ISSN 1214-0287 (on-line), ISSN 1214-021X (printed)|
J Appl Biomed
Volume 8 (2010), No 1, p 1-9
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.
reproductive axis; GnRH neurons; kisspeptin-GPR54 system; puberty
Aparicio SA: Kisspeptins and GPR54: The new biology of the mammalian GnRH axis. Cell Metab 1:293-296, 2005.
Apter D: Development of the hypothalamic-pituitary-ovarian axis. Ann NY Acad Sci 816:9-21, 1997.
Apter D, Hermanson E: Update on female pubertal development. Curr Opin Obstet Gynecol 14:475-481, 2003.
Arechiga-Flores CF, Banuelos-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 Technology and Sheep Breeding 52:35-42, 2004.
Belsham DD, Lovejoy DA: Gonadotropin-releasing hormone: Gene evolution, expression and regulation. Vitam Horm 71:59-94, 2005.
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.
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.
Bronson FH: Puberty in female mice is not associated with increases in either body fat or leptin. Endocrinology 142:4758-4761, 2001.
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.
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.
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, Tena-Sempere M: Expression of KiSS-1 in rat ovary: putative local regulator of ovulation? Endocrinology 147:4852-4862, 2006a.
Castellano JM, Navarro VM, Fernandez-Fernandez R, Castano 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.
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.
Clark IJ, Smith JT, Caraty A, Goodman RL, Lehman MN: Kisspeptin and seasonality in sheep. Peptides 30:154-163, 2009.
Clarke IJ, Pompolo S: Synthesis and secretion of GnRH. Anim Reprod.Sci 88:29-55, 2005.
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.
DiVall SA, Radovick S: Endocrinology of female puberty. Curr Opin Endocrinol Diabetes Obes 16:1-4, 2009.
Ebling FJ: The neuroendocrine timing of puberty. Reproduction 129:675-683, 2005.
Gamez-Vazquez HG, Rosales-Nieto CA, Banuelos-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.
Garcia-Segura LM, McCarthy MM: Minireview: role of glia in neuroendocrine function. Endocrinology 145:1082-1086, 2004.
Gill JC, Moenter SM, Tsai PS: Developmental regulation of gonadotropin-releasing hormone neurons by fibroblast growth factor signalling. Endocrinology 145:3830–3839, 2004.
Goldman BD: Mammalian photoperiodic system: Formal properties and neuroendocrine mechanisms of photoperiodic time measurement. J Biol Rhythms 16:283-301, 2001.
Gottsch ML, Clifton DK, Steiner RA: Kisspeptin-GPR54 signaling in the neuroendocrine reproductive axis. Mol Cell Endocrinol 25:91-96, 2006.
Guerra-Garcia 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 43:241-247, 2009.
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 Neuroendocrinology 19:521-530, 2007.
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.
Hughes IA, Kumanan M: A wider perspective on puberty. Moll Cell Endocrinol 25:1-7, 2006.
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.
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.
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.
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.
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.
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.
Maffucci JA, Gore AC: Hypothalamic neural systems controlling the female reproductive life cycle: Gonadotropin-releasing hormone, glutamate and GABA. In: Kwang W (ed.): International Review of Cell and Molecular Biology. Vol. 274, Burlington, Academic Press. pp. 69-127, 2009.
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.
Marshall PE, Goldsmith PC: Neuroregulatory and neuroendocrine GnRH pathways in the hypothalamus and forebrain of the baboon. Brain Res 193:357-372, 1980.
Messinis IE: From menarche to regular menstruation: Endocrinological background. Ann NY Acad Sci 1042:49-56, 2006.
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. South Afric J Animal Sci 34:223-226, 2004.
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.
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.
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
Mikkelsen JD, Simonneaux V: The neuronantomy of the kisspeptin system in the mammalian brain. Peptides 30:26-33, 2009.
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.
Munoz-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.
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.
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.
Popa SM, Clifton DK, Steiner RA: A KiSS to remember. Trends Endocrinol Metab 16:249–250, 2005.
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.
Ramakrishnappa N, Rajamadhendran N, Yung-Ming, L, Leung PCK: GnRH in non-hypothalamic reproductive tissues. Anim Reprod Sci 88:95-113, 2005.
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.
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.
Roseweir AK, Millar RP: The role of kisspeptin in the control of gonadotrophin secretion. Hum Reprod Update 15:203-212, 2009.
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.
Scaramuzzi RJ, Campbell BK, Downing JA, Kendall NR, Khalid M, Munoz-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.
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.
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.
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.
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.
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.
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.
Tena-Sempere M: The roles of kisspeptins and G-protein-coupled receptor 54 in pubertal development. Curr Opin Pediatr 18:442-447, 2006a.
Tena-Sempere M: KISS-1 and reproduction: Focus on its role in the metabolic regulation of fertility. Neuroendocrinology 83:275-281, 2006b.
Tena-Sempere M: GPR54 and kisspeptin in reproduction. Hum Reprod Update 12:631-639, 2006c.
Teresawa E: Role of GABA in the mechanism of the onset of puberty in non-human primates. Int Rev Neurobiol 71:113-129, 2005.
Terasawa E, Fernandez DL: Neurobiological mechanisms of the onset of puberty in primates. Endocr Rev 22:111-151, 2001.
Veliz FG, Meza-Herrera CA, de Santiago-Miramontes MA, Arellano-Rodriguez G, Leyva C, Rivas-Munoz R, Mellado M: Effect of parity and progesterone priming on induction of reproductive function in Saanen goats by buck exposure. Livest Sci 125:261265, 2009.
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.
Wray S: Development of luteinizing hormona releasing neurons. J Neuroendocrinol 13:2-11, 2001.
Zapatero-Caballero H, Sanchez-Franco F, Fernandez-Mendez C, Garcia-Sanrutos M, Botella-Cubells LM, Fernandez-Vazquez G: Gonadotropin-releasing hormone expresion during pubertal development in rats. Biol Reprod 70:348-355, 2004.
Meza-Herrera CA, Vargas-Beltran F, Vergara-Hernandez HP, Macias-Cruz U, Avendano-Reyes L, Rodriguez-Martinez R, Arellano-Rodriguez G, Veliz-Deras FG. Betacarotene supplementation increases ovulation rate without an increment in LH secretion in cyclic goats. Reprod Biol. 13: 51-57, 2013.
Urrutia-Morales J, Meza-Herrera CA Tello-Varela L, Diaz-Gomez MO, Beltran-Lopez S. Effect of nutritional supplementation upon pregnancy rates of goats under semiarid rangelands and exposed to the male effect. Tropic Anim Health Prod. 44: 1473-1477, 2012.
Meza-Herