J Appl Biomed 8:1-9, 2010 | DOI: 10.2478/v10136-009-0001-0

The kiss-1-kisspeptin-gpr54 complex: a critical modulator of GnRH neurons during pubertal activation

César Alberto Meza-Herrera1,*, Francisco Gerardo Veliz-Deras2, Maria Wurzinger3, Bernardo López-Ariza1, Gerardo Arellano-Rodriguez2, Rafael Rodriguez-Martinez2
1 Universidad Autónoma Chapingo, Unidad Regional Universitaria de Zonas Áridas, Bermejillo, Durango, Mexico
2 Universidad Autónoma Agraria Antonio Narro, Unidad Laguna, Mexico
3 BOKU - University of Natural Resources and Applied Life Sciences, Austria

Establishment of the hypothalamic-hypophyseal-gonadal function is dependent on the highly controlled and dynamic interactions between regulatory signals from the brain, pituitary and gonads, all of them leading to the attainment of reproductive capacity, where a coordinated and timely activation of GnRH neurons must occur. The GnRH neurons extend their neurosecretory axons to the hypothalamus where GnRH is released into the pituitary portal vessels to elicit the secretion of LH and FSH, which in turn, will promote gonadal development and support reproductive physiology. Genetic studies have demonstrated that disabling mutations and targeted deletions of the G-protein-coupled receptor (GPR54) generated hypogonadotropic hypogonadism. This link between GPR54 and reproduction, generated attention to the natural ligands of the GPR54 receptor, known as kisspeptins, which are translational products of the hypothalamic gene KiSS1. Recent advances in kisspeptin research have defined a major role of this molecule in controlling the onset of the reproductive function observed at puberty. The aim of this review is to highlight the basic endocrine and genetic concepts involved in the establishment of the hypothalamic-hypophyseal-gonadal axis function which promotes the onset of the reproductive function during puberty. The review highlights what is currently known about the kisspeptin-GPR54 signalling system in the activation of the GnRH neurons.

Keywords: reproductive axis; GnRH neurons; kisspeptin-GPR54 system; puberty

Received: August 10, 2009; Published: March 31, 2010  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Meza-Herrera CA, Gerardo Veliz-Deras F, Wurzinger M, López-Ariza B, Arellano-Rodriguez G, Rodriguez-Martinez R. The kiss-1-kisspeptin-gpr54 complex: a critical modulator of GnRH neurons during pubertal activation. J Appl Biomed. 2010;8(1):1-9. doi: 10.2478/v10136-009-0001-0.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Aparicio SA: Kisspeptins and GPR54: The new biology of the mammalian GnRH axis. Cell Metab 1:293-296, 2005. Go to original source... Go to PubMed...
    2. Apter D: Development of the hypothalamic-pituitary-ovarian axis. Ann NY Acad Sci 816:9-21, 1997. Go to original source... Go to PubMed...
    3. Apter D, Hermanson E: Update on female pubertal development. Curr Opin Obstet Gynecol 14:475-481, 2003. Go to original source... Go to PubMed...
    4. Arechiga-Flores CF, Bañuelos-Valenzuela R, Rincon-Delgado RM, Meza-Herrera CA: Attainment of puberty in winter-born hair-ewe lambs under natural photoperiod (22 NL): Preliminary results. Wool Technol Sheep Breed 52:35-42, 2004.
    5. Belsham DD, Lovejoy DA: Gonadotropin-releasing hormone: Gene evolution, expression and regulation. Vitam Horm 71:59-94, 2005. Go to original source... Go to PubMed...
    6. Boukhliq R, Goodman RL, Berriman SJ, Adrian B, Lehman MN: A subset of gonadotropin-releasing hormone neurons in the ovine medial basal hypothalamus is activated during increased pulsatile luteinizing hormone secretion. Endocrinology 140:5929-5236, 1999. Go to original source... Go to PubMed...
    7. Brown RE, Imran SA, Ur E, Wilkinson M: KiSS-1 mRNA in adipose tissue is regulated by sex hormones and food intake. Mol Cell Endocrinol 281:64-72, 2008. Go to original source... Go to PubMed...
    8. Bronson FH: Puberty in female mice is not associated with increases in either body fat or leptin. Endocrinology 142:4758-4761, 2001. Go to original source... Go to PubMed...
