The Effects of Kisspeptin on Gonadotropin Release in Non-human Mammals

  • Ali Abbara
  • Risheka Ratnasabapathy
  • Channa N. Jayasena
  • Waljit S. Dhillo
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 784)

Abstract

The Kiss1 gene encodes a 145-amino acid pre-peptide, kisspeptin, which is cleaved into smaller peptides of 54, 14, 13, and 10 amino acids. This chapter reviews in detail the effects of kisspeptin on gonadotropin secretion in non-human mammals. Studies of kisspeptin’s effects have included both acute and chronic administration regimens via a number of administration routes. Acute kisspeptin stimulates gonadotropin secretion in a wide range of species of non-human mammals, including rats, mice, hamsters, sheep, pigs, goats, cows, horses, and monkeys. In general, the stimulatory effect of kisspeptin treatment is more pronounced for LH than FSH secretion. Kisspeptin is thought to exert its stimulatory effects on LH and FSH release via stimulation of GnRH release from the hypothalamus, since pre-­administration of a GnRH antagonist prevents kisspeptin’s stimulation of gonadotropin secretion. Although the kisspeptin receptor is also expressed on anterior pituitary cells of some species, and incubation of anterior pituitary cells with high concentrations of kisspeptin can stimulate in vitro LH release, the contribution of direct effects of kisspeptin on the pituitary is thought to be negligible in vivo. Continuous kisspeptin administration results in reduced sensitivity to the effects of kisspeptin, in some species. This desensitization is thought to occur at the level of the kisspeptin receptor, since the response of the pituitary gland to exogenous GnRH is maintained. Overall, the findings discussed in this chapter are invaluable to the understanding of the reproductive role of kisspeptin and the potential therapeutic uses of kisspeptin for the treatment of fertility disorders.

Keywords

Placebo Estrogen Testosterone Progesterone NMDA 

Notes

Acknowledgments

The section is funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7-HEALTH-2009-241592 EuroCHIP grant and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. A.A. is sponsored by a Wellcome Trust Clinical Training Fellowship, R.R. is sponsored by an NIHR Academic Training Fellowship, C.N.J. is supported by an NIHR Clinical Lectureship and Wellcome/AMS Starter Grant for Clinical Lecturers. W.S.D. is supported by an NIHR Career Development Fellowship.

