Table of Contents
Advances in Biology
Volume 2014 (2014), Article ID 512650, 10 pages
http://dx.doi.org/10.1155/2014/512650
Review Article

Effects of the Hormone Kisspeptin on Reproductive Hormone Release in Humans

Department of Investigative Medicine, Imperial College London, London W12 ONN, UK

Received 31 March 2014; Accepted 9 July 2014; Published 5 August 2014

Academic Editor: Paul Rösch

Copyright © 2014 Joanne L. Calley and Waljit S. Dhillo. 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. Kotani, M. Detheux, A. Vandenbogaerde et al., “The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54,” The Journal of Biological Chemistry, vol. 276, no. 37, pp. 34631–34636, 2001. View at Publisher · View at Google Scholar · View at Scopus
  2. J. H. Lee, M. E. Miele, D. J. Hicks et al., “KiSS-1, a novel human malignant melanoma metastasis-suppressor gene,” Journal of the National Cancer Institute, vol. 88, no. 23, pp. 1731–1737, 1996. View at Publisher · View at Google Scholar · View at Scopus
  3. T. Ohtaki, Y. Shintani, S. Honda et al., “Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor,” Nature, vol. 411, no. 6837, pp. 613–617, 2001. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Abbara, R. Ratnasabapathy, C. N. Jayasena, and W. S. Dhillo, “The effects of kisspeptin on gonadotropin release in non-human mammals,” Advances in Experimental Medicine and Biology, vol. 784, pp. 63–87, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. W. S. Dhillo, O. B. Chaudhri, M. Patterson et al., “Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 12, pp. 6609–6615, 2005. View at Publisher · View at Google Scholar · View at Scopus
  6. C. N. Jayasena, G. M. K. Nijher, A. Abbara et al., “Twice-weekly administration of kisspeptin-54 for 8 weeks stimulates release of reproductive hormones in women with hypothalamic amenorrhea,” Clinical Pharmacology and Therapeutics, vol. 88, no. 6, pp. 840–847, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. J. T. George, J. D. Veldhuis, A. K. Roseweir et al., “Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men,” The Journal of Clinical Endocrinology and Metabolism, vol. 96, no. 8, pp. E1228–E1236, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. C. N. Jayasena, G. M. K. Nijher, A. N. Comninos et al., “The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans,” The Journal of Clinical Endocrinology & Metabolism, vol. 96, no. 12, pp. E1963–E1972, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. Y. M. Chan, J. P. Butler, V. F. Sidhoum, N. E. Pinnell, and S. B. Seminara, “Kisspeptin administration to women: a window into endogenous kisspeptin secretion and GnRH responsiveness across the menstrual cycle,” Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 8, pp. E1458–E1467, 2012. View at Publisher · View at Google Scholar · View at Scopus
  10. C. N. Jayasena, A. N. Comninos, J. D. Veldhuis et al., “A single injection of kisspeptin-54 temporarily increases luteinizing hormone pulsatility in healthy women,” Clinical Endocrinology, vol. 79, no. 4, pp. 558–563, 2013. View at Publisher · View at Google Scholar
  11. W. S. Dhillo, O. B. Chaudhri, E. L. Thompson et al., “Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 10, pp. 3958–3966, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. C. N. Jayasena, G. M. K. Nijher, O. B. Chaudhri et al., “Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis,” Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 11, pp. 4315–4323, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. J. T. George, J. D. Veldhuis, M. Tena-Sempere, R. P. Millar, and R. A. Anderson, “Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: Kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism,” Clinical Endocrinology, vol. 79, no. 1, pp. 100–104, 2013. View at Publisher · View at Google Scholar · View at Scopus
  14. J. T. George, R. A. Anderson, and R. P. Millar, “Kisspeptin-10 stimulation of gonadotrophin secretion in women is modulated by sex steroid feedback,” Human Reproduction, vol. 27, no. 12, pp. 3552–3559, 2012. View at Publisher · View at Google Scholar · View at Scopus
