Table of Contents Author Guidelines Submit a Manuscript
International Journal of Endocrinology
Volume 2013 (2013), Article ID 684659, 8 pages
http://dx.doi.org/10.1155/2013/684659
Research Article

Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons

1Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
2Section of Sexual Medicine and Andrology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy
3Centro Interuniversitario di Ricerca sulle Basi Molecolari della Malattie della Riproduzione (CIRMAR), 20122 Milan, Italy

Received 13 November 2013; Revised 13 December 2013; Accepted 18 December 2013

Academic Editor: Amelie Bonnefond

Copyright © 2013 Annamaria Morelli et al. 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. M. Schwanzel-Fukuda, “Origin and migration of luteinizing hormone-releasing hormone neurons in mammals,” Microscopy Research and Technique, vol. 44, no. 1, pp. 2–10, 1999. View at Google Scholar
  2. S. Wray, “Development of gonadotropin-releasing hormone-1 neurons,” Frontiers in Neuroendocrinology, vol. 23, no. 3, pp. 292–316, 2002. View at Publisher · View at Google Scholar · View at Scopus
  3. A. E. Herbison, “Physiology of the gonadotropin-releasing hormone neuronal network,” in Physiology of Reproduction, E. Knobil and J. D. Neill, Eds., pp. 1415–1482, Raven Press, New York, NY, USA, 3rd edition, 2006. View at Google Scholar
  4. M. K. Herde, K. Geist, R. E. Campbell, and A. E. Herbison, “Gonadotropin-releasing hormone neurons extend complex highly branched dendritic trees outside the blood-brain barrier,” Endocrinology, vol. 152, no. 10, pp. 3832–3841, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. R. Fernandez-Fernandez, A. C. Martini, V. M. Navarro et al., “Novel signals for the integration of energy balance and reproduction,” Molecular and Cellular Endocrinology, vol. 254-255, pp. 127–132, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. J. T. George, R. P. Millar, and R. A. Anderson, “Hypothesis: kisspeptin mediates male hypogonadism in obesity and type 2 diabetes,” Neuroendocrinology, vol. 91, no. 4, pp. 302–307, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. J. M. Castellano and M. Tena-Sempere, “Metabolic regulation of kisspeptin,” Advances in Experimental Medicine and Biology, vol. 784, pp. 363–383, 2013. View at Google Scholar
  8. L. Pinilla, E. Aguilar, C. Dieguez, R. P. Millar, and M. Tena-Sempere, “Kisspeptins and reproduction: physiological roles and regulatory mechanisms,” Physiological Reviews, vol. 92, no. 3, pp. 1235–1316, 2012. View at Google Scholar
  9. J. Buvat, M. Maggi, A. Guay, and L. O. Torres, “Testosterone deficiency in men: systematic review and standard operating procedures for diagnosis and treatment,” Journal of Sexual Medicine, vol. 10, no. 1, pp. 245–284, 2013. View at Google Scholar
  10. S. Dhindsa, M. G. Miller, C. L. McWhirter et al., “Testosterone concentrations in diabetic and nondiabetic obese men,” Diabetes Care, vol. 33, no. 6, pp. 1186–1192, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. D. Kapoor, H. Aldred, S. Clark, K. S. Channer, and T. H. Jones, “Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes: correlations with bioavailable testosterone and visceral adiposity,” Diabetes Care, vol. 30, no. 4, pp. 911–917, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Grossmann, M. C. Thomas, S. Panagiotopoulos et al., “Low testosterone levels are common and associated with insulin resistance in men with diabetes,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 5, pp. 1834–1840, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. S. Dhindsa, S. Prabhakar, M. Sethi, A. Bandyopadhyay, A. Chaudhuri, and P. Dandona, “Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 11, pp. 5462–5468, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. G. Corona, E. Mannucci, L. Petrone et al., “Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic,” International Journal of Impotence Research, vol. 18, no. 2, pp. 190–197, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. P. Dandona and S. Dhindsa, “Update: hypogonadotropic hypogonadism in type 2 diabetes and obesity,” Journal of Clinical Endocrinology and Metabolism, vol. 96, no. 9, pp. 2643–2651, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. D. Tripathy, S. Dhindsa, R. Garg, A. Khaishagi, T. Syed, and P. Dandona, “Hypogonadotropic hypogonadism in erectile dysfunction associated with type 2 diabetes mellitus: a common defect?” Metabolic Syndrome and Related Disorders, vol. 1, no. 1, pp. 75–80, 2003. View at Google Scholar
  17. N. Pitteloud, M. Hardin, A. A. Dwyer et al., “Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 5, pp. 2636–2641, 2005. View at Publisher · View at Google Scholar · View at Scopus
