventricular administration of obestatin affects the secretion of GH, PRL, TSH and ACTH in rats,” Regulatory Peptides, vol. 138, no. 2-3, pp. 141–144, 2007. View at Publisher · View at Google Scholar · View at Scopus
  403. W. K. Samson, M. M. White, C. Price, and A. V. Ferguson, “Obestatin acts in brain to inhibit thirst,” American Journal of Physiology, vol. 292, no. 1, pp. R637–R643, 2007. View at Publisher · View at Google Scholar · View at Scopus
  404. K. Ataka, A. Inui, A. Asakawa, I. Kato, and M. Fujimiya, “Obestatin inhibits motor activity in the antrum and duodenum in the fed state of conscious rats,” American Journal of Physiology, vol. 294, no. 5, pp. G1210–G1218, 2008. View at Publisher · View at Google Scholar · View at Scopus
  405. M. Volante, R. Rosas, P. Ceppi et al., “Obestatin in human neuroendocrine tissues and tumours: expression and effect on tumour growth,” Journal of Pathology, vol. 218, no. 4, pp. 458–466, 2009. View at Publisher · View at Google Scholar · View at Scopus
  406. A. V. Tsolakis, L. Grimelius, M. Stridsberg et al., “Obestatin/ghrelin cells in normal mucosa and endocrine tumours of the stomach,” European Journal of Endocrinology, vol. 160, no. 6, pp. 941–949, 2009. View at Publisher · View at Google Scholar · View at Scopus
  407. C.-M. Zhao, M. W. Furnes, B. Stenstrom, B. Kulseng, and D. Chen, “Characterization of obestatin- and ghrelin-producing cells in the gastrointestinal tract and pancreas of rats: an immunohistochemical and electron-microscopic study,” Cell and Tissue Research, vol. 331, no. 3, pp. 575–587, 2008. View at Publisher · View at Google Scholar · View at Scopus
  408. M. Kerem, B. Salman, S. Ozsoy et al., “Exogenous ghrelin enhances endocrine and exocrine regeneration in pancreatectomized rats,” Journal of Gastrointestinal Surgery, vol. 13, no. 4, pp. 775–783, 2009. View at Publisher · View at Google Scholar · View at Scopus
  409. R. Granata, F. Settanni, D. Gallo et al., “Obestatin promotes survival of pancreatic ß-cells and human islets and induces expression of genes involved in the regulation of ß-cell mass and function,” Diabetes, vol. 57, no. 4, pp. 967–979, 2008. View at Publisher · View at Google Scholar · View at Scopus
  410. J. V. Zhang, H. Jahr, C.-W. Luo et al., “Obestatin induction of early-response gene expression in gastrointestinal and adipose tissues and the mediatory role of G protein-coupled receptor, GPR39,” Molecular Endocrinology, vol. 22, no. 6, pp. 1464–1475, 2008. View at Publisher · View at Google Scholar · View at Scopus
  411. É. Szentirmai, L. Kapás, Y. Sun, R. G. Smith, and J. M. Krueger, “The preproghrelin gene is required for the normal integration of thermoregulation and sleep in mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 33, pp. 14069–14074, 2009. View at Publisher · View at Google Scholar · View at Scopus
  412. W. Wei, X. Qi, J. Reed et al., “Effect of chronic hyperghrelinemia on ingestive action of ghrelin,” American Journal of Physiology, vol. 290, no. 3, pp. R803–R808, 2006. View at Publisher · View at Google Scholar · View at Scopus
  413. E. Bresciani, N. Pitsikas, L. Tamiazzo et al., “Feeding behavior during long-term hexarelin administration in young and old rats,” Journal of Endocrinological Investigation, vol. 31, no. 7, pp. 647–652, 2008. View at Google Scholar · View at Scopus
  414. N. Nagaya, J. Moriya, Y. Yasumura et al., “Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure,” Circulation, vol. 110, no. 24, pp. 3674–3679, 2004. View at Publisher · View at Google Scholar · View at Scopus
  415. D. R. Ashby, H. E. Ford, K. J. Wynne et al., “Sustained appetite improvement in malnourished dialysis patients by daily ghrelin treatment,” Kidney International, vol. 76, no. 2, pp. 199–206, 2009. View at Publisher · View at Google Scholar · View at Scopus
  416. T. Akamizu, H. Iwakura, H. Ariyasu et al., “Effects of ghrelin treatment on patients undergoing total hip replacement for osteoarthritis: different outcomes from studies in patients with cardiac and pulmonary cachexia,” Journal of the American Geriatrics Society, vol. 56, no. 12, pp. 2363–2365, 2008. View at Publisher · View at Google Scholar · View at Scopus
  417. S. Blüher and C. S. Mantzoros, “Leptin in humans: lessons from translational research,” American Journal of Clinical Nutrition, vol. 89, no. 3, pp. 991S–997S, 2009. View at Publisher · View at Google Scholar · View at Scopus
  418. V. Scott, D. M. McDade, and S. M. Luckman, “Rapid changes in the sensitivity of arcuate nucleus neurons to central ghrelin in relation to feeding status,” Physiology and Behavior, vol. 90, no. 1, pp. 180–185, 2007. View at Publisher · View at Google Scholar · View at Scopus
  419. P. K. Olszewski, D. Li, M. K. Grace, C. J. Billington, C. M. Kotz, and A. S. Levine, “Neural basis of orexigenic effects of ghrelin acting within lateral hypothalamus,” Peptides, vol. 24, no. 4, pp. 597–602, 2003. View at Publisher · View at Google Scholar · View at Scopus
  420. S. Strassburg, S. D. Anker, T. R. Castaneda et al., “Long-term effects of ghrelin and ghrelin receptor agonists on energy balance in rats,” American Journal of Physiology, vol. 295, no. 1, pp. E78–E84, 2008. View at Publisher · View at Google Scholar · View at Scopus
  421. G. B. Thomas, P. A. Bennett, D. F. Carmignac, and I. C. Robinson, “Glucocorticoid regulation of growth hormone (GH) secretagogue-induced growth responses and GH secretagogue receptor expression in the rat,” Growth Hormone and IGF Research, vol. 10, no. 1, pp. 45–52, 2000. View at Publisher · View at Google Scholar · View at Scopus
  422. P. A. Bennett, G. B. Thomas, A. D. Howard et al., “Hypothalamic growth hormone secretagogue-receptor (GHS-R) expression is regulated by growth hormone in the rat,” Endocrinology, vol. 138, no. 11, pp. 4552–4557, 1997. View at Publisher · View at Google Scholar · View at Scopus
  423. J. Kamegai, I. Wakabayashi, R. D. Kineman, and L. A. Frohman, “Growth hormone-releasing hormone receptor (GHRH-R) and growth hormone secretagogue receptor (GHS-R) mRNA levels during postnatal development in male and female rats,” Journal of Neuroendocrinology, vol. 11, no. 4, pp. 299–306, 1999. View at Publisher · View at Google Scholar · View at Scopus
  424. M. C. Machado, S. Valeria de Sa, M. L. Correa-Giannella et al., “Association between tumoral GH-releasing peptide receptor type 1a mRNA expression and in vivo response to GH-releasing peptide-6 in ACTH-dependent Cushing's syndrome patients,” European Journal of Endocrinology, vol. 158, no. 5, pp. 605–613, 2008. View at Publisher · View at Google Scholar · View at Scopus
  425. S. D. Katugampola, Z. Pallikaros, and A. P. Davenport, “[125I-his9]-ghrelin, a novel radioligand for localizing GHS orphan receptors in human and rat tissue; up-regulation of receptors with atherosclerosis,” British Journal of Pharmacology, vol. 134, no. 1, pp. 143–149, 2001. View at Google Scholar · View at Scopus
  426. D. E. Cummings, D. S. Weigle, R. S. Frayo et al., “Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery,” The New England Journal of Medicine, vol. 346, no. 21, pp. 1623–1630, 2002. View at Publisher · View at Google Scholar · View at Scopus
  427. C. L. Roth, T. Reinehr, G.-H. Schernthaner, H.-P. Kopp, S. Kriwanek, and G. Schernthaner, “Ghrelin and obestatin levels in severely obese women before and after weight loss after Roux-en-Y gastric bypass surgery,” Obesity Surgery, vol. 19, no. 1, pp. 29–35, 2009. View at Publisher · View at Google Scholar · View at Scopus
  428. M. Faraj, P. J. Havel, S. Phelis, D. Blank, A. D. Sniderman, and K. Cianflone, “Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects,” The Journal of Clinical Endocrinology & Metabolism, vol. 88, no. 4, pp. 1594–1602, 2003. View at Publisher · View at Google Scholar · View at Scopus
  429. J. Korner, W. Inabnet, G. Febres et al., “Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass,” International Journal of Obesity, vol. 33, no. 7, pp. 786–795, 2009. View at Publisher · View at Google Scholar · View at Scopus
  430. D. Foschi, F. Corsi, F. Colombo et al., “Different effects of vertical banded gastroplasty and Roux-en-Y gastric bypass on meal inhibition of ghrelin secretion in morbidly obese patients,” Journal of Investigative Surgery, vol. 21, no. 2, pp. 77–81, 2008. View at Publisher · View at Google Scholar · View at Scopus
  431. R. Takeno, Y. Okimura, G. Iguchi et al., “Intravenous administration of ghrelin stimulates growth hormone secretion in vagotomized patients as well as normal subjects,” European Journal of Endocrinology, vol. 151, no. 4, pp. 447–450, 2004. View at Publisher · View at Google Scholar · View at Scopus
  432. J. Saliba, J. Wattacheril, and N. N. Abumrad, “Endocrine and metabolic response to gastric bypass,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 12, no. 5, pp. 515–521, 2009. View at Publisher · View at Google Scholar · View at Scopus