  15. 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
  16. C. N. Jayasena, A. N. Comninos, G. M. K. Nijher et al., “Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual cyclicity in healthy female volunteers,” Journal of Clinical Endocrinology & Metabolism, vol. 98, pp. 4464–4474, 2013. View at Google Scholar
  17. Y.-M. Chan, J. P. Butler, N. E. Pinnell et al., “Kisspeptin resets the hypothalamic GnRH clock in men,” Journal of Clinical Endocrinology and Metabolism, vol. 96, no. 6, pp. E908–E915, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. G. M. K. Nijher, O. B. Chaudhri, R. Ramachandran et al., “The effects of kisspeptin-54 on blood pressure in humans and plasma kisspeptin concentrations in hypertensive diseases of pregnancy,” The British Journal of Clinical Pharmacology, vol. 70, no. 5, pp. 674–681, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. M. L. Gottsch, M. J. Cunningham, J. T. Smith et al., “A role for kisspeptins in the regulation of gonadotropin secretion in the mouse,” Endocrinology, vol. 145, no. 9, pp. 4073–4077, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. S. D. C. Bianco and U. B. Kaiser, “The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism,” Nature Reviews Endocrinology, vol. 5, no. 10, pp. 569–576, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. L. F. G. Silveira and A. C. Latronico, “Approach to the patient with hypogonadotropic hypogonadism,” The Journal of Clinical Endocrinology & Metabolism, vol. 98, no. 5, pp. 1781–1788, 2013. View at Publisher · View at Google Scholar · View at Scopus
  22. D. K. Lee, T. Nguyen, G. P. O'Neill et al., “Discovery of a receptor related to the galanin receptors,” The FEBS Letters, vol. 446, no. 1, pp. 103–107, 1999. View at Publisher · View at Google Scholar · View at Scopus
  23. Y. Horikoshi, H. Matsumoto, Y. Takatsu et al., “Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 2, pp. 914–919, 2003. View at Publisher · View at Google Scholar · View at Scopus
  24. N. de Roux, E. Genin, J. Carel, F. Matsuda, J. Chaussain, and E. Milgrom, “Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 19, pp. 10972–10976, 2003. View at Publisher · View at Google Scholar · View at Scopus
  25. S. B. Seminara, S. Messager, E. E. Chatzidaki et al., “The GPR54 gene as a regulator of puberty,” The New England Journal of Medicine, vol. 349, no. 17, pp. 1614–1627, 2003. View at Publisher · View at Google Scholar · View at Scopus
  26. S. Funes, J. A. Hedrick, G. Vassileva et al., “The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system,” Biochemical and Biophysical Research Communications, vol. 312, no. 4, pp. 1357–1363, 2003. View at Publisher · View at Google Scholar · View at Scopus
  27. L. G. Silveira, A. C. Latronico, and S. B. Seminara, “Kisspeptin and clinical disorders.,” Advances in Experimental Medicine and Biology, vol. 784, pp. 187–199, 2013. View at Publisher · View at Google Scholar · View at Scopus
  28. M. G. Teles, E. B. Trarbach, S. D. Noel et al., “A novel homozygous splice acceptor site mutation of KISS1R in two siblings with normosmic isolated hypogonadotropic hypogonadism,” European Journal of Endocrinology, vol. 163, no. 1, pp. 29–34, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. A. K. Topaloglu, J. A. Tello, L. D. Kotan et al., “Inactivating KISS1 mutation and hypogonadotropic hypogonadism,” The New England Journal of Medicine, vol. 366, no. 7, pp. 629–635, 2012. View at Publisher · View at Google Scholar · View at Scopus