    9. Carrillo M, Zanuy S, Felip A, Bayarri MJ, Moles G, Gomez A: Hormonal and environmental control of puberty in perciform fish: the case of sea bass. Ann NY Acad Sci 1163:49-59, 2009. Go to original source... Go to PubMed...
    10. Castellano JM, Navarro VM, Fernandez-Fernandez R, Noguerias R, Tovar S, Roa J, Tena-Sempere M: Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology 146:3917-3925, 2005. Go to original source... Go to PubMed...
    11. Castellano JM, Gaytan M, Roa J, Vigo E, Navarro VM, Bellido C, Dueguez C, Aguilar E, Sanchez-Criado JE, Pellicer A, Pinilla L, Gaytan F et al.: Expression of KiSS-1 in rat ovary: putative local regulator of ovulation? Endocrinology 147:4852-4862, 2006a. Go to original source... Go to PubMed...
    12. Castellano JM, Navarro VM, Fernandez-Fernandez R, Castaño JP, Malagon MM, Aguilar E, Dieguez C, Magni P, Pinilla L, Tena-Sempere M: Ontogeny and mechanisms of action for the stimulatory effect of kisspeptin on gonadotropin-releasing hormon system in the rat. Mol Cel Endocrinol 257-258:75-83, 2006b. Go to original source... Go to PubMed...
    13. Cheung CC, Thornton JE, Kuijper JL, Weigle DS, Clifton DK, Steiner RA: Leptin is a metabolic gate for the onset of puberty in the female rat. Endocrinology 138:855-857, 1997. Go to original source... Go to PubMed...
    14. Clark IJ, Smith JT, Caraty A, Goodman RL, Lehman MN: Kisspeptin and seasonality in sheep. Peptides 30:154-163, 2009. Go to original source... Go to PubMed...
    15. Clarke IJ, Pompolo S: Synthesis and secretion of GnRH. Anim Reprod Sci 88:29-55, 2005. Go to original source... Go to PubMed...
    16. Clarkson J, Herbison AE: Development of GABA and glutamate signaling at the GnRH neuron in relation to puberty. Moll Cell Endocrinol 25:32-38, 2006. Go to original source... Go to PubMed...
    17. DiVall SA, Radovick S: Endocrinology of female puberty. Curr Opin Endocrinol Diabetes Obes 16:1-4, 2009. Go to original source... Go to PubMed...
    18. Ebling FJ: The neuroendocrine timing of puberty. Reproduction 129:675-683, 2005. Go to original source... Go to PubMed...
    19. Gamez-Vazquez HG, Rosales-Nieto CA, Bañuelos-Valenzuela R, Urrutia-Morales J, Diaz-Gomez MO, Silva-Ramos JM, Meza-Herrera CA: Body condition score positively influence plasma leptin concentrations in criollo goats. J Anim Vet Adv 7:1237-1240, 2008.
    20. Garcia-Segura LM, McCarthy MM: Minireview: role of glia in neuroendocrine function. Endocrinology 145:1082-1086, 2004. Go to original source... Go to PubMed...
    21. Gill JC, Moenter SM, Tsai PS: Developmental regulation of gonadotropin-releasing hormone neurons by fibroblast growth factor signalling. Endocrinology 145:3830-3839, 2004. Go to original source... Go to PubMed...
    22. Goldman BD: Mammalian photoperiodic system: Formal properties and neuroendocrine mechanisms of photoperiodic time measurement. J Biol Rhythms 16:283-301, 2001. Go to original source... Go to PubMed...
    23. Gottsch ML, Clifton DK, Steiner RA: Kisspeptin-GPR54 signaling in the neuroendocrine reproductive axis. Mol Cell Endocrinol 25:91-96, 2006. Go to original source... Go to PubMed...
    24. Guerra-García M, Meza-Herrera CA, Sanchez-Torres-Esqueda MT, Gallegos-Sanchez J, Torres-Hernandez G, Pro-Martinez A: IGF-1 and ovarian activity of goats in divergent body condition and supplemented with non-degradable ruminal protein. Agrociencia 4:241-247, 2009.
    25. Gutierrez-Pascual E, Martinez-Fuentes AJ, Pinilla L, Tena-Sempere M, Malagon MM, Castano JP: Direct pituitary effects of kisspeptin: activation of gonadotrophs and somatothrops and stimulation of luteinizing hormone and growth hormone secretion. J Neuroendocrinol 19:521-530, 2007. Go to original source... Go to PubMed...
    26. Heger S, Mastronardi C, Dissen GA, Lomniczi A, Cabrera R, Roth CL, Jung H, Calimi F, Sippell W, Ojeda SR: Enhanced at puberty 1 (EAP1) is a new transcriptional regulator of the female neuroendocrine axis. J Clin Invest 117:2145-2154, 2007. Go to original source... Go to PubMed...
    27. Hughes IA, Kumanan M: A wider perspective on puberty. Moll Cell Endocrinol 25:1-7, 2006. Go to original source... Go to PubMed...
    28. Jimenez-Linan M, Rubin BS, King JC: Examination of guinea pig luteinizing hormone-releasing hormone gene reveals a unique decapeptide and existence of two transcripts in the brain. Endocrinology 138:4123-4130, 1997. Go to original source... Go to PubMed...
    29. Kadokawa H, Suzuki S, Hashizume T: Kisspeptin-10 stimulates the secretion of growth hormone and prolactin directly from cultures bovine anterior pituitary cells. Anim Reprod Sci 105:404-408, 2008. Go to original source... Go to PubMed...
    30. Kotani M, Detheux M, Vandebogaerde A, Communi D, Vanderwinden JM, Blanpain C, Schiftfmann SN, Vassart G, Parmentier M: The metastasis suppressor gene KiSS1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276:34631-34636, 2001. Go to original source... Go to PubMed...
    31. Latimer VS, Rodrigues SM, Grayfallou VT, Kphama SG, White RB, Frenald RD, Urbanski HF: Two molecular forms of gonadotropin-releasing hormone (GnRH-I and GnRH-II) are expressed by two separate populations of cells in the rhesus macaque hypothalamus. Brain Res Mol Brain Res 75:287-292, 2000. Go to original source... Go to PubMed...
    32. Lehman MN, Robinson JE, Karsch FJ, Silverman AJ: Immunocytochemical localization of luteinizing hormone-releasing hormone (LHRH) pathways in the sheep brain during anestrus and the mid-luteal phase of the estrous cycle. J Comp Neurol 244:19-35, 1986. Go to original source... Go to PubMed...
    33. Lee DK, Nguyen T, O'Neill GP, Cheng R, Liu Y, Howard AD, Coulombe N, Tan CP, Tang-Nguyen AT, George SR, O'Dowd BF: Discovery of a receptor related to galanin receptors. FEBS Lett 446:103-107, 1999. Go to original source... Go to PubMed...
    34. Maffucci JA, Gore AC: Hypothalamic neural systems controlling the female reproductive life cycle: Gonadotropin-releasing hormone, glutamate and GABA. In Kwang WJ (ed.): International Review of Cell and Molecular Biology, Vol. 274, Academic Press, Burlington 2009, pp. 69-127. Go to original source...
    35. Malpaux B, Migaud M, Tricoire H, Chemineau P: Biology of mammalian photoperioidism and the critical role of the pineal gland and melatonin. J Biol Rhythms 16:336-347, 2001. Go to original source... Go to PubMed...
    36. Marshall PE, Goldsmith PC: Neuroregulatory and neuroendocrine GnRH pathways in the hypothalamus and forebrain of the baboon. Brain Res 193:357-372, 1980. Go to original source... Go to PubMed...
    37. Messinis IE: From menarche to regular menstruation: Endocrinological background. Ann NY Acad Sci 1042:49-56, 2006. Go to original source... Go to PubMed...
    38. Meza-Herrera CA, Sanchez JM, Chavez-Perches JG, Salinas H, Mellado M: Protein supplementation, body condition and ovarian activity in goats. Preovulatory serum profile of insulin. S Afr J Anim Sci 34:223-226, 2004.
    39. Meza-Herrera CA, Ross T, Hallford DM, Hawkins D, Gonzalez-Bulnes A: Effects of body condition and protein supplementation on LH secretion and luteal function in sheep. Reprod Domest Anim 42:461-465, 2007. Go to original source... Go to PubMed...