  433. C. Maier, M. Riedl, G. Vila et al., “Cholinergic regulation of ghrelin and peptide YY release may be impaired in obesity,” Diabetes, vol. 57, no. 9, pp. 2332–2340, 2008. View at Publisher · View at Google Scholar · View at Scopus
  434. S. S. Qader, R. Hakanson, J. F. Rehfeld, I. Lundquist, and A. Salehi, “Proghrelin-derived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: a study on isolated islets from mouse and rat pancreas,” Regulatory Peptides, vol. 146, no. 1–3, pp. 230–237, 2008. View at Publisher · View at Google Scholar · View at Scopus
  435. M. Arosio, C. L. Ronchi, C. Gebbia, V. Cappiello, P. Beck-Peccoz, and M. Peracchi, “Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels,” The Journal of Clinical Endocrinology & Metabolism, vol. 88, no. 2, pp. 701–704, 2003. View at Publisher · View at Google Scholar · View at Scopus
  436. E. M. Egido, J. Rodriguez-Gallardo, R. A. Silvestre, and J. Marco, “Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion,” European Journal of Endocrinology, vol. 146, no. 2, pp. 241–244, 2002. View at Google Scholar · View at Scopus
  437. C. Cui, H. Ohnuma, M. Daimon et al., “Ghrelin infused into the portal vein inhibits glucose-stimulated insulin secretion in Wistar rats,” Peptides, vol. 29, no. 7, pp. 1241–1246, 2008. View at Publisher · View at Google Scholar · View at Scopus
  438. K. Dezaki, H. Sone, and T. Yada, “Ghrelin is a physiological regulator of insulin release in pancreatic islets and glucose homeostasis,” Pharmacology and Therapeutics, vol. 118, no. 2, pp. 239–249, 2008. View at Publisher · View at Google Scholar · View at Scopus
  439. K. Dezaki, M. Kakei, and T. Yada, “Ghrelin uses Gαi2 and activates voltage-dependent K+ channels to attenuate glucose-induced Ca2+ signaling and insulin release in islet β-cells: novel signal transduction of ghrelin,” Diabetes, vol. 56, no. 9, pp. 2319–2327, 2007. View at Publisher · View at Google Scholar · View at Scopus
  440. H. M. Lee, G. Wang, E. W. Englander, M. Kojima, and G. H. Greeley Jr., “Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations,” Endocrinology, vol. 143, no. 1, pp. 185–190, 2002. View at Publisher · View at Google Scholar · View at Scopus
  441. C. Gauna, R. M. Kiewiet, J. A. M. J. L. Janssen et al., “Unacylated ghrelin acts as a potent insulin secretagogue in glucose-stimulated conditions,” American Journal of Physiology, vol. 293, no. 3, pp. E697–E704, 2007. View at Publisher · View at Google Scholar · View at Scopus
  442. H. Kageyama, H. Funahashi, M. Hirayama et al., “Morphological analysis of ghrelin and its receptor distribution in the rat pancreas,” Regulatory Peptides, vol. 126, no. 1-2, pp. 67–71, 2005. View at Publisher · View at Google Scholar · View at Scopus
  443. T. Yada, K. Dezaki, H. Sone et al., “Ghrelin regulates insulin release and glycemia: physiological role and therapeutic potential,” Current Diabetes Reviews, vol. 4, no. 1, pp. 18–23, 2008. View at Publisher · View at Google Scholar · View at Scopus
  444. K. Dezaki, H. Hosoda, M. Kakei et al., “Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating Ca2+ signaling in ß-cells: implication in the glycemic control in rodents,” Diabetes, vol. 53, no. 12, pp. 3142–3151, 2004. View at Publisher · View at Google Scholar · View at Scopus
  445. R. M. Kiewiet, M. O. van Aken, K. van der Weerd et al., “Effects of acute administration of acylated and unacylated ghrelin on glucose and insulin concentrations in morbidly obese subjects without overt diabetes,” European Journal of Endocrinology, vol. 161, no. 4, pp. 567–573, 2009. View at Publisher · View at Google Scholar · View at Scopus
  446. L. J. Fick, F. Cai, and D. D. Belsham, “Hypothalamic preproghrelin gene expression is repressed by insulin via both PI3-K/Akt and ERK1/2 MAPK pathways in immortalized, hypothalamic neurons,” Neuroendocrinology, vol. 89, no. 3, pp. 267–275, 2009. View at Publisher · View at Google Scholar · View at Scopus
  447. A. Ikezaki, H. Hosoda, K. Ito et al., “Fasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin, in obese children and adolescents,” Diabetes, vol. 51, no. 12, pp. 3408–3411, 2002. View at Google Scholar · View at Scopus
  448. U. Pagotto, A. Gambineri, V. Vicennati, M. L. Heiman, M. Tschop, and R. Pasquali, “Plasma ghrelin, obesity, and the polycystic ovary syndrome: correlation with insulin resistance and androgen levels,” The Journal of Clinical Endocrinology & Metabolism, vol. 87, no. 12, pp. 5625–5629, 2002. View at Publisher · View at Google Scholar · View at Scopus
  449. A. P. Goldstone, M. Patterson, N. Kalingag et al., “Fasting and postprandial hyperghrelinemia in Prader-Willi syndrome is partially explained by hypoinsulinemia, and is not due to peptide YY 3-36 deficiency or seen in hypothalamic obesity due to craniopharyngioma,” The Journal of Clinical Endocrinology & Metabolism, vol. 90, no. 5, pp. 2681–2690, 2005. View at Publisher · View at Google Scholar · View at Scopus
  450. M. Tauber, F. C. Auriol, P. Moulin, C. Molinas, V. Delagnes, and J. P. Salles, “Hyperghrelinemia is a common feature of Prader-Willi syndrome and pituitary stalk interruption: a pathophysiological hypothesis,” Hormone Research, vol. 62, no. 1, pp. 49–54, 2004. View at Publisher · View at Google Scholar · View at Scopus
  451. Y. H. Choe, Y. S. Sang, K.-H. Paik et al., “Increased density of ghrelin-expressing cells in the gastric fundus and body in Prader-Willi syndrome,” The Journal of Clinical Endocrinology & Metabolism, vol. 90, no. 9, pp. 5441–5445, 2005. View at Publisher · View at Google Scholar · View at Scopus
  452. K. M. Andralojc, A. Mercalli, K. W. Nowak et al., “Ghrelin-producing epsilon cells in the developing and adult human pancreas,” Diabetologia, vol. 52, no. 3, pp. 486–493, 2009. View at Publisher · View at Google Scholar · View at Scopus
  453. N. Wierup, H. Svensson, H. Mulder, and F. Sundler, “The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas,” Regulatory Peptides, vol. 107, no. 1–3, pp. 63–69, 2002. View at Publisher · View at Google Scholar · View at Scopus
  454. C. L. Prado, A. E. Pugh-Bernard, L. Elghazi, B. Sosa-Pineda, and L. Sussel, “Ghrelin cells replace insulin-producing β cells in two mouse models of pancreas development,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 9, pp. 2924–2929, 2004. View at Publisher · View at Google Scholar · View at Scopus
  455. R. Granata, F. Settanni, L. Biancone et al., “Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic ß-cells and human islets: involvement of 3', 5'-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-kinase/Akt signaling,” Endocrinology, vol. 148, no. 2, pp. 512–529, 2007. View at Publisher · View at Google Scholar · View at Scopus
  456. K. Dezaki, H. Sone, M. Koizumi et al., “Blockade of pancreatic islet-derived ghrelin enhances insulin secretion to prevent high-fat diet-induced glucose intolerance,” Diabetes, vol. 55, no. 12, pp. 3486–3493, 2006. View at Publisher · View at Google Scholar · View at Scopus
  457. H. A. Halem, J. E. Taylor, J. Z. Dong et al., “Novel analogs of ghrelin: physiological and clinical implications,” European Journal of Endocrinology, vol. 151, supplement 1, pp. S71–S75, 2004. View at Publisher · View at Google Scholar · View at Scopus
  458. R. Nogueiras, D. Perez-Tilve, K. E. Wortley, and M. Tschop, “Growth hormone secretagogue (ghrelin-) receptors—a complex drug target for the regulation of body weight,” CNS and Neurological Disorders: Drug Targets, vol. 5, no. 3, pp. 335–343, 2006. View at Publisher · View at Google Scholar · View at Scopus
  459. Y. Lin, K. Matsumura, M. Fukuhara, S. Kagiyama, K. Fujii, and M. Iida, “Ghrelin acts at the nucleus of the solitary tract to decrease arterial pressure in rats,” Hypertension, vol. 43, no. 5, pp. 977–982, 2004. View at Publisher · View at Google Scholar · View at Scopus
  460. N. Nagaya, M. Kojima, M. Uematsu et al., “Hemodynamic and hormonal effects of human ghrelin in healthy volunteers,” American Journal of Physiology, vol. 280, no. 5, pp. R1483–R1487, 2001. View at Google Scholar · View at Scopus
  461. X.-B. Xu, J.-J. Pang, J.-M. Cao et al., “GH-releasing peptides improve cardiac dysfunction and cachexia and suppress stress-related hormones and cardiomyocyte apoptosis in rats with heart failure,” American Journal of Physiology, vol. 289, no. 4, pp. H1643–H1651, 2005. View at Publisher · View at Google Scholar · View at Scopus
  462. K. Matsumura, T. Tsuchihashi, K. Fujii, I. Abe, and M. Iida, “Central ghrelin modulates sympathetic activity in conscious rabbits,” Hypertension, vol. 40, no. 5, pp. 694–699, 2002. View at Publisher · View at Google Scholar · View at Scopus
  463. U. A. Shinde, K. M. Desai, C. Yu, and V. Gopalakrishnan, “Nitric oxide synthase inhibition exaggerates the hypotensive response to ghrelin: role of calcium-activated potassium channels,” Journal of Hypertension, vol. 23, no. 4, pp. 779–784, 2005. View at Google Scholar · View at Scopus