  30. J. R. Pedersen-White, L. P. Chorich, D. P. Bick, R. J. Sherins, and L. C. Layman, “The prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome,” Molecular Human Reproduction, vol. 14, no. 6, pp. 367–370, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. M. G. Teles, S. D. C. Bianco, V. N. Brito et al., “A GPR54-activating mutation in a patient with central precocious puberty,” The New England Journal of Medicine, vol. 358, no. 7, pp. 709–715, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. J. Roa, E. Vigo, J. M. Castellano et al., “Hypothalamic expression of KiSS-1 system and gonadotropin-releasing effects of kisspeptin in different reproductive states of the female rat,” Endocrinology, vol. 147, no. 6, pp. 2864–2878, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. J. T. Smith, “Sex steroid control of hypothalamic Kiss1 expression in sheep and rodents: comparative aspects,” Peptides, vol. 30, no. 1, pp. 94–102, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. A. K. Topaloglu, F. Reimann, M. Guclu et al., “TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction,” Nature Genetics, vol. 41, no. 3, pp. 354–358, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. P. Limonta and M. Manea, “Gonadotropin-releasing hormone receptors as molecular therapeutic targets in prostate cancer: current options and emerging strategies,” Cancer Treatment Reviews, vol. 39, no. 6, pp. 647–663, 2013. View at Publisher · View at Google Scholar · View at Scopus
  36. S. B. Seminara, M. J. DiPietro, S. Ramaswamy, W. F. Crowley Jr., and T. M. Plant, “Continuous human metastin 45–54 infusion desensitizes G protein-coupled receptor 54-induced gonadotropin-releasing hormone release monitored indirectly in the juvenile male Rhesus monkey (Macaca mulatta): a finding with therapeutic implications,” Endocrinology, vol. 147, no. 5, pp. 2122–2126, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. S. Ramaswamy, S. B. Seminara, C. R. Pohl, M. J. Dipietro, W. F. Crowley Jr., and T. M. Plant, “Effect of continuous intravenous administration of human metastin 45–54 on the neuroendocrine activity of the hypothalamic-pituitary-testicular axis in the adult male rhesus monkey (Macaca mulatta),” Endocrinology, vol. 148, no. 7, pp. 3364–3370, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. E. L. Thompson, V. Amber, G. W. H. Stamp et al., “Kisspeptin-54 at high doses acutely induces testicular degeneration in adult male rats via central mechanisms,” British Journal of Pharmacology, vol. 156, no. 4, pp. 609–625, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. E. L. Thompson, K. G. Murphy, M. Patterson et al., “Chronic subcutaneous administration of kisspeptin-54 causes testicular degeneration in adult male rats,” American Journal of Physiology-Endocrinology and Metabolism, vol. 291, no. 5, pp. E1074–E1082, 2006. View at Publisher · View at Google Scholar · View at Scopus
  40. V. M. Navarro, R. Fernández-Fernández, J. M. Castellano et al., “Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54,” The Journal of Physiology, vol. 561, no. 2, pp. 379–386, 2004. View at Publisher · View at Google Scholar · View at Scopus
  41. T. M. Plant, S. Ramaswamy, and M. J. DiPietro, “Repetitive activation of hypothalamic G protein-coupled receptor 54 with intravenous pulses of kisspeptin in the juvenile monkey (Macaca mulatta) elicits a sustained train of gonadotropin-releasing hormone discharges,” Endocrinology, vol. 147, no. 2, pp. 1007–1013, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. J. M. Castellano, V. M. Navarro, R. Fernández-Fernández et al., “Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition,” Endocrinology, vol. 146, no. 9, pp. 3917–3925, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. C. N. Jayasena, A. Abbara, J. D. Veldhuis et al., “Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of kisspeptin-54,” Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 6, pp. E953–E961, 2014. View at Google Scholar
  44. Y.-M. Chan, “Effects of kisspeptin on hormone secretion in humans,” Advances in Experimental Medicine and Biology, vol. 784, pp. 89–112, 2013. View at Publisher · View at Google Scholar · View at Scopus
  45. E. Hrabovszky and Z. Liposits, “Afferent neuronal control of type-I gonadotropin releasing hormone neurons in the human,” Frontiers in Endocrinology, vol. 4, article 130, 2013. View at Publisher · View at Google Scholar