    40. Meza-Herrera CA, Hallford DM, Ortiz JA, Cuevas RA, Sanchez JM, Salinas H, Mellado M, Gonzalez-Bulnes A: Body condition and protein supplementation positively affect periovulatory ovarian activity by non-LH mediated pathways in goats. Anim Reprod Sci 106:412-420, 2008. Go to original source... Go to PubMed...
    41. Meza-Herrera CA, Gonzalez-Bulnes A, Kridli R, Mellado M, Arechiga-Flores CF, Salinas H, Luginbhul JM: Neuroendocrine, metabolic and genomic cues signaling the onset of puberty in females. Reprod Domest Anim 2009. doi: 10.1111/j.1439-0531.2009.01355.x Go to original source...
    42. Mikkelsen JD, Simonneaux V: The neuronantomy of the kisspeptin system in the mammalian brain. Peptides 30:26-33, 2009. Go to original source... Go to PubMed...
    43. Muir AI, Chamberlain L, Elshourbagy A, Michalovich D, Moore DJ, Calamari A, Szekeres PG, Sarau HM, Chambers JK, Murdock P, Steplewski K, Shabon U et al.: AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS1. J Biol Chem 276:28969-28975, 2001. Go to original source... Go to PubMed...
    44. Muñoz-Gutierrez M, Findlay PA, Adam CL, Wax G, Campbell BK, Kendall NR, Khalid M, Forsberg M, Scaramuzzi RJ: The ovarian expression of mRNAs for aromatase, IGF-I receptor, IGF-binding protein-2, 4 and 5, leptin receptor in cycling ewes after three days of leptin infusion. Reproduction 130:869-881, 2005. Go to original source... Go to PubMed...
    45. Ojeda SR, Roth C, Mungenast A, Heger S, Mastronardi C, Parent AS, Lomniczi A, Jung H: Neuroendocrine mechanisms controlling female puberty: new approaches, new concepts. Int J Androl 29:286-290, 2006a. Go to original source... Go to PubMed...
    46. Ojeda SR, Lomniczi A, Mastronardi C, Heger S, Roth C, Parent AS Matagne V, Mungenast AE: The neuroendocrine regulation of puberty: Is time ripe for a systems biology approach? Endocrinology 147:1166-1174, 2006b. Go to original source... Go to PubMed...
    47. Popa SM, Clifton DK, Steiner RA: A KiSS to remember. Trends Endocrinol Metab 16:249-250, 2005. Go to original source... Go to PubMed...
    48. Prevot V, Dehouck B, Poulain P, Beauvillain JC, Buee-Scherrer V, Bouret S: Neuronal-glial-endotelial interactions and cell plasticity in the postnatal hypothalamus: Implications for the neuroendocrine control of reproduction. Psychoneuroendocrinology 32:546-551, 2007. Go to original source... Go to PubMed...
    49. Ramakrishnappa N, Rajamadhendran N, Yung-Ming, L, Leung PCK: GnRH in non-hypothalamic reproductive tissues. Anim Reprod Sci 88:95-113, 2005. Go to original source... Go to PubMed...
    50. Revel FT, Saboureau, M, Masson-Pevet M, Pevet P, Mikkelsen JD, Simonneaux V: Kisspeptin mediates the photoperiodic control of reproduction in hamsters. Curr Biol 16:1730-1735, 2006. Go to original source... Go to PubMed...
    51. Roa J, Tena-Sempere M: KiSS-1 system and reproduction: comparative aspects and roles in the control of female gonadotropic axis in mammals. Gen Comp Endocrinol 153:132-140, 2007. Go to original source... Go to PubMed...
    52. Roseweir AK, Millar RP: The role of kisspeptin in the control of gonadotrophin secretion. Hum Reprod Update 15:203-212, 2009. Go to original source... Go to PubMed...
    53. Roth C, Schricker M, Lakomek M, Strege A, Heiden I, Luft H, Munzel U, Wuttke W, Jarry H: Autoregulation of the gonadotropin-releasing hormone (GnRH) system during puberty: effects of antagonistic versus agonistic GnRH analogs in a female rat model. J Endocrinol 169:361-371, 2001. Go to original source... Go to PubMed...