  464. M. Enomoto, N. Nagaya, M. Uematsu et al., “Cardiovascular and hormonal effects of subcutaneous administration of ghrelin, a novel growth hormone-releasing peptide, in healthy humans,” Clinical Science, vol. 105, no. 4, pp. 431–435, 2003. View at Publisher · View at Google Scholar · View at Scopus
  465. B. Moazed, D. Quest, and V. Gopalakrishnan, “Des-acyl ghrelin fragments evoke endothelium-dependent vasodilatation of rat mesenteric vascular bed via activation of potassium channels,” European Journal of Pharmacology, vol. 604, no. 1–3, pp. 79–86, 2009. View at Publisher · View at Google Scholar · View at Scopus
  466. M. J. Kleinz, J. J. Maguire, J. N. Skepper, and A. P. Davenport, “Functional and immunocytochemical evidence for a role of ghrelin and des-octanoyl ghrelin in the regulation of vascular tone in man,” Cardiovascular Research, vol. 69, no. 1, pp. 227–235, 2006. View at Publisher · View at Google Scholar · View at Scopus
  467. M.-J. Yuan, C.-X. Huang, Y.-H. Tang et al., “A novel peptide ghrelin inhibits neural remodeling after myocardial infarction in rats,” European Journal of Pharmacology, vol. 618, no. 1–3, pp. 52–57, 2009. View at Publisher · View at Google Scholar · View at Scopus
  468. D. O. Schwenke, T. Tokudome, M. Shirai et al., “Exogenous ghrelin attenuates the progression of chronic hypoxia-induced pulmonary hypertension in conscious rats,” Endocrinology, vol. 149, no. 1, pp. 237–244, 2008. View at Publisher · View at Google Scholar · View at Scopus
  469. S. Marleau, M. Mulumba, D. Lamontagne, and H. Ong, “Cardiac and peripheral actions of growth hormone and its releasing peptides: relevance for the treatment of cardiomyopathies,” Cardiovascular Research, vol. 69, no. 1, pp. 26–35, 2006. View at Publisher · View at Google Scholar · View at Scopus
  470. H. Okumura, N. Nagaya, M. Enomoto, E. Nakagawa, H. Oya, and K. Kangawa, “Vasodilatory effect of ghrelin, an endogenous peptide from the stomach,” Journal of Cardiovascular Pharmacology, vol. 39, no. 6, pp. 779–783, 2002. View at Publisher · View at Google Scholar · View at Scopus
  471. K. E. Wiley and A. P. Davenport, “Comparison of vasodilators in human internal mammary artery: ghrelin is a potent physiological antagonist of endothelin-1,” British Journal of Pharmacology, vol. 136, no. 8, pp. 1146–1152, 2002. View at Publisher · View at Google Scholar · View at Scopus
  472. M. J. Iglesias, R. Pineiro, M. Blanco et al., “Growth hormone releasing peptide (ghrelin) is synthesized and secreted by cardiomyocytes,” Cardiovascular Research, vol. 62, no. 3, pp. 481–488, 2004. View at Publisher · View at Google Scholar · View at Scopus
  473. S. Gnanapavan, B. Kola, S. A. Bustin et al., “The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans,” Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 6, pp. 2988–2991, 2002. View at Publisher · View at Google Scholar · View at Scopus
  474. V. Bodart, M. Febbraio, A. Demers et al., “CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart,” Circulation Research, vol. 90, no. 8, pp. 844–849, 2002. View at Publisher · View at Google Scholar · View at Scopus
  475. M. J. Iglesias, A. Salgado, R. Pineiro et al., “Lack of effect of the ghrelin gene-derived peptide obestatin on cardiomyocyte viability and metabolism,” Journal of Endocrinological Investigation, vol. 30, no. 6, pp. 470–476, 2007. View at Google Scholar · View at Scopus
  476. M. Tesauro, F. Schinzari, M. Iantorno et al., “Ghrelin improves endothelial function in patients with metabolic syndrome,” Circulation, vol. 112, no. 19, pp. 2986–2992, 2005. View at Publisher · View at Google Scholar · View at Scopus
  477. F. Rossi, C. Bertone, S. Petricca, and V. Santiemma, “Ghrelin inhibits angiotensin II-induced migration of human aortic endothelial cells,” Atherosclerosis, vol. 192, no. 2, pp. 291–297, 2007. View at Publisher · View at Google Scholar · View at Scopus
  478. M. T. Conconi, B. Nico, D. Guidolin et al., “Ghrelin inhibits FGF-2-mediated angiogenesis in vitro and in vivo,” Peptides, vol. 25, no. 12, pp. 2179–2185, 2004. View at Publisher · View at Google Scholar · View at Scopus
  479. Z. Xu, S. Lin, W. Wu et al., “Ghrelin prevents doxorubicin-induced cardiotoxicity through TNF-alpha/NF-?B pathways and mitochondrial protective mechanisms,” Toxicology, vol. 247, no. 2-3, pp. 133–138, 2008. View at Publisher · View at Google Scholar · View at Scopus
  480. M. Zhang, F. Yuan, H. Liu, H. Chen, X. Qiu, and W. Fang, “Inhibition of proliferation and apoptosis of vascular smooth muscle cells by ghrelin,” Acta Biochimica et Biophysica Sinica, vol. 40, no. 9, pp. 769–776, 2008. View at Publisher · View at Google Scholar · View at Scopus
  481. C. J. Pemberton, H. Tokola, Z. Bagi et al., “Ghrelin induces vasoconstriction in the rat coronary vasculature without altering cardiac peptide secretion,” American Journal of Physiology, vol. 287, no. 4, pp. H1522–H1529, 2004. View at Publisher · View at Google Scholar · View at Scopus
  482. L. Chang, J. Zhao, G.-Z. Li et al., “Ghrelin protects myocardium from isoproterenol-induced injury in rats,” Acta Pharmacologica Sinica, vol. 25, no. 9, pp. 1131–1137, 2004. View at Google Scholar · View at Scopus
  483. A. Cittadini, L. Saldamarco, A. M. Marra et al., “Growth hormone deficiency in patients with chronic heart failure and beneficial effects of its correction,” Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 9, pp. 3329–3336, 2009. View at Publisher · View at Google Scholar · View at Scopus
  484. N. Nagaya, M. Uematsu, M. Kojima et al., “Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors,” Circulation, vol. 104, no. 17, pp. 2034–2038, 2001. View at Google Scholar · View at Scopus
  485. Y. Shimizu, N. Nagaya, T. Isobe et al., “Increased plasma ghrelin level in lung cancer cachexia,” Clinical Cancer Research, vol. 9, no. 2, pp. 774–778, 2003. View at Google Scholar · View at Scopus
  486. Y. J. Akashi, S. Palus, R. Datta et al., “No effects of human ghrelin on cardiac function despite profound effects on body composition in a rat model of heart failure,” International Journal of Cardiology, vol. 137, no. 3, pp. 267–275, 2009. View at Publisher · View at Google Scholar · View at Scopus
  487. D. Z. Dimitrova, D. N. Mihov, R. Wang et al., “Contractile effect of ghrelin on isolated guinea-pig renal arteries,” Vascular Pharmacology, vol. 47, no. 1, pp. 31–40, 2007. View at Publisher · View at Google Scholar · View at Scopus
  488. J. Bellone, E. Bartolotta, C. Sgattoni et al., “Hexarelin, a synthetic GH-releasing peptide, is a powerful stimulus of GH secretion in pubertal children and in adults but not in prepubertal children and in elderly subjects,” Journal of Endocrinological Investigation, vol. 21, no. 8, pp. 494–500, 1998. View at Google Scholar · View at Scopus
  489. C. Dornonville de la Cour, M. Bjorkqvist, A. K. Sandvik et al., “A-like cells in the rat stomach contain ghrelin and do not operate under gastrin control,” Regulatory Peptides, vol. 99, no. 2-3, pp. 141–150, 2001. View at Publisher · View at Google Scholar · View at Scopus
  490. Z. Zhao and T. Sakai, “Characteristic features of ghrelin cells in the gastrointestinal tract and the regulation of stomach ghrelin expression and production,” World Journal of Gastroenterology, vol. 14, no. 41, pp. 6306–6311, 2008. View at Publisher · View at Google Scholar · View at Scopus
  491. N. Wierup, M. Bjorkqvist, B. Westrom, S. Pierzynowski, F. Sundler, and K. Sjolund, “Ghrelin and motilin are cosecreted from a prominent endocrine cell population in the small intestine,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 9, pp. 3573–3581, 2007. View at Publisher · View at Google Scholar · View at Scopus
  492. M. Camilleri, A. Papathanasopoulos, and S. T. Odunsi, “Actions and therapeutic pathways of ghrelin for gastrointestinal disorders,” Nature Reviews Gastroenterology and Hepatology, vol. 6, no. 6, pp. 343–352, 2009. View at Publisher · View at Google Scholar · View at Scopus
  493. M. Kapica, M. Zabielska, I. Puzio et al., “Obestatin stimulates the secretion of pancreatic juice enzymes through a vagal pathway in anaesthetized rats—preliminary results,” Journal of Physiology and Pharmacology, vol. 58, supplement 3, pp. 123–130, 2007. View at Google Scholar · View at Scopus
  494. Y. Nishi, H. Hiejima, H. Hosoda et al., “Ingested medium-chain fatty acids are directly utilized for the acyl modification of ghrelin,” Endocrinology, vol. 146, no. 5, pp. 2255–2264, 2005. View at Publisher · View at Google Scholar · View at Scopus
  495. Y. Nishi, H. Hiejima, H. Mifune, T. Sato, K. Kangawa, and M. Kojima, “Developmental changes in the pattern of ghrelin's acyl modification and the levels of acyl-modified ghrelins in murine stomach,” Endocrinology, vol. 146, no. 6, pp. 2709–2715, 2005. View at Publisher · View at Google Scholar · View at Scopus
  496. X. Zhu, Y. Cao, K. Voodg, and D. F. Steiner, “On the processing of proghrelin to ghrelin,” Journal of Biological Chemistry, vol. 281, no. 50, pp. 38867–38870, 2006. View at Publisher · View at Google Scholar · View at Scopus