References

  1. 1.
    Matsui H, Takatsu Y, Kumano S, Matsumoto H, Ohtaki T (2004) Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat. Biochem Biophys Res Commun 320(2):383–388PubMedCrossRefGoogle Scholar
  2. 2.
    Thompson EL, Amber V, Stamp GW, Patterson M, Curtis AE, Cooke JH, Appleby GF, Dhillo WS, Ghatei MA, Bloom SR, Murphy KG (2009) Kisspeptin-54 at high doses acutely induces testicular degeneration in adult male rats via central mechanisms. Br J Pharmacol 156(4):609–625PubMedCrossRefGoogle Scholar
  3. 3.
    Gottsch ML, Cunningham MJ, Smith JT, Popa SM, Acohido BV, Crowley WF, Seminara S, Clifton DK, Steiner RA (2004) A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 145(9):4073–4077PubMedCrossRefGoogle Scholar
  4. 4.
    Thompson EL, Patterson M, Murphy KG, Smith KL, Dhillo WS, Todd JF, Ghatei MA, Bloom SR (2004) Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-­pituitary-gonadal axis. J Neuroendocrinol 16(10):850–858PubMedCrossRefGoogle Scholar
  5. 5.
    Navarro VM, Castellano JM, Fernández-Fernández R, Tovar S, Roa J, Mayen A, Nogueiras R, Vazquez MJ, Barreiro ML, Magni P, Aguilar E, Dieguez C, Pinilla L, Tena-Sempere M (2005) Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54. Endocrinology 146(1):156–163PubMedCrossRefGoogle Scholar
  6. 6.
    Lents CA, Heidorn NL, Barb CR, Ford JJ (2008) Central and peripheral administration of ­kisspeptin activates gonadotropin but not somatotropin secretion in prepubertal gilts. Reproduction 135(6):879–887PubMedCrossRefGoogle Scholar
  7. 7.
    Jayasena CN, Nijher GM, Comninos AN, Abbara A, Januszewki A, Vaal ML, Sriskandarajah L, Murphy KG, Farzad Z, Ghatei MA, Bloom SR, Dhillo WS (2011) The effects of kisspeptin-­10 on reproductive hormone release show sexual dimorphism in humans. J Clin Endocrinol Metab 96(12):E1963–E1972PubMedCrossRefGoogle Scholar
  8. 8.
    Tovar S, Vázquez MJ, Navarro VM, Fernández-Fernández R, Castellano JM, Vigo E, Roa J, Casanueva FF, Aguilar E, Pinilla L, Dieguez C, Tena-Sempere M (2006) Effects of single or repeated intravenous administration of kisspeptin upon dynamic LH secretion in conscious male rats. Endocrinology 147(6):2696–2704PubMedCrossRefGoogle Scholar
  9. 9.
    Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM (2005) Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci U S A 102(6):2129–2134PubMedCrossRefGoogle Scholar
  10. 10.
    Hashizume T, Saito H, Sawada T, Yaegashi T, Ezzat AA, Sawai K, Yamashita T (2010) Characteristics of stimulation of gonadotropin secretion by kisspeptin-10 in female goats. Anim Reprod Sci 118(1):37–41PubMedCrossRefGoogle Scholar
  11. 11.
    Ohkura S, Takase K, Matsuyama S, Mogi K, Ichimaru T, Wakabayashi Y, Uenoyama Y, Mori Y, Steiner RA, Tsukamura H, Maeda KI, Okamura H (2009) Gonadotropin-releasing hormone pulse generator activity in the hypothalamus of the goat. J Neuroendocrinol 21(10):813–821PubMedCrossRefGoogle Scholar
  12. 12.
    Whitlock BK, Daniel JA, Wilborn RR, Rodning SP, Maxwell HS, Steele BP, Sartin JL (2008) Interaction of estrogen and progesterone on kisspeptin-10-stimulated luteinizing hormone and growth hormone in ovariectomized cows. Neuroendocrinology 88(3):212–215PubMedCrossRefGoogle Scholar
  13. 13.
    Magee C, Foradori CD, Bruemmer JE, Arreguin-Arevalo JA, McCue PM, Handa RJ, Squires EL, Clay CM (2009) Biological and anatomical evidence for kisspeptin regulation of the hypothalamic-­pituitary-gonadal axis of estrous horse mares. Endocrinology 150(6):2813–2821PubMedCrossRefGoogle Scholar
  14. 14.
    Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D, Dixon J, Thresher RR, Malinge I, Lomet D, Carlton MB, Colledge WH, Caraty A, Aparicio SA (2005) Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci U S A 102(5):1761–1766PubMedCrossRefGoogle Scholar
  15. 15.
    Mason AO, Greives TJ, Scotti MA, Levine J, Frommeyer S, Ketterson ED, Demas GE, Kriegsfeld LJ (2007) Suppression of kisspeptin expression and gonadotropic axis sensitivity following exposure to inhibitory day lengths in female Siberian hamsters. Horm Behav 52(4):492–498PubMedCrossRefGoogle Scholar
  16. 16.
    Plant TM, Ramaswamy S, Dipietro MJ (2006) 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 147(2):1007–1013PubMedCrossRefGoogle Scholar
  17. 17.
    Redmond JS, Macedo GG, Velez IC, Caraty A, Williams GL, Amstalden M (2011) Kisspeptin activates the hypothalamic-adenohypophyseal-gonadal axis in prepubertal ewe lambs. Reproduction 141(4):541–548PubMedCrossRefGoogle Scholar
  18. 18.
    Keen KL, Wegner FH, Bloom SR, Ghatei MA, Terasawa E (2008) An increase in kisspeptin-54 release occurs with the pubertal increase in LHRH-1 release in the stalk-median eminence of female rhesus monkeys in vivo. Endocrinology 149(8):4151–4157PubMedCrossRefGoogle Scholar
  19. 19.
    Castellano JM, Navarro VM, Fernández-Fernández R, Nogueiras R, Tovar S, Roa J, Vazquez MJ, Vigo E, Casanueva FF, Aguilar E, Pinilla L, Dieguez C, Tena-Sempere M (2005) Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology 146(9):3917–3925PubMedCrossRefGoogle Scholar
  20. 20.
    Belchetz PE, Plant TM, Nakai Y, Keogh EJ, Knobil E (1978) Hypophyseal responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone. Science 202(4368):631–633PubMedCrossRefGoogle Scholar
  21. 21.
    Seminara SB, Dipietro MJ, Ramaswamy S, Crowley WF Jr, Plant TM (2006) 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 147(5):2122–2126PubMedCrossRefGoogle Scholar
  22. 22.
    Ramzan F, Qureshi IZ (2011) Intraperitoneal kisspeptin-10 administration induces dose-­dependent degenerative changes in maturing rat testes. Life Sci 88(5–6):246–256PubMedCrossRefGoogle Scholar
  23. 23.
    Thompson EL, Murphy KG, Patterson M, Bewick GA, Stamp GW, Curtis AE, Cooke JH, Jethwa PH, Todd JF, Ghatei MA, Bloom SR (2006) Chronic subcutaneous administration of kisspeptin-54 causes testicular degeneration in adult male rats. Am J Physiol Endocrinol Metab 291(5):E1074–E1082PubMedCrossRefGoogle Scholar
  24. 24.
    Roa J, Vigo E, García-Galiano D, Castellano JM, Navarro VM, Pineda R, Diéguez C, Aguilar E, Pinilla L, Tena-Sempere M (2008) Desensitization of gonadotropin responses to kisspeptin in the female rat: analyses of LH and FSH secretion at different developmental and metabolic states. Am J Physiol Endocrinol Metab 294(6):E1088–E1096PubMedCrossRefGoogle Scholar
  25. 25.
    Caraty A, Smith JT, Lomet D, Ben Saïd S, Morrissey A, Cognie J, Doughton B, Baril G, Briant C, Clarke IJ (2007) Kisspeptin synchronizes preovulatory surges in cyclical ewes and causes ovulation in seasonally acyclic ewes. Endocrinology 148(11):5258–5267PubMedCrossRefGoogle Scholar
  26. 26.
    Revel FG, Saboureau M, Masson-Pévet M, Pévet P, Mikkelsen JD, Simonneaux V (2006) Kisspeptin mediates the photoperiodic control of reproduction in hamsters. Curr Biol 16(17):1730–1735PubMedCrossRefGoogle Scholar
  27. 27.
    Ansel L, Bentsen AH, Ancel C, Bolborea M, Klosen P, Mikkelsen JD, Simonneaux V (2011) Peripheral kisspeptin reverses short photoperiod-induced gonadal regression in Syrian hamsters by promoting GNRH release. Reproduction 142(3):417–425PubMedCrossRefGoogle Scholar
  28. 28.
    Jayasena CN, Nijher GM, Chaudhri OB, Murphy KG, Ranger A, Lim A, Patel D, Mehta A, Todd C, Ramachandran R, Salem V, Stamp GW, Donaldson M, Ghatei MA, Bloom SR, Dhillo WS (2009) Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis. J Clin Endocrinol Metab 94(11):4315–4323PubMedCrossRefGoogle Scholar