    54. Scaramuzzi RJ, Campbell BK, Downing JA, Kendall NR, Khalid M, Muñoz-Gutierrez M, Somchit A: A review of the effects of suplementary nutrition in the ewe on the concentrations of reproductcive and metabolic hormones and the mechanisms that regulate folliculogenesis and ovulation rate. Reprod Nutr Dev 46:339-354, 2006. Go to original source... Go to PubMed...
    55. Sills ES, Walsh AP: The GPR54-Kisspeptin complex in reproductive biology: neuroendocrine significance and implications for ovulation induction and contraception. Neuro Endocrinol Lett 29:846-851, 2008. Go to PubMed...
    56. Simonneaux V, Ribelayga C: Generation of the melatonin endocrine message in mammals: A review of the complex regulation of melatonin synthesis by norepinephrine, peptides and other pineal transmitters. Pharmacol Rev 55:325-395, 2003. Go to original source... Go to PubMed...
    57. Singh R, Graves ML, Roskelly CD, Giritharan G, Rajamahendran M: Gonadotropin releasing hormone receptor gene and protein expression and immunohistochemical localization in bovine uterus and oviducts. Domest Anim Endocrinol 34:319-326, 2008. Go to original source... Go to PubMed...
    58. Smith JT, Dungan HM, Stoll EA, Gottsch ML, Braun RE, Eacker SM, Clifton DK, Steiner RA: Differential regulation of KiSS1 mRNA by sex steroids in the brain of the male mouse. Endocrinology 146:2976-2984, 2005. Go to original source... Go to PubMed...
    59. Suttie JM, Kostyo JL, Ebling FJ, Wood RI, Bucholtz DC, Skottner A, Adel TE, Towns RJ, Foster DL: Metabolic interphases between growth and reproduction. IV. Chronic pulsatile administration of growth hormone and the timing of puberty in sheep. Endocrinology 129:2024-2032, 1998. Go to original source... Go to PubMed...
    60. Suzuki S, Kadokawa H, Hashizume T: Direct kisspeptin-10 stimulation on luteinizing hormone secretion from bovine and porcine anterior pituitary cells. Anim Reprod Sci 3:360-365, 2008. Go to original source... Go to PubMed...
    61. Tena-Sempere M: The roles of kisspeptins and G-protein-coupled receptor 54 in pubertal development. Curr Opin Pediatr 18:442-447, 2006a. Go to original source... Go to PubMed...
    62. Tena-Sempere M: KISS-1 and reproduction: Focus on its role in the metabolic regulation of fertility. Neuroendocrinology 83:275-281, 2006b. Go to original source... Go to PubMed...
    63. Tena-Sempere M: GPR54 and kisspeptin in reproduction. Hum Reprod Update 12:631-639, 2006c. Go to original source... Go to PubMed...
    64. Teresawa E: Role of GABA in the mechanism of the onset of puberty in non-human primates. Int Rev Neurobiol 71:113-129, 2005. Go to original source... Go to PubMed...
    65. Terasawa E, Fernandez DL: Neurobiological mechanisms of the onset of puberty in primates. Endocr Rev 22:111-151, 2001. Go to original source...
    66. Veliz FG, Meza-Herrera CA, de Santiago-Miramontes MA, Arellano-Rodriguez G, Leyva C, Rivas-Muñoz R, Mellado M: Effect of parity and progesterone priming on induction of reproductive function in Saanen goats by buck exposure. Livest Sci 125:261-265, 2009. Go to original source...
    67. Whitlock KE, Illing N, Brideau NJ, Smith KM, Twomey S: Development of GnRH cells: Setting the stage for puberty. Moll Cell Endocrinol 25:39-50, 2006. Go to original source... Go to PubMed...
    68. Wray S: Development of luteinizing hormone releasing neurons. J Neuroendocrinol 13:2-11, 2001. Go to original source... Go to PubMed...
    69. Zapatero-Caballero H, Sanchez-Franco F, Fernandez-Mendez C, Garcia-Sanrutos M, Botella-Cubells LM, Fernandez-Vazquez G: Gonadotropin-releasing hormona expresión during pubertal development in rats. Biol Reprod 70:348-355, 2004. Go to original source... Go to PubMed...

    Return to the content