  497. H. Hosoda, M. Kojima, H. Matsuo, and K. Kangawa, “Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue,” Biochemical and Biophysical Research Communications, vol. 279, no. 3, pp. 909–913, 2000. View at Publisher · View at Google Scholar · View at Scopus
  498. C. Erlanson-Albertsson and A. Lindqvist, “Vagotomy and accompanying pyloroplasty down-regulates ghrelin mRNA but does not affect ghrelin secretion,” Regulatory Peptides, vol. 151, no. 1–3, pp. 14–18, 2008. View at Publisher · View at Google Scholar · View at Scopus
  499. N. Amole and S. Unniappan, “Fasting induces preproghrelin mRNA expression in the brain and gut of zebrafish, Danio rerio,” General and Comparative Endocrinology, vol. 161, no. 1, pp. 133–137, 2009. View at Publisher · View at Google Scholar · View at Scopus
  500. M. Arosio, C. L. Ronchi, P. Beck-Peccoz et al., “Effects of modified sham feeding on ghrelin levels in healthy human subjects,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 10, pp. 5101–5104, 2004. View at Publisher · View at Google Scholar · View at Scopus
  501. I. Depoortere, T. Thijs, L. Thielemans, P. Robberecht, and T. L. Peeters, “Interaction of the growth hormone-releasing peptides ghrelin and growth hormone-releasing peptide-6 with the motilin receptor in the rabbit gastric antrum,” Journal of Pharmacology and Experimental Therapeutics, vol. 305, no. 2, pp. 660–667, 2003. View at Publisher · View at Google Scholar · View at Scopus
  502. I. Depoortere, B. De Winter, T. Thijs, J. De Man, P. Pelckmans, and T. Peeters, “Comparison of the gastroprokinetic effects of ghrelin, GHRP-6 and motilin in rats in vivo and in vitro,” European Journal of Pharmacology, vol. 515, no. 1–3, pp. 160–168, 2005. View at Publisher · View at Google Scholar · View at Scopus
  503. L. Xu, I. Depoortere, C. Tomasetto et al., “Evidence for the presence of motilin, ghrelin, and the motilin and ghrelin receptor in neurons of the myenteric plexus,” Regulatory Peptides, vol. 124, no. 1–3, pp. 119–125, 2005. View at Publisher · View at Google Scholar · View at Scopus
  504. C. Olsson, J. D. Holbrook, G. Bompadre et al., “Identification of genes for the ghrelin and motilin receptors and a novel related gene in fish, and stimulation of intestinal motility in zebrafish (Danio rerio) by ghrelin and motilin,” General and Comparative Endocrinology, vol. 155, no. 1, pp. 217–226, 2008. View at Publisher · View at Google Scholar · View at Scopus
  505. K. Kudoh, C. Shibata, Y. Funayama et al., “The effect of growth hormone releasing peptide-2 on upper gastrointestinal contractile activity and food intake in conscious dogs,” Journal of Gastroenterology, vol. 44, no. 4, pp. 297–304, 2009. View at Publisher · View at Google Scholar · View at Scopus
  506. W.-C. Qiu, Z.-G. Wang, W.-G. Wang, J. Yan, and Q. Zheng, “Gastric motor effects of ghrelin and growth hormone releasing peptide 6 in diabetic mice with gastroparesis,” World Journal of Gastroenterology, vol. 14, no. 9, pp. 1419–1424, 2008. View at Publisher · View at Google Scholar · View at Scopus
  507. L. Trudel, C. Tomasetto, M. C. Rio et al., “Ghrelin/motilin-related peptide is a potent prokinetic to reverse gastric postoperative ileus in rat,” American Journal of Physiology, vol. 282, no. 6, pp. G948–G952, 2002. View at Google Scholar · View at Scopus
  508. F. Levin, T. Edholm, P. T. Schmidt et al., “Ghrelin stimulates gastric emptying and hunger in normal-weight humans,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 9, pp. 3296–3302, 2006. View at Publisher · View at Google Scholar · View at Scopus
  509. G. J. Sanger, S. M. Westaway, A. A. Barnes et al., “GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility,” Neurogastroenterology and Motility, vol. 21, no. 6, p. 657, 2009. View at Publisher · View at Google Scholar · View at Scopus
  510. H. Ariga, K. Tsukamoto, C. Chen, C. Mantyh, T. N. Pappas, and T. Takahashi, “Endogenous acyl ghrelin is involved in mediating spontaneous phase III-like contractions of the rat stomach,” Neurogastroenterology and Motility, vol. 19, no. 8, pp. 675–680, 2007. View at Publisher · View at Google Scholar · View at Scopus
  511. D. Ang, H. Nicolai, R. Vos et al., “Influence of ghrelin on the gastric accommodation reflex and on meal-induced satiety in man,” Neurogastroenterology and Motility, vol. 21, no. 5, pp. 528–533, 2009. View at Publisher · View at Google Scholar · View at Scopus
  512. C. D. R. Murray, N. M. Martin, M. Patterson et al., “Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study,” Gut, vol. 54, no. 12, pp. 1693–1698, 2005. View at Publisher · View at Google Scholar · View at Scopus
  513. F. Katagiri, H. Itoh, and M. Takeyama, “Effects of erythromycin on plasma gastrin, somatostatin, and motilin levels in healthy volunteers and postoperative cancer patients,” Biological and Pharmaceutical Bulletin, vol. 28, no. 7, pp. 1307–1310, 2005. View at Publisher · View at Google Scholar · View at Scopus
  514. J. Tack, “Prokinetics and fundic relaxants in upper functional GI disorders,” Current Opinion in Pharmacology, vol. 8, no. 6, pp. 690–696, 2008. View at Publisher · View at Google Scholar · View at Scopus
  515. L. Chang, J. Zhao, J. Yang, Z. Zhang, J. Du, and C. Tang, “Therapeutic effects of ghrelin on endotoxic shock in rats,” European Journal of Pharmacology, vol. 473, no. 2-3, pp. 171–176, 2003. View at Publisher · View at Google Scholar · View at Scopus
  516. K. Yakabi, J. Kawashima, and S. Kato, “Ghrelin and gastric acid secretion,” World Journal of Gastroenterology, vol. 14, no. 41, pp. 6334–6338, 2008. View at Publisher · View at Google Scholar · View at Scopus
  517. P. L. R. Andrews and G. J. Sanger, “Abdominal vagal afferent neurones: an important target for the treatment of gastrointestinal dysfunction,” Current Opinion in Pharmacology, vol. 2, no. 6, pp. 650–656, 2002. View at Publisher · View at Google Scholar · View at Scopus
  518. A. Inui, A. Asakawa, C. Y. Bowers et al., “Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ,” The FASEB Journal, vol. 18, no. 3, pp. 439–456, 2004. View at Publisher · View at Google Scholar · View at Scopus
  519. W. Wargin, H. Thomas, L. Clohs et al., “Contribution of protein binding to the pharmacokinetics of the ghrelin receptor agonist TZP-101 in healthy volunteers and adults with symptomatic gastroparesis: two randomized, double-blind studies and a binding profile study,” Clinical Drug Investigation, vol. 29, no. 6, pp. 409–418, 2009. View at Publisher · View at Google Scholar · View at Scopus
  520. N. Ejskjaer, E. T. Vestergaard, P. M. Hellstrom et al., “Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis,” Alimentary Pharmacology and Therapeutics, vol. 29, no. 11, pp. 1179–1187, 2009. View at Publisher · View at Google Scholar · View at Scopus
  521. M. Binn, C. Albert, A. Gougeon et al., “Ghrelin gastrokinetic action in patients with neurogenic gastroparesis,” Peptides, vol. 27, no. 7, pp. 1603–1606, 2006. View at Publisher · View at Google Scholar · View at Scopus
  522. P. Poitras, W. J. Polvino, and B. Rocheleau, “Gastrokinetic effect of ghrelin analog RC-1139 in the rat: effect on post-operative and on morphine induced ileus,” Peptides, vol. 26, no. 9, pp. 1598–1601, 2005. View at Publisher · View at Google Scholar · View at Scopus
  523. S. Asai, T. Katabami, N. Obi et al., “No ghrelin response to oral glucose in diabetes mellitus with gastroparesis,” Endocrine Journal, vol. 56, no. 1, pp. 79–87, 2009. View at Publisher · View at Google Scholar · View at Scopus
  524. I. A. Harsch, C. Koebnick, A. M. Tasi, E. G. Hahn, and P. C. Konturek, “Ghrelin and obestatin levels in type 2 diabetic patients with and without delayed gastric emptying,” Digestive Diseases and Sciences, vol. 54, no. 10, pp. 2161–2166, 2009. View at Publisher · View at Google Scholar · View at Scopus
  525. A. Dzaja, M. A. Dalal, H. Himmerich, M. Uhr, T. Pollmacher, and A. Schuld, “Sleep enhances nocturnal plasma ghrelin levels in healthy subjects,” American Journal of Physiology, vol. 286, no. 6, pp. E963–E967, 2004. View at Publisher · View at Google Scholar · View at Scopus
  526. M. Kluge, M. Gazea, P. Schussler et al., “Ghrelin increases slow wave sleep and stage 2 sleep and decreases stage 1 sleep and REM sleep in elderly men but does not affect sleep in elderly women,” Psychoneuroendocrinology, vol. 35, no. 2, pp. 297–304, 2010. View at Publisher · View at Google Scholar · View at Scopus
  527. A. Steiger, “Ghrelin and sleep-wake regulation,” American Journal of Physiology, vol. 292, no. 1, pp. R573–R574, 2007. View at Publisher · View at Google Scholar · View at Scopus
  528. M. Kluge, P. Schussler, P. Bleninger et al., “Ghrelin alone or co-administered with GHRH or CRH increases non-REM sleep and decreases REM sleep in young males,” Psychoneuroendocrinology, vol. 33, no. 4, pp. 497–506, 2008. View at Publisher · View at Google Scholar · View at Scopus