  29. 29.
    Smith JT, Li Q, Yap KS, Shahab M, Roseweir AK, Millar RP, Clarke IJ (2011) Kisspeptin is essential for the full preovulatory LH surge and stimulates GnRH release from the isolated ovine median eminence. Endocrinology 152(3):1001–1012PubMedCrossRefGoogle Scholar
  30. 30.
    Roseweir AK, Kauffman AS, Smith JT, Guerriero KA, Morgan K, Pielecka-Fortuna J, Pineda R, Gottsch ML, Tena-Sempere M, Moenter SM, Terasawa E, Clarke IJ, Steiner RA, Millar RP (2009) Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation. J Neurosci 29(12):3920–3929PubMedCrossRefGoogle Scholar
  31. 31.
    Irwig MS, Fraley GS, Smith JT, Acohido BV, Popa SM, Cunningham MJ, Gottsch ML, Clifton DK, Steiner RA (2004) Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat. Neuroendocrinology 80(4):264–272PubMedCrossRefGoogle Scholar
  32. 32.
    Han SK, Gottsch ML, Lee KJ, Popa SM, Smith JT, Jakawich SK, Clifton DK, Steiner RA, Herbison AE (2005) Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. J Neurosci 25(49):11349–11356PubMedCrossRefGoogle Scholar
  33. 33.
    Uenoyama Y, Inoue N, Pheng V, Homma T, Takase K, Yamada S, Ajiki K, Ichikawa M, Okamura H, Maeda KI, Tsukamura H (2011) Ultrastructural evidence of kisspeptin-­gonadotropin-releasing hormone (GnRH) interaction in the median eminence of female rats: implication of axo-axonal regulation of GnRH release. J Neuroendocrinol 23(10):863–870PubMedCrossRefGoogle Scholar
  34. 34.
    Herde MK, Geist K, Campbell RE, Herbison AE (2011) Gonadotropin-releasing hormone neurons extend complex highly branched dendritic trees outside the blood-brain barrier. Endocrinology 152(10):3832–3841PubMedCrossRefGoogle Scholar
  35. 35.
    Li XF, Kinsey-Jones JS, Cheng Y, Knox AM, Lin Y, Petrou NA, Roseweir A, Lightman SL, Milligan SR, Millar RP, O’Byrne KT (2009) Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat. PLoS One 4(12):e8334PubMedCrossRefGoogle Scholar
  36. 36.
    Ramaswamy S, Guerriero KA, Gibbs RB, Plant TM (2008) Structural interactions between kisspeptin and GnRH neurons in the mediobasal hypothalamus of the male rhesus monkey (Macaca mulatta) as revealed by double immunofluorescence and confocal microscopy. Endocrinology 149(9):4387–4395PubMedCrossRefGoogle Scholar
  37. 37.
    Smith JT, Shahab M, Pereira A, Pau KY, Clarke IJ (2010) Hypothalamic expression of KISS1 and gonadotropin inhibitory hormone genes during the menstrual cycle of a non-human ­primate. Biol Reprod 83(4):568–577PubMedCrossRefGoogle Scholar
  38. 38.
    Guerriero KA, Keen KL, Millar RP, Terasawa E (2012) Developmental changes in GnRH release in response to kisspeptin agonist and antagonist in female rhesus monkeys (Macaca mulatta): implication for the mechanism of puberty. Endocrinology 153(2):825–836PubMedCrossRefGoogle Scholar
  39. 39.
    Luque RM, Córdoba-Chacón J, Gahete MD, Navarro VM, Tena-Sempere M, Kineman RD, Castaño JP (2011) Kisspeptin regulates gonadotroph and somatotroph function in nonhuman primate pituitary via common and distinct signaling mechanisms. Endocrinology 152(3):957–966PubMedCrossRefGoogle Scholar
  40. 40.
    Gutiérrez-Pascual E, Martínez-Fuentes AJ, Pinilla L, Tena-Sempere M, Malagón MM, Castaño JP (2007) Direct pituitary effects of kisspeptin: activation of gonadotrophs and somatotrophs and stimulation of luteinising hormone and growth hormone secretion. J Neuroendocrinol 19(7):521–530PubMedCrossRefGoogle Scholar
  41. 41.