  18. P. R. Costanzo, S. M. Suarez, H. E. Scaglia, C. Zylbersztein, L. E. Litwak, and P. Knoblovits, “Evaluation of the hypothalamic-pituitary-gonadal axis in eugonadal men with type 2 diabetes mellitus,” Andrology, vol. 2, no. 1, pp. 117–124, 2014. View at Publisher · View at Google Scholar
  19. G. Corona, E. Mannucci, G. Forti, and M. Maggi, “Hypogonadism, ED, metabolic syndrome and obesity: a pathological link supporting cardiovascular diseases,” International Journal of Andrology, vol. 32, no. 6, pp. 587–598, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Filippi, L. Vignozzi, A. Morelli et al., “Testosterone partially ameliorates metabolic profile and erectile responsiveness to PDE5 inhibitors in an animal model of male metabolic syndrome,” Journal of Sexual Medicine, vol. 6, no. 12, pp. 3274–3288, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Morelli, E. Sarchielli, P. Comeglio et al., “Metabolic syndrome induces inflammation and impairs gonadotropin-releasing hormone neurons in the preoptic area of the hypothalamus in rabbits,” Molecular and Cellular Endocrinology, vol. 382, no. 1, pp. 107–119, 2014. View at Google Scholar
  22. G. B. Vannelli, F. Ensoli, R. Zonefrati et al., “Neuroblast long-term cell cultures from human fetal olfactory epithelium respond to odors,” Journal of Neuroscience, vol. 15, no. 6, pp. 4382–4394, 1995. View at Google Scholar · View at Scopus
  23. T. Barni, M. Maggi, G. Fantoni et al., “Sex steroids and odorants modulate gonadotropin-releasing hormone secretion in primary cultures of human olfactory cells,” Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 11, pp. 4266–4273, 1999. View at Google Scholar · View at Scopus
  24. M. Maggi, T. Barni, G. Fantoni et al., “Expression and biological effects of endothelin-1 in human gonadotropin-releasing hormone-secreting neurons,” Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 4, pp. 1658–1665, 2000. View at Publisher · View at Google Scholar · View at Scopus
  25. A. Morelli, M. Marini, R. Mancina et al., “Sex steroids and leptin regulate the “first kiss” (KiSS 1/g-protein-coupled receptor 54 system) in human gonadotropin-releasing-hormone-secreting neuroblasts,” Journal of Sexual Medicine, vol. 5, no. 5, pp. 1097–1113, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Morelli, B. Fibbi, M. Marini et al., “Dihydrotestosterone and leptin regulate gonadotropin-releasing hormone (GnRH) expression and secretion in human GnRH-secreting neuroblasts,” Journal of Sexual Medicine, vol. 6, no. 2, pp. 397–407, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. X.-H. Zhang, A. Morelli, M. Luconi et al., “Testosterone regulates PDE5 expression and in vivo responsiveness to tadalafil in rat corpus cavernosum,” European Urology, vol. 47, no. 3, pp. 409–416, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. A. V. Roland and S. M. Moenter, “Regulation of gonadotropin-releasing hormone neurons by glucose,” Trends in Endocrinology and Metabolism, vol. 22, no. 11, pp. 443–449, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. C. Zhang, M. A. Bosch, J. E. Levine, O. K. Rønnekleiv, and M. J. Kelly, “Gonadotropin-releasing hormone neurons express KATP channels that are regulated by estrogen and responsive to glucose and metabolic inhibition,” Journal of Neuroscience, vol. 27, no. 38, pp. 10153–10164, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. C. Beall, D. L. Hamilton, J. Gallagher et al., “Mouse hypothalamic GT1-7 cells demonstrate AMPK-dependent intrinsic glucose-sensing behavior,” Diabetologia, vol. 55, no. 9, pp. 2432–2444, 2012. View at Google Scholar
  31. A. V. Roland and S. M. Moenter, “Glucosensing by GnRH neurons: inhibition by androgens and involvement of AMP-activated protein kinase,” Molecular Endocrinology, vol. 25, no. 5, pp. 847–858, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. S. A. McFadden, J. A. Menchella, J. A. Chalmers, M. L. Centeno ML, and D. D. Belsham, “Glucose responsiveness in a novel adult-derived GnRH cell line, mHypoA-GnRH/GFP: involvement of AMP-activated protein kinase,” Molecular and Cellular Endocrinology, vol. 377, no. 1-2, pp. 65–74, 2013. View at Google Scholar
  33. R. G. Romanelli, T. Barni, M. Maggi et al., “Expression and function of gonadotropin-releasing hormone (GnRH) receptor in human olfactory GnRH-secreting neurons: an autocrine GnRH loop underlies neuronal migration,” Journal of Biological Chemistry, vol. 279, no. 1, pp. 117–126, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. R. G. Romanelli, T. Barni, M. Maggi et al., “Role of endothelin-1 in the migration of human olfactory gonadotropin-releasing hormone-secreting neuroblasts,” Endocrinology, vol. 146, no. 10, pp. 4321–4330, 2005. View at Publisher · View at Google Scholar · View at Scopus