  529. J. C. Weikel, A. Wichniak, M. Ising et al., “Ghrelin promotes slow-wave sleep in humans,” American Journal of Physiology, vol. 284, no. 2, pp. E407–E415, 2003. View at Google Scholar · View at Scopus
  530. P. Schuessler, M. Uhr, M. Ising, D. Schmid, J. Weikel, and A. Steiger, “Nocturnal ghrelin levels—relationship to sleep EEG, the levels of growth hormone, ACTH and cortisol—and gender differences,” Journal of Sleep Research, vol. 14, no. 4, pp. 329–336, 2005. View at Publisher · View at Google Scholar · View at Scopus
  531. R.-M. Frieboes, I. A. Antonijevic, K. Held et al., “Hexarelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers,” Psychoneuroendocrinology, vol. 29, no. 7, pp. 851–860, 2004. View at Publisher · View at Google Scholar · View at Scopus
  532. L. M. Seoane, S. A. Tovar, D. Perez et al., “Orexin A suppresses in vivo GH secretion,” European Journal of Endocrinology, vol. 150, no. 5, pp. 731–736, 2004. View at Publisher · View at Google Scholar · View at Scopus
  533. K.-I. Takahashi, K. Chin, T. Akamizu et al., “Acylated ghrelin level in patients with OSA before and after nasal CPAP treatment,” Respirology, vol. 13, no. 6, pp. 810–816, 2008. View at Publisher · View at Google Scholar · View at Scopus
  534. A. F. Leite-Moreira, A. Rocha-Sousa, and T. Henriques-Coelho, “Cardiac, skeletal, and smooth muscle regulation by ghrelin,” Vitamins and Hormones, vol. 77, pp. 207–238, 2007. View at Publisher · View at Google Scholar · View at Scopus
  535. S. Nunes, C. Nogueira-Silva, E. Dias, R. S. Moura, and J. Correia-Pinto, “Ghrelin and obestatin: different role in fetal lung development?” Peptides, vol. 29, no. 12, pp. 2150–2158, 2008. View at Publisher · View at Google Scholar · View at Scopus
  536. S. W. Kim, S. J. Her, S. J. Park et al., “Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells,” Bone, vol. 37, no. 3, pp. 359–369, 2005. View at Publisher · View at Google Scholar · View at Scopus
  537. S. Hwang, M. Moon, S. Kim, L. Hwang, K. J. Ahn, and S. Park, “Neuroprotective effect of ghrelin is associated with decreased expression of prostate apoptosis response-4,” Endocrine Journal, vol. 56, no. 4, pp. 609–617, 2009. View at Publisher · View at Google Scholar · View at Scopus
  538. A. Delgado-Rubin de Celix, J. A. Chowen, J. Argente, and L. M. Frago, “Growth hormone releasing peptide-6 acts as a survival factor in glutamate-induced excitotoxicity,” Journal of Neurochemistry, vol. 99, no. 3, pp. 839–849, 2006. View at Publisher · View at Google Scholar · View at Scopus
  539. M. S. Kim, C. Y. Yoon, P. G. Jang et al., “The mitogenic and antiapoptotic actions of ghrelin in 3T3-L1 adipocytes,” Molecular Endocrinology, vol. 18, no. 9, pp. 2291–2301, 2004. View at Publisher · View at Google Scholar · View at Scopus
  540. P. Cassoni, E. Allia, T. Marrocco et al., “Ghrelin and cortistatin in lung cancer: expression of peptides and relaed receptors in human primary tumors and in vitro effect on the H345 small cell carcinoma cell line,” Journal of Endocrinological Investigation, vol. 29, no. 9, pp. 781–790, 2006. View at Google Scholar · View at Scopus
  541. P. N. Lau, K. B. S. Chow, C.-B. Chan, C. H. K. Cheng, and H. Wise, “The constitutive activity of the ghrelin receptor attenuates apoptosis via a protein kinase C-dependent pathway,” Molecular and Cellular Endocrinology, vol. 299, no. 2, pp. 232–239, 2009. View at Publisher · View at Google Scholar · View at Scopus
  542. H. Chung, E. Kim, D. H. Lee et al., “Ghrelin inhibits apoptosis in hypothalamic neuronal cells during oxygen-glucose deprivation,” Endocrinology, vol. 148, no. 1, pp. 148–159, 2007. View at Publisher · View at Google Scholar · View at Scopus
  543. J. B. Ammori, W.-Z. Zhang, J.-Y. Li, B.-X. Chai, and M. W. Mulholland, “Effects of ghrelin on neuronal survival in cells derived from dorsal motor nucleus of the vagus,” Surgery, vol. 144, no. 2, pp. 159–167, 2008. View at Publisher · View at Google Scholar · View at Scopus
  544. P. Cassoni, C. Ghe, T. Marrocco et al., “Expression of ghrelin and biological activity of specific receptors for ghrelin and des-acyl ghrelin in human prostate neoplasms and related cell lines,” European Journal of Endocrinology, vol. 150, no. 2, pp. 173–184, 2004. View at Publisher · View at Google Scholar · View at Scopus
  545. W. Wang, M. Andersson, B. M. Iresjo, C. Lonnroth, and K. Lundholm, “Effects of ghrelin on anorexia in tumor-bearing mice with eicosanoid-related cachexia,” International Journal of Oncology, vol. 28, no. 6, pp. 1393–1400, 2006. View at Google Scholar · View at Scopus
  546. T. Hanada, K. Toshinai, N. Kajimura et al., “Anti-cachectic effect of ghrelin in nude mice bearing human melanoma cells,” Biochemical and Biophysical Research Communications, vol. 301, no. 2, pp. 275–279, 2003. View at Publisher · View at Google Scholar · View at Scopus
  547. M. D. DeBoer, X. X. Zhu, P. Levasseur et al., “Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia,” Endocrinology, vol. 148, no. 6, pp. 3004–3012, 2007. View at Publisher · View at Google Scholar · View at Scopus
  548. J. M. Garcia and W. J. Polvino, “Effect on body weight and safety of RC-1291, a novel, orally available ghrelin mimetic and growth hormone secretagogue: results of a phase I, randomized, placebo-controlled, multiple-dose study in healthy volunteers,” Oncologist, vol. 12, no. 5, pp. 594–600, 2007. View at Publisher · View at Google Scholar · View at Scopus
  549. S. Perboni, C. Bowers, S. Kojima, A. Asakawa, and A. Inui, “Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluoruracil in colon cancer cell-bearing mice,” World Journal of Gastroenterology, vol. 14, no. 41, pp. 6303–6305, 2008. View at Publisher · View at Google Scholar · View at Scopus
  550. W. T. Chance, R. Dayal, L. A. Friend, I. Thomas, and S. Sheriff, “Continuous intravenous infusion of ghrelin does not stimulate feeding in tumor-bearing rats,” Nutrition and Cancer, vol. 60, no. 1, pp. 75–90, 2008. View at Publisher · View at Google Scholar · View at Scopus
  551. F. Strasser, T. A. Lutz, M. T. Maeder et al., “Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study,” British Journal of Cancer, vol. 98, no. 2, pp. 300–308, 2008. View at Publisher · View at Google Scholar · View at Scopus
  552. K. Zwirska-Korczala, M. Adamczyk-Sowa, P. Sowa et al., “Role of leptin, ghrelin, angiotensin II and orexins in 3T3 L1 preadipocyte cells proliferation and oxidative metabolism,” Journal of Physiology and Pharmacology, vol. 58, supplement 1, pp. 53–64, 2007. View at Google Scholar · View at Scopus
  553. S. Sangiao-Alvarellos, M. J. Vazquez, L. Varela et al., “Central ghrelin regulates peripheral lipid metabolism in a growth hormone-independent fashion,” Endocrinology, vol. 150, no. 10, pp. 4562–4574, 2009. View at Publisher · View at Google Scholar · View at Scopus
  554. V. Ott, M. Fasshauer, A. Dalski et al., “Direct peripheral effects of ghrelin include suppression of adiponectin expression,” Hormone and Metabolic Research, vol. 34, no. 11-12, pp. 640–645, 2002. View at Publisher · View at Google Scholar · View at Scopus
  555. K. Choi, S.-G. Roh, Y.-H. Hong et al., “The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis,” Endocrinology, vol. 144, no. 3, pp. 754–759, 2003. View at Publisher · View at Google Scholar · View at Scopus
  556. T. Yasuda, T. Masaki, T. Kakuma, and H. Yoshimatsu, “Centrally administered ghrelin suppresses sympathetic nerve activity in brown adipose tissue of rats,” Neuroscience Letters, vol. 349, no. 2, pp. 75–78, 2003. View at Publisher · View at Google Scholar · View at Scopus
  557. T. Tsubone, T. Masaki, I. Katsuragi, K. Tanaka, T. Kakuma, and H. Yoshimatsu, “Ghrelin regulates adiposity in white adipose tissue and UCP1 mRNA expression in brown adipose tissue in mice,” Regulatory Peptides, vol. 130, no. 1-2, pp. 97–103, 2005. View at Publisher · View at Google Scholar · View at Scopus
  558. H. Takahashi, Y. Kurose, Y. Suzuki et al., “Ghrelin differentially modulates the GH secretory response to GHRH between the fed and fasted states in sheep,” Domestic Animal Endocrinology, vol. 37, no. 1, pp. 55–60, 2009. View at Publisher · View at Google Scholar · View at Scopus
  559. T. Yasuda, T. Masaki, T. Kakuma, and H. Yoshimatsu, “Hypothalamic melanocortin system regulates sympathetic nerve activity in brown adipose tissue,” Experimental Biology and Medicine, vol. 229, no. 3, pp. 235–239, 2004. View at Google Scholar · View at Scopus
  560. T. Yasuda, T. Masaki, T. Kakuma et al., “Dual regulatory effects of orexins on sympathetic nerve activity innervating brown adipose tissue in rats,” Endocrinology, vol. 146, no. 6, pp. 2744–2748, 2005. View at Publisher · View at Google Scholar · View at Scopus
  561. T. Yasuda, T. Masaki, T. Sakata, and H. Yoshimatsu, “Hypothalamic neuronal histamine regulates sympathetic nerve activity and expression of uncoupling protein 1 mRNA in brown adipose tissue in rats,” Neuroscience, vol. 125, no. 3, pp. 535–540, 2004. View at Publisher · View at Google Scholar · View at Scopus