    Smith JT, Clay CM, Caraty A, Clarke IJ (2007) KiSS-1 messenger ribonucleic acid expression in the hypothalamus of the ewe is regulated by sex steroids and season. Endocrinology 148(3):1150–1157PubMedCrossRefGoogle Scholar
  42. 42.
    Suzuki S, Kadokawa H, Hashizume T (2008) Direct kisspeptin-10 stimulation on luteinizing hormone secretion from bovine and porcine anterior pituitary cells. Anim Reprod Sci 103(3–4):360–365PubMedCrossRefGoogle Scholar
  43. 43.
    Ezzat AA, Saito H, Sawada T, Yaegashi T, Goto Y, Nakajima Y, Jin J, Yamashita T, Sawai K, Hashizume T (2010) The role of sexual steroid hormones in the direct stimulation by kisspeptin-­10 of the secretion of luteinizing hormone, follicle-stimulating hormone and prolactin from bovine anterior pituitary cells. Anim Reprod Sci 121(3–4):267–272PubMedCrossRefGoogle Scholar
  44. 44.
    Oakley AE, Clifton DK, Steiner RA (2009) Kisspeptin signaling in the brain. Endocr Rev 30(6):713–743PubMedCrossRefGoogle Scholar
  45. 45.
    Dhillo WS, Chaudhri OB, Patterson M, Thompson EL, Murphy KG, Badman MK, McGowan BM, Amber V, Patel S, Ghatei MA, Bloom SR (2005) Kisspeptin-54 stimulates the hypothalamic-­pituitary gonadal axis in human males. J Clin Endocrinol Metab 90(12):6609–6615PubMedCrossRefGoogle Scholar
  46. 46.
    Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, Brézillon S, Tyldesley R, Suarez-Huerta N, Vandeput F, Blanpain C, Schiffmann SN, Vassart G, Parmentier M (2001) The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276(37):34631–34636PubMedCrossRefGoogle Scholar
  47. 47.
    Pheng V, Uenoyama Y, Homma T, Inamoto Y, Takase K, Yoshizawa-Kumagaye K, Isaka S, Watanabe TX, Ohkura S, Tomikawa J, Maeda K, Tsukamura H (2009) Potencies of centrally- or peripherally-injected full-length kisspeptin or its C-terminal decapeptide on LH release in intact male rats. J Reprod Dev 55(4):378–382PubMedCrossRefGoogle Scholar
  48. 48.
    Mikkelsen JD, Bentsen AH, Ansel L, Simonneaux V, Juul A (2009) Comparison of the effects of peripherally administered kisspeptins. Regul Pept 152(1–3):95–100PubMedCrossRefGoogle Scholar
  49. 49.
    Curtis AE, Cooke JH, Baxter JE, Parkinson JR, Bataveljic A, Ghatei MA, Bloom SR, Murphy KG (2010) A kisspeptin-10 analog with greater in vivo bioactivity than kisspeptin-10. Am J Physiol Endocrinol Metab 298(2):E296–E303PubMedCrossRefGoogle Scholar
  50. 50.
    Whitlock BK, Daniel JA, Wilborn RR, Maxwell HS, Steele BP, Sartin JL (2010) Interaction of kisspeptin and the somatotropic axis. Neuroendocrinology 92(3):178–188PubMedCrossRefGoogle Scholar
  51. 51.
    Ezzat Ahmed A, Saito H, Sawada T, Yaegashi T, Yamashita T, Hirata T, Sawai K, Hashizume T (2009) Characteristics of the stimulatory effect of kisspeptin-10 on the secretion of luteinizing hormone, follicle-stimulating hormone and growth hormone in prepubertal male and female cattle. J Reprod Dev 55(6):650–654PubMedCrossRefGoogle Scholar
  52. 52.
    Wahab F, Aziz F, Irfan S, Zaman WU, Shahab M (2008) Short-term fasting attenuates the response of the HPG axis to kisspeptin challenge in the adult male rhesus monkey (Macaca mulatta). Life Sci 83(19–20):633–637PubMedCrossRefGoogle Scholar
  53. 53.
    Wahab F, Ullah F, Chan YM, Seminara SB, Shahab M (2011) Decrease in hypothalamic Kiss1 and Kiss1r expression: a potential mechanism for fasting-induced suppression of the HPG axis in the adult male rhesus monkey (Macaca mulatta). Horm Metab Res 43(2):81–85PubMedCrossRefGoogle Scholar
  54. 54.
    Navarro VM, Fernández-Fernández R, Castellano JM, Roa J, Mayen A, Barreiro ML, Gaytan F, Aguilar E, Pinilla L, Dieguez C, Tena-Sempere M (2004) Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54. J Physiol 561(pt 2):379–386PubMedCrossRefGoogle Scholar
  55. 55.