  46. X. F. Li, J. S. Kinsey-Jones, Y. Cheng et al., “Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat,” PLoS ONE, vol. 4, no. 12, Article ID e8334, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. B. Francou, J. Bouligand, A. Voican et al., “Normosmic congenital hypogonadotropic hypogonadism due to TAC3/TACR3 mutations: characterization of neuroendocrine phenotypes and novel mutations,” PLoS ONE, vol. 6, no. 10, Article ID e25614, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. I. Sawyer, S. Smillie, J. V. Bodkin, E. Fernandes, K. T. O'Byrne, and S. D. Brain, “The vasoactive potential of kisspeptin-10 in the peripheral vasculature,” PLoS ONE, vol. 6, no. 2, Article ID e14671, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. T. Ramaesh, J. J. Logie, A. K. Roseweir et al., “Kisspeptin-10 inhibits angiogenesis in human placental vessels ex vivo and endothelial cells in vitro,” Endocrinology, vol. 151, no. 12, pp. 5927–5934, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. A. C. Hauge-Evans, C. C. Richardson, H. M. Milne, M. R. Christie, S. J. Persaud, and P. M. Jones, “A role for kisspeptin in islet function,” Diabetologia, vol. 49, no. 9, pp. 2131–2135, 2006. View at Publisher · View at Google Scholar · View at Scopus
  51. J. E. Bowe, A. J. King, J. S. Kinsey-Jones et al., “Kisspeptin stimulation of insulin secretion: mechanisms of action in mouse islets and rats,” Diabetologia, vol. 52, no. 5, pp. 855–862, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. R. A. Steiner, “Kisspeptin: past, present, and prologue,” Advances in Experimental Medicine and Biology, vol. 784, pp. 3–7, 2013. View at Publisher · View at Google Scholar · View at Scopus
  53. 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 Publisher · View at Google Scholar · View at Scopus
  54. G. Cheng, L. M. Coolen, V. Padmanabhan, R. L. Goodman, and M. N. Lehman, “The kisspeptin/neurokinin B/dynorphin (KNDy) cell population of the arcuate nucleus: sex differences and effects of prenatal testosterone in sheep,” Endocrinology, vol. 151, no. 1, pp. 301–311, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. M. N. Lehman, L. M. Coolen, and R. L. Goodman, “Minireview: kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone secretion,” Endocrinology, vol. 151, no. 8, pp. 3479–3489, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. J. Young, J. Bouligand, B. Francou et al., “TAC3 and TACR3 defects cause hypothalamic congenital hypogonadotropic hypogonadism in humans,” The Journal of Clinical Endocrinology & Metabolism, vol. 95, no. 5, pp. 2287–2295, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. E. Hrabovszky, M. T. Sipos, C. S. Molnár et al., “Low degree of overlap between kisspeptin, neurokinin B, and dynorphin immunoreactivities in the infundibular nucleus of young male human subjects challenges the KNDy neuron concept,” Endocrinology, vol. 153, no. 10, pp. 4978–4989, 2012. View at Publisher · View at Google Scholar · View at Scopus
  58. C. N. Jayasena, A. N. Comninos, A. de Silva et al., “Effects of neurokinin B administration on reproductive hormone secretion in healthy men and women,” Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 1, pp. E19–E27, 2014. View at Publisher · View at Google Scholar
  59. A. K. Roseweir, A. S. Kauffman, J. T. Smith et al., “Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation,” Journal of Neuroscience, vol. 29, no. 12, pp. 3920–3929, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. H. Matsui, Y. Takatsu, A. Tanaka et al., “251 potent and efficient testosterone suppression by chronic administration of novel metastin analogues, TAK-448 and TAK-683, in male rats,” European Journal of Cancer Supplements, vol. 8, article 66, 2010. View at Google Scholar
  61. G. Scott, I. Ahmad, K. Howard et al., “Double-blind, randomized, placebo-controlled study of safety, tolerability, pharmacokinetics and pharmacodynamics of TAK-683, an investigational metastin analogue in healthy men,” British Journal of Clinical Pharmacology, vol. 75, no. 2, pp. 381–391, 2013. View at Publisher · View at Google Scholar · View at Scopus