  562. M. Lopez, L. M. Seoane, S. Tovar, R. Nogueiras, C. Dieguez, and R. Senaris, “Orexin-A regulates growth hormone-releasing hormone mRNA content in a nucleus-specific manner and somatostatin mRNA content in a growth hormone-dependent fashion in the rat hypothalamus,” European Journal of Neuroscience, vol. 19, no. 8, pp. 2080–2088, 2004. View at Publisher · View at Google Scholar · View at Scopus
  563. E. Sondergaard, L. C. Gormsem, B. Nellemann, E. T. Vestergaard, J. S. Christiansen, and S. Nielsen, “Visceral fat mass is a strong predictor of circulating ghrelin levels in premenopausal women,” European Journal of Endocrinology, vol. 160, no. 3, pp. 375–379, 2009. View at Publisher · View at Google Scholar · View at Scopus
  564. J.-B. Soares, R. Roncon-Albuquerque Jr., and A. Leite-Moreira, “Ghrelin and ghrelin receptor inhibitors: agents in the treatment of obesity,” Expert Opinion on Therapeutic Targets, vol. 12, no. 9, pp. 1177–1189, 2008. View at Publisher · View at Google Scholar · View at Scopus
  565. N. Fukushima, R. Hanada, H. Teranishi et al., “Ghrelin directly regulates bone formation,” Journal of Bone and Mineral Research, vol. 20, no. 5, pp. 790–798, 2005. View at Publisher · View at Google Scholar · View at Scopus
  566. P. J. D. Delhanty, B. C. J. van der Eerden, M. van der Velde et al., “Ghrelin and unacylated ghrelin stimulate human osteoblast growth via mitogen-activated protein kinase (MAPK)/phosphoinositide 3-kinase (PI3K) pathways in the absence of GHS-R1a,” Journal of Endocrinology, vol. 188, no. 1, pp. 37–47, 2006. View at Publisher · View at Google Scholar · View at Scopus
  567. A. Asakawa, A. Inui, T. Kaga et al., “A role of ghrelin in neuroendocrine and behavioral responses to stress in mice,” Neuroendocrinology, vol. 74, no. 3, pp. 143–147, 2001. View at Publisher · View at Google Scholar · View at Scopus
  568. A. Kawakami, N. Okada, K. Rokkaku, K. Honda, S. Ishibashi, and T. Onaka, “Leptin inhibits and ghrelin augments hypothalamic noradrenaline release after stress,” Stress, vol. 11, no. 5, pp. 363–369, 2008. View at Publisher · View at Google Scholar · View at Scopus
  569. P. Maruna, R. Gurlich, and M. Rosicka, “Ghrelin as an acute-phase reactant during postoperative stress response,” Hormone and Metabolic Research, vol. 40, no. 6, pp. 404–409, 2008. View at Publisher · View at Google Scholar · View at Scopus
  570. M. Lutter, I. Sakata, S. Osborne-Lawrence et al., “The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress,” Nature Neuroscience, vol. 11, no. 7, pp. 752–753, 2008. View at Publisher · View at Google Scholar · View at Scopus
  571. A. M. Vergnano, F. Ferrini, C. Salio, L. Lossi, M. Baratta, and A. Merighi, “The gastrointestinal hormone ghrelin modulates inhibitory neurotransmission in deep laminae of mouse spinal cord dorsal horn,” Endocrinology, vol. 149, no. 5, pp. 2306–2312, 2008. View at Publisher · View at Google Scholar · View at Scopus
  572. L. Wang, N. R. Basa, A. Shaikh et al., “LPS inhibits fasted plasma ghrelin levels in rats: role of IL-1 and PGs and functional implications,” American Journal of Physiology, vol. 291, no. 4, pp. G611–G620, 2006. View at Publisher · View at Google Scholar · View at Scopus
  573. N. Hedayati, S. Annambhotla, J. Jiang et al., “Growth hormone-releasing peptide ghrelin inhibits homocysteine-induced endothelial dysfunction in porcine coronary arteries and human endothelial cells,” Journal of Vascular Surgery, vol. 49, no. 1, pp. 199–207, 2009. View at Publisher · View at Google Scholar · View at Scopus
  574. H. Zhao, G. Liu, Q. Wang et al., “Effect of ghrelin on human endothelial cells apoptosis induced by high glucose,” Biochemical and Biophysical Research Communications, vol. 362, no. 3, pp. 677–681, 2007. View at Publisher · View at Google Scholar · View at Scopus
  575. A. Li, G. Cheng, G. Zhu, and A. S. Tarnawski, “Ghrelin stimulates angiogenesis in human microvascular endothelial cells: implications beyond GH release,” Biochemical and Biophysical Research Communications, vol. 353, no. 2, pp. 238–243, 2007. View at Publisher · View at Google Scholar · View at Scopus
  576. N. Hattori, T. Saito, T. Yagyu, B.-H. Jiang, K. Kitagawa, and C. Inagaki, “GH, GH receptor, GH secretagogue receptor, and Ghrelin expression in human T cells, B cells, and neutrophils,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 9, pp. 4284–4291, 2001. View at Publisher · View at Google Scholar · View at Scopus
  577. M. Granado, T. Priego, A. I. Martin, M. A. Villanua, and A. Lopez-Calderon, “Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats,” American Journal of Physiology, vol. 288, no. 3, pp. E486–E492, 2005. View at Publisher · View at Google Scholar · View at Scopus
  578. T. Waseem, M. Duxbury, H. Ito, S. W. Ashley, and M. K. Robinson, “Exogenous ghrelin modulates release of pro-inflammatory and anti-inflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathways,” Surgery, vol. 143, no. 3, pp. 334–342, 2008. View at Publisher · View at Google Scholar · View at Scopus
  579. H. Himmerich and A. J. Sheldrick, “TNF-alpha and ghrelin: opposite effects on immune system, metabolism and mental health,” Protein & Peptide Letters,2010, In press.
  580. N. Hattori, “Expression, regulation and biological actions of growth hormone (GH) and ghrelin in the immune system,” Growth Hormone and IGF Research, vol. 19, no. 3, pp. 187–197, 2009. View at Publisher · View at Google Scholar · View at Scopus
  581. Y.-H. Youm, H. Yang, Y. Sun et al., “Deficient ghrelin receptor-mediated signaling compromises thymic stromal cell microenvironment by acceleratingthymic adiposity,” Journal of Biological Chemistry, vol. 284, no. 11, pp. 7068–7077, 2009. View at Publisher · View at Google Scholar · View at Scopus
  582. G.-G. Zhang, X. Teng, Y. Liu et al., “Inhibition of endoplasm reticulum stress by ghrelin protects against ischemia/reperfusion injury in rat heart,” Peptides, vol. 30, no. 6, pp. 1109–1116, 2009. View at Publisher · View at Google Scholar · View at Scopus
  583. E. El Eter, A. Al Tuwaijiri, H. Hagar, and M. Arafa, “In vivo and in vitro antioxidant activity of ghrelin: attenuation of gastric ischemic injury in the rat,” Journal of Gastroenterology and Hepatology, vol. 22, no. 11, pp. 1791–1799, 2007. View at Publisher · View at Google Scholar · View at Scopus
  584. A. Kawczynska-Drozdz, R. Olszanecki, J. Jawien et al., “Ghrelin inhibits vascular superoxide production in spontaneously hypertensive rats,” American Journal of Hypertension, vol. 19, no. 7, pp. 764–767, 2006. View at Publisher · View at Google Scholar · View at Scopus
  585. Z. Liu, Y. Yu, Y. Jiang, and J. Li, “Growth hormone increases circulating neutrophil activation and provokes lung microvascular injury in septic peritonitis rats,” Journal of Surgical Research, vol. 105, no. 2, pp. 195–199, 2002. View at Publisher · View at Google Scholar · View at Scopus
  586. M. Granado, A. I. Martin, M. Lopez-Menduina, A. Lopez-Calderon, and M. A. Villanua, “GH-releasing peptide-2 administration prevents liver inflammatory response in endotoxemia,” American Journal of Physiology, vol. 294, no. 1, pp. E131–E141, 2008. View at Publisher · View at Google Scholar · View at Scopus
  587. R. Wu, W. Dong, M. Zhou et al., “Ghrelin attenuates sepsis-induced acute lung injury and mortality in rats,” American Journal of Respiratory and Critical Care Medicine, vol. 176, no. 8, pp. 805–813, 2007. View at Publisher · View at Google Scholar · View at Scopus
  588. R. Wu, W. Dong, M. Zhou, X. Cui, S. H. Hank, and P. Wang, “Ghrelin improves tissue perfusion in severe sepsis via downregulation of endothelin-1,” Cardiovascular Research, vol. 68, no. 2, pp. 318–326, 2005. View at Publisher · View at Google Scholar · View at Scopus
  589. R. Wu, W. Dong, X. Qiang et al., “Orexigenic hormone ghrelin ameliorates gut barrier dysfunction in sepsis in rats,” Critical Care Medicine, vol. 37, no. 8, pp. 2421–2426, 2009. View at Publisher · View at Google Scholar · View at Scopus
  590. A. Chorny, P. Anderson, E. Gonzalez-Rey, and M. Delgado, “Ghrelin protects against experimental sepsis by inhibiting high-mobility group box 1 release and by killing bacteria,” Journal of Immunology, vol. 180, no. 12, pp. 8369–8377, 2008. View at Google Scholar · View at Scopus
  591. R. Takeda, H. Nishimatsu, E. Suzuki et al., “Ghrelin improves renal function in mice with ischemic acute renal failure,” Journal of the American Society of Nephrology, vol. 17, no. 1, pp. 113–121, 2006. View at Publisher · View at Google Scholar · View at Scopus
  592. M. D. DeBoer, X. Zhu, P. R. Levasseur et al., “Ghrelin treatment of chronic kidney disease: improvements in lean body mass and cytokine profile,” Endocrinology, vol. 149, no. 2, pp. 827–835, 2008. View at Publisher · View at Google Scholar · View at Scopus
  593. K. Wynne, K. Giannitsopoulou, C. J. Small et al., “Subcutaneous ghrelin enhances acute food intake in malnourished patients who receive maintenance peritoneal dialysis: a randomized, placebo-controlled trial,” Journal of the American Society of Nephrology, vol. 16, no. 7, pp. 2111–2118, 2005. View at Publisher · View at Google Scholar · View at Scopus
  594. S. Het, G. Ramlow, and O. T. Wolf, “A meta-analytic review of the effects of acute cortisol administration on human memory,” Psychoneuroendocrinology, vol. 30, no. 8, pp. 771–784, 2005. View at Publisher · View at Google Scholar · View at Scopus
  595. A. K. Arbeiter, R. Buscher, S. Petersenn, B. P. Hauffa, K. Mann, and P. F. Hoyer, “Ghrelin and other appetite-regulating hormones in paediatric patients with chronic renal failure during dialysis and following kidney transplantation,” Nephrology Dialysis Transplantation, vol. 24, no. 2, pp. 643–646, 2009. View at Publisher · View at Google Scholar · View at Scopus
  596. B. Kola, I. Farkas, M. Christ-Crain et al., “The orexigenic effect of ghrelin is mediated through central activation of the endogenous cannabinoid system,” PLoS ONE, vol. 3, no. 3, article e1797, 2008. View at Publisher · View at Google Scholar · View at Scopus
  597. G. Van den Berghe, F. de Zegher, C. Y. Bowers et al., “Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness,” Clinical Endocrinology, vol. 45, no. 3, pp. 341–351, 1996. View at Google Scholar · View at Scopus
  598. G. Van den Berghe, R. C. Baxter, F. Weekers et al., “The combined administration of GH-releasing peptide-2 (GHRP-2), TRH and GnRH to men with prolonged critical illness evokes superior endocrine and metabolic effects compared to treatment with GHRP-2 alone,” Clinical Endocrinology, vol. 56, no. 5, pp. 655–669, 2002. View at Publisher · View at Google Scholar · View at Scopus
  599. R. Wu, M. Zhou, P. Das et al., “Ghrelin inhibits sympathetic nervous activity in sepsis,” American Journal of Physiology, vol. 293, no. 6, pp. E1697–E1702, 2007. View at Publisher · View at Google Scholar · View at Scopus
  600. R. Wu, M. Zhou, X. Cui, H. H. Simms, and P. Wang, “Upregulation of cardiovascular ghrelin receptor occurs in the hyperdynamic phase of sepsis,” American Journal of Physiology, vol. 287, no. 3, pp. H1296–H1302, 2004. View at Publisher · View at Google Scholar · View at Scopus
  601. R. Wu, M. Zhou, X. Cui, H. H. Simms, and P. Wang, “Ghrelin clearance is reduced at the late stage of polymicrobial sepsis,” International Journal of Molecular Medicine, vol. 12, no. 5, pp. 777–781, 2003. View at Google Scholar · View at Scopus
  602. K. Proulx, T. P. Vahl, D. L. Drazen, S. C. Woods, and R. J. Seeley, “The effect of adrenalectomy on ghrelin secretion and orexigenic action,” Journal of Neuroendocrinology, vol. 17, no. 7, pp. 445–451, 2005. View at Publisher · View at Google Scholar · View at Scopus
  603. B. Otto, M. Tschop, W. Heldwein, A. F. H. Pfeiffer, and S. Diederich, “Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans,” European Journal of Endocrinology, vol. 151, no. 1, pp. 113–117, 2004. View at Publisher · View at Google Scholar · View at Scopus
  604. O. Gualillo, J. E. Caminos, M. Blanco et al., “Ghrelin, a novel placental-derived hormone,” Endocrinology, vol. 142, no. 2, pp. 788–794, 2001. View at Publisher · View at Google Scholar · View at Scopus
  605. H. Rubinfeld, M. Hadani, J. E. Taylor et al., “Novel ghrelin analogs with improved affinity for the GH secretagogue receptor stimulate GH and prolactin release from human pituitary cells,” European Journal of Endocrinology, vol. 151, no. 6, pp. 787–795, 2004. View at Publisher · View at Google Scholar · View at Scopus
  606. K. Nakahara, M. Nakagawa, Y. Baba et al., “Maternal ghrelin plays an important role in rat fetal development during pregnancy,” Endocrinology, vol. 147, no. 3, pp. 1333–1342, 2006. View at Publisher · View at Google Scholar · View at Scopus
  607. J. Fuglsang, P. Sandager, N. Moller, S. Fisker, J. Frystyk, and P. Ovesen, “Peripartum maternal and foetal ghrelin, growth hormones, IGFs and insulin interrelations,” Clinical Endocrinology, vol. 64, no. 5, pp. 502–509, 2006. View at Publisher · View at Google Scholar · View at Scopus
  608. J. Fuglsang, C. Skjaerbaek, U. Espelund et al., “Ghrelin and its relationship to growth hormones during normal pregnancy,” Clinical Endocrinology, vol. 62, no. 5, pp. 554–559, 2005. View at Publisher · View at Google Scholar · View at Scopus
  609. J. Fuglsang, F. F. Lauszus, S. Fisker, A. Flyvbjerg, and P. Ovesen, “Growth hormone binding protein and maternal body mass index in relation to placental growth hormone and insulin requirements during pregnancy in type 1 diabetic women,” Growth Hormone and IGF Research, vol. 15, no. 3, pp. 223–230, 2005. View at Publisher · View at Google Scholar · View at Scopus
  610. E. Palik, E. Baranyi, Z. Melczer et al., “Elevated serum acylated (biologically active) ghrelin and resistin levels associate with pregnancy-induced weight gain and insulin resistance,” Diabetes Research and Clinical Practice, vol. 76, no. 3, pp. 351–357, 2007. View at Publisher · View at Google Scholar · View at Scopus
  611. I. Yokota, S. Kitamura, H. Hosoda, Y. Kotani, and K. Kangawa, “Concentration of the n-octanoylated active form of ghrelin in fetal and neonatal circulation,” Endocrine Journal, vol. 52, no. 2, pp. 271–276, 2005. View at Publisher · View at Google Scholar · View at Scopus
  612. N. Bouhours-Nouet, F. Boux de Casson, S. Rouleau et al., “Maternal and cord blood ghrelin in the pregnancies of smoking mothers: possible markers of nutrient availability for the fetus,” Hormone Research, vol. 66, no. 1, pp. 6–12, 2006. View at Publisher · View at Google Scholar · View at Scopus
  613. E. Tham, J. Liu, S. Innis et al., “Acylated ghrelin concentrations are markedly decreased during pregnancy in mothers with and without gestational diabetes: relationship with cholinesterase,” American Journal of Physiology, vol. 296, no. 5, pp. E1093–E1100, 2009. View at Publisher · View at Google Scholar · View at Scopus
  614. F. de Zegher, B. Spitz, G. Van den Berghe et al., “Postpartum hyperprolactinemia and hyporesponsiveness of growth hormone (GH) to GH-releasing peptide,” Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 1, pp. 103–106, 1998. View at Publisher · View at Google Scholar · View at Scopus
  615. A. Abizaid, L. Schiavo, and S. Diano, “Hypothalamic and pituitary expression of ghrelin receptor message is increased during lactation,” Neuroscience Letters, vol. 440, no. 3, pp. 206–210, 2008. View at Publisher · View at Google Scholar · View at Scopus
  616. A. Kotunia and R. Zabielski, “Ghrelin in the postnatal development of the gastrointestinal tract,” Journal of Physiology and Pharmacology, vol. 57, supplement 5, pp. 97–111, 2006. View at Google Scholar · View at Scopus
  617. A. Dembinski, Z. Warzecha, P. Ceranowicz et al., “Variable effect of ghrelin administration on pancreatic development in young rats. role of insulin-like growth factor-1,” Journal of Physiology and Pharmacology, vol. 56, no. 4, pp. 555–570, 2005. View at Google Scholar · View at Scopus
  618. A. C. Martini, R. Fernandez-Fernandez, S. Tovar et al., “Comparative analysis of the effects of ghrelin and unacylated ghrelin on luteinizing hormone secretion in male rats,” Endocrinology, vol. 147, no. 5, pp. 2374–2382, 2006. View at Publisher · View at Google Scholar · View at Scopus
  619. R. Fernandez-Fernandez, V. M. Navarro, M. L. Barreiro et al., “Effects of chronic hyperghrelinemia on puberty onset and pregnancy outcome in the rat,” Endocrinology, vol. 146, no. 7, pp. 3018–3025, 2005. View at Publisher · View at Google Scholar · View at Scopus
  620. M. L. Barreiro, F. Gaytan, J. M. Castellano et al., “Ghrelin inhibits the proliferative activity of immature Leydig cells in vivo and regulates stem cell factor messenger ribonucleic acid expression in rat testis,” Endocrinology, vol. 145, no. 11, pp. 4825–4834, 2004. View at Publisher · View at Google Scholar · View at Scopus
  621. M. Furuta, T. Funabashi, and F. Kimura, “Intracerebroventricular administration of ghrelin rapidly suppresses pulsatile luteinizing hormone secretion in ovariectomized rats,” Biochemical and Biophysical Research Communications, vol. 288, no. 4, pp. 780–785, 2001. View at Publisher · View at Google Scholar · View at Scopus
  622. R. Fernandez-Fernandez, M. Tena-Sempere, V. M. Navarro et al., “Effects of ghrelin upon gonadotropin-releasing hormone and gonadotropin secretion in adult female rats: in vivo and in vitro studies,” Neuroendocrinology, vol. 82, no. 5-6, pp. 245–255, 2005. View at Publisher · View at Google Scholar · View at Scopus
  623. M. Tena-Sempere, “Ghrelin and reproduction: ghrelin as novel regulator of the gonadotropic axis,” Vitamins and Hormones, vol. 77, pp. 285–300, 2007. View at Publisher · View at Google Scholar · View at Scopus
  624. M. L. Barreiro and M. Tena-Sempere, “Ghrelin and reproduction: a novel signal linking energy status and fertility?” Molecular and Cellular Endocrinology, vol. 226, no. 1-2, pp. 1–9, 2004. View at Publisher · View at Google Scholar · View at Scopus
  625. N. R. Vulliemoz, E. Xiao, L. Xia-Zhang, J. Rivier, and M. Ferin, “Astressin B, a nonselective corticotropin-releasing hormone receptor antagonist, prevents the inhibitory effect of ghrelin on luteinizing hormone pulse frequency in the ovariectomized rhesus monkey,” Endocrinology, vol. 149, no. 3, pp. 869–874, 2008. View at Publisher · View at Google Scholar · View at Scopus
  626. M.-C. Lebrethon, A. Aganina, M. Fournier, A. Gerard, A. S. Parent, and J. P. Bourguignon, “Effects of in vivo and in vitro administration of ghrelin, leptin and neuropeptide mediators on pulsatile gonadotrophin-releasing hormone secretion from male rat hypothalamus before and after puberty,” Journal of Neuroendocrinology, vol. 19, no. 3, pp. 181–188, 2007. View at Publisher · View at Google Scholar · View at Scopus
  627. S. Forbes, X. F. Li, J. Kinsey-Jones, and K. O'Byrne, “Effects of ghrelin on Kisspeptin mRNA expression in the hypothalamic medial preoptic area and pulsatile luteinising hormone secretion in the female rat,” Neuroscience Letters, vol. 460, no. 2, pp. 143–147, 2009. View at Publisher · View at Google Scholar · View at Scopus
  628. F. Gaytan, M. L. Barreiro, J. E. Caminos et al., “Expression of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in normal human testis and testicular tumors,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 1, pp. 400–409, 2004. View at Publisher · View at Google Scholar · View at Scopus
  629. I. Viani, A. Vottero, F. Tassi et al., “Ghrelin inhibits steroid biosynthesis by cultured granulosa-lutein cells,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 4, pp. 1476–1481, 2008. View at Publisher · View at Google Scholar · View at Scopus
  630. J. Iqbal, Y. Kurose, B. Canny, and I. J. Clarke, “Effects of central infusion of ghrelin on food intake and plasma levels of growth hormone, luteinizing hormone, prolactin, and cortisol secretion in sheep,” Endocrinology, vol. 147, no. 1, pp. 510–519, 2006. View at Publisher · View at Google Scholar · View at Scopus
  631. J. E. Caminos, M. Tena-Sempere, F. Gaytan et al., “Expression of ghrelin in the cyclic and pregnant rat ovary,” Endocrinology, vol. 144, no. 4, pp. 1594–1602, 2003. View at Publisher · View at Google Scholar · View at Scopus
  632. F. Gaytan, M. L. Barreiro, L. K. Chopin et al., “Immunolocalization of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in the cyclic human ovary,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 2, pp. 879–887, 2003. View at Publisher · View at Google Scholar · View at Scopus
  633. N. Tawadros, L. A. Salamonsen, E. Dimitriadis, and C. Chen, “Facilitation of decidualization by locally produced ghrelin in the human endometrium,” Molecular Human Reproduction, vol. 13, no. 7, pp. 483–489, 2007. View at Publisher · View at Google Scholar · View at Scopus
  634. C. Du, Xilingaowa, G. Cao et al., “Expression of the orexigenic peptide ghrelin in the sheep ovary,” Domestic Animal Endocrinology, vol. 36, no. 2, pp. 89–98, 2009. View at Publisher · View at Google Scholar · View at Scopus
  635. C. I. Messini, K. Dafopoulos, N. Chalvatzas, P. Georgoulias, and I. E. Messinis, “Effect of ghrelin on gonadotrophin secretion in women during the menstrual cycle,” Human Reproduction, vol. 24, no. 4, pp. 976–981, 2009. View at Publisher · View at Google Scholar · View at Scopus
  636. A. V. Tsolakis, M. Stridsberg, L. Grimelius et al., “Ghrelin immunoreactive cells in gastric endocrine tumors and their relation to plasma ghrelin concentration,” Journal of Clinical Gastroenterology, vol. 42, no. 4, pp. 381–388, 2008. View at Publisher · View at Google Scholar · View at Scopus
  637. R. Wasko, M. Jaskula, M. Kotwicka et al., “The expression of ghrelin in somatotroph and other types of pituitary adenomas,” Neuroendocrinology Letters, vol. 29, no. 6, pp. 929–938, 2008. View at Google Scholar · View at Scopus
  638. H. K. White, C. D. Petrie, W. Landschulz et al., “Effects of an oral growth hormone secretagogue in older adults,” Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 4, pp. 1198–1206, 2009. View at Publisher · View at Google Scholar · View at Scopus
  639. Q. F. Xie, C. X. Wu, Q. Y. Meng, and N. Li, “Ghrelin and truncated ghrelin variant plasmid vectors administration into skeletal muscle augments long-term growth in rats,” Domestic Animal Endocrinology, vol. 27, no. 2, pp. 155–164, 2004. View at Publisher · View at Google Scholar · View at Scopus
  640. J. Svensson, J. P. Monson, T. Vetter et al., “Oral administration of the growth hormone secretagogue NN703 in adult patients with growth hormone deficiency,” Clinical Endocrinology, vol. 58, no. 5, pp. 572–580, 2003. View at Publisher · View at Google Scholar · View at Scopus
  641. B. Alaioubi, K. Mann, and S. Petersenn, “Diagnosis of growth hormone deficiency in adults: provocative testing with GHRP6 in comparison to the insulin tolerance test,” Hormone and Metabolic Research, vol. 41, no. 3, pp. 238–243, 2009. View at Publisher · View at Google Scholar · View at Scopus
  642. Y. Pazos, F. F. Casanueva, and J. P. Camina, “Basic aspects of ghrelin action,” Vitamins and Hormones, vol. 77, pp. 89–119, 2007. View at Publisher · View at Google Scholar · View at Scopus
  643. H. Kaiya, M. Kojima, H. Hosoda et al., “Amidated fish ghrelin: purification, cDNA cloning in the Japanese eel and its biological activity,” Journal of Endocrinology, vol. 176, no. 3, pp. 415–423, 2003. View at Publisher · View at Google Scholar · View at Scopus
  644. L. G. Riley, B. K. Fox, H. Kaiya, T. Hirano, and E. G. Grau, “Long-term treatment of ghrelin stimulates feeding, fat deposition, and alters the GH/IGF-I axis in the tilapia, Oreochromis mossambicus,” General and Comparative Endocrinology, vol. 142, no. 1-2, pp. 234–240, 2005. View at Publisher · View at Google Scholar · View at Scopus
  645. E. A. Garcia, B. Heude, C. J. Petry et al., “Ghrelin receptor gene polymorphisms and body size in children and adults,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 10, pp. 4158–4161, 2008. View at Publisher · View at Google Scholar · View at Scopus
  646. A. Baessler, M. Fischer, B. Mayer et al., “Epistatic interaction between haplotypes of the ghrelin ligand and receptor genes influence susceptibility to myocardial infarction and coronary artery disease,” Human Molecular Genetics, vol. 16, no. 8, pp. 887–899, 2007. View at Publisher · View at Google Scholar · View at Scopus
  647. W.-J. Li, Y.-S. Zhen, K. Sun et al., “Ghrelin receptor gene polymorphisms are associated with female metabolic syndrome in Chinese population,” Chinese Medical Journal, vol. 121, no. 17, pp. 1666–1669, 2008. View at Google Scholar · View at Scopus
  648. M. Korbonits, M. Gueorguiev, E. O'Grady et al., “A variation in the ghrelin gene increases weight and decreases insulin secretion in tall, obese children,” Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 8, pp. 4005–4008, 2002. View at Publisher · View at Google Scholar · View at Scopus
  649. A. Ozawa, Y. Cai, and I. Lindberg, “Production of bioactive peptides in an in vitro system,” Analytical Biochemistry, vol. 366, no. 2, pp. 182–189, 2007. View at Publisher · View at Google Scholar · View at Scopus
  650. T. Takahashi, T. Ida, T. Sato et al., “Production of n-octanoyl-modified ghrelin in cultured cells requires prohormone processing protease and ghrelin o-acyltransferase, as well as n-octanoic acid,” Journal of Biochemistry, vol. 146, no. 5, pp. 675–682, 2009. View at Publisher · View at Google Scholar · View at Scopus
  651. Y. Yang, J. Cao, and Y. Shi, “Identification and characterization of a gene encoding human LPGAT1, an endoplasmic reticulum-associated lysophosphatidylglycerol acyltransferase,” Journal of Biological Chemistry, vol. 279, no. 53, pp. 55866–55874, 2004. View at Publisher · View at Google Scholar · View at Scopus
  652. J. LeSautera, N. Hoque, M. Weintraub, D. W. Pfaff, and R. Silver, “Stomach ghrelin-secreting cells as food-entrainable circadian clocks,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 32, pp. 13582–13587, 2009. View at Publisher · View at Google Scholar · View at Scopus
  653. K. A. Bennett, C. J. Langmead, A. Wise, and G. Milligan, “Growth hormone secretagogues and growth hormone releasing peptides act as orthosteric super-agonists but not allosteric regulators for activation of the G protein Gαo1 by the ghrelin receptor,” Molecular Pharmacology, vol. 76, no. 4, pp. 802–811, 2009. View at Publisher · View at Google Scholar · View at Scopus
  654. G. S. Tannenbaum, Z. J. Khoja, J.-K. Chang, J. D. Veldhuis, and C. Y. Bowers, “In vivo activity of in vitro ghrelin O-acyltransferase (GOAT) inhibitors on food intake and GH release in rats,” in Proceedings of the 91st Annual Meeting of the Endocrine Society, Washington, DC, USA, 2009.