    De Roux N, Genin E, Carel JC et al (2003) Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A 100:10972–10976PubMedCrossRefGoogle Scholar
  56. 56.
    Seminara SB, Messager S, Chatzidaki EE et al (2003) The GPR54 gene as a regulator of puberty. N Engl J Med 349:1614–1627PubMedCrossRefGoogle Scholar
  57. 57.
    Teles MG, Bianco SD, Brito VN, Trarbach EB, Kuohung W, Xu S, Seminara SB, Mendonca BB, Kaiser UB, Latronico AC (2008) A GPR54-activating mutation in a patient with central precocious puberty. N Engl J Med 358:709–715PubMedCrossRefGoogle Scholar
  58. 58.
    Pita J, Barrios V, Gavela-Pérez T, Martos-Moreno G, Muñoz-Calvo MT, Pozo J, Rovira A, Argente J, Soriano-Guillén L (2011) Circulating kisspeptin levels exhibit sexual dimorphism in adults, are increased in obese prepubertal girls and do not suffer modifications in girls with idiopathic central precocious puberty. Peptides 32(9):1781–1786PubMedGoogle Scholar
  59. 59.
    Terasawa E, Kurian JR, Keen KL, Shiel NA, Colman RJ, Capuano SV (2012) Body weight impact on puberty: effects of high-calorie diet on puberty onset in female rhesus monkeys. Endocrinology 153(4):1696–1705PubMedCrossRefGoogle Scholar
  60. 60.
    Castellano JM, Navarro VM, Fernández-Fernández R, Castaño JP, Malagón MM, Aguilar E, Dieguez C, Magni P, Pinilla L, Tena-Sempere M (2006) Ontogeny and mechanisms of action for the stimulatory effect of kisspeptin on gonadotropin-releasing hormone system of the rat. Mol Cell Endocrinol 257–258:75–83PubMedCrossRefGoogle Scholar
  61. 61.
    Greives TJ, Long KL, Burns CM, Demas GE (2011) Response to exogenous kisspeptin varies according to sex and reproductive condition in Siberian hamsters (Phodopus sungorus). Gen Comp Endocrinol 170(1):172–179PubMedCrossRefGoogle Scholar
  62. 62.
    Roa J, Vigo E, Castellano JM, Navarro VM, Fernández-Fernández R, Casanueva FF, Dieguez C, Aguilar E, Pinilla L, Tena-Sempere M (2006) Hypothalamic expression of KiSS-1 system and gonadotropin-releasing effects of kisspeptin in different reproductive states of the female Rat. Endocrinology 147(6):2864–2878PubMedCrossRefGoogle Scholar
  63. 63.
    Knobil E (1980) The neuroendocrine control of the menstrual cycle. Recent Prog Horm Res 36:53–88PubMedGoogle Scholar
  64. 64.
    Smith JT, Dungan HM, Stoll EA, Gottsch ML, Braun RE, Eacker SM, Clifton DK, Steiner RA (2005) Differential regulation of KiSS-1 mRNA expression by sex steroids in the brain of the male mouse. Endocrinology 146(7):2976–2984PubMedCrossRefGoogle Scholar
  65. 65.
    d’Anglemont de Tassigny X, Fagg LA, Carlton MB, Colledge WH (2008) Kisspeptin can stimulate gonadotropin-releasing hormone (GnRH) release by a direct action at GnRH nerve terminals. Endocrinology 149(8):3926–3932PubMedCrossRefGoogle Scholar
  66. 66.
    Zhang C, Bosch MA, Ronnekleiv OK, Kelly MJ (2009) Gamma-aminobutyric acid B receptor mediated inhibition of gonadotropin-releasing hormone neurons is suppressed by kisspeptin-G protein-coupled receptor 54 signaling. Endocrinology 150:2388–2394PubMedCrossRefGoogle Scholar
  67. 67.
    Sébert ME, Lomet D, Saïd SB, Monget P, Briant C, Scaramuzzi RJ, Caraty A (2010) Insights into the mechanism by which kisspeptin stimulates a preovulatory LH surge and ovulation in seasonally acyclic ewes: potential role of estradiol. Domest Anim Endocrinol 38(4):289–298Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  • Ali Abbara
    • 1
  • Risheka Ratnasabapathy
    • 1
  • Channa N. Jayasena
    • 1
  • Waljit S. Dhillo
    • 1
  1. 1.Division of Diabetes, Endocrinology and Metabolism, Department of Investigative MedicineImperial College LondonLondonUK

Personalised recommendations