  35. D. González-Martínez, S.-H. Kim, Y. Hu et al., “Anosmin-1 modulates fibroblast growth factor receptor 1 signaling in human gonadotropin-releasing hormone olfactory neuroblasts through a heparan sulfate-dependent mechanism,” Journal of Neuroscience, vol. 24, no. 46, pp. 10384–10392, 2004. View at Publisher · View at Google Scholar · View at Scopus
  36. Y. Hu, S. Poopalasundaram, A. Graham, and P. M. Bouloux, “GnRH neuronal migration and olfactory bulb neurite outgrowth are dependent on FGF receptor 1 signaling, specifically via the PI3K p110alpha isoform in chick embryo,” Endocrinology, vol. 154, no. 1, pp. 388–399, 2013. View at Google Scholar
  37. S. Giannini, S. Benvenuti, P. Luciani et al., “Intermittent high glucose concentrations reduce neuronal precursor survival by altering the IGF system: the involvement of the neuroprotective factor DHCR24 (Seladin-1),” Journal of Endocrinology, vol. 198, no. 3, pp. 523–532, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. P. L. Mellon, J. J. Windle, P. C. Goldsmith, C. A. Padula, J. L. Roberts, and R. I. Weiner, “Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis,” Neuron, vol. 5, no. 1, pp. 1–10, 1990. View at Publisher · View at Google Scholar · View at Scopus
  39. T. Terasaka, F. Otsuka, N. Tsukamoto et al., “Mutual interaction of kisspeptin, estrogen and bone morphogenetic protein-4 activity in GnRH regulation by GT1-7 cells,” Molecular and Cellular Endocrinology, vol. 381, no. 1-2, pp. 8–15, 2013. View at Google Scholar
  40. N. Pitteloud, A. Meysing, R. Quinton et al., “Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes,” Molecular and Cellular Endocrinology, vol. 254-255, pp. 60–69, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Cariboni, J. Hickok, S. Rakic et al., “Neuropilins and their ligands are important in the migration of gonadotropin-releasing hormone neurons,” Journal of Neuroscience, vol. 27, no. 9, pp. 2387–2395, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. S. D. Noel, K. L. Keen, D. I. Baumann, E. J. Filardo, and E. Terasawa, “Involvement of G protein-coupled receptor 30 (GPR30) in rapid action of estrogen in primate LHRH neurons,” Molecular Endocrinology, vol. 23, no. 3, pp. 349–359, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. J. Sun, Z. Chu, and S. M. Moenter, “Diurnal in vivo and rapid in vitro effects of estradiol on voltage-gated calcium channels in gonadotropin-releasing hormone neurons,” Journal of Neuroscience, vol. 30, no. 11, pp. 3912–3923, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. H. J. Billings, J. M. Connors, S. N. Altman et al., “Neurokinin B acts via the neurokinin-3 receptor in the retrochiasmatic area to stimulate luteinizing hormone secretion in sheep,” Endocrinology, vol. 151, no. 8, pp. 3836–3846, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Amstalden, L. M. Coolen, A. M. Hemmerle et al., “Neurokinin 3 receptor immunoreactivity in the septal region, preoptic area and hypothalamus of the female sheep: colocalisation in neurokinin B cells of the arcuate nucleus but not in gonadotrophin-releasing hormone neurones,” Journal of Neuroendocrinology, vol. 22, no. 1, pp. 1–12, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. V. M. Navarro, M. L. Gottsch, M. Wu et al., “Regulation of NKB pathways and their roles in the control of Kiss1 neurons in the arcuate nucleus of the male mouse,” Endocrinology, vol. 152, no. 11, pp. 4265–4275, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. J. Young, J. T. George, J. A. Tello et al., “Kisspeptin restores pulsatile LH secretion in patients with neurokinin B signaling deficiencies: physiological, pathophysiological and therapeutic implications,” Neuroendocrinology, vol. 97, no. 2, pp. 193–202, 2013. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Gamba and F. P. Pralong, “Control of GnRH neuronal activity by metabolic factors: the role of leptin and insulin,” Molecular and Cellular Endocrinology, vol. 254-255, pp. 133–139, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. M. J. Cunningham, D. K. Clifton, and R. A. Steiner, “Leptin's actions on the reproductive axis: perspectives and mechanisms,” Biology of Reproduction, vol. 60, no. 2, pp. 216–222, 1999. View at Publisher · View at Google Scholar · View at Scopus
  50. P. Magni, R. Vettor, C. Pagano et al., “Expression of a leptin receptor in immortalized gonadotropin-releasing hormone-secreting neurons,” Endocrinology, vol. 140, no. 4, pp. 1581–1585, 1999. View at Google Scholar · View at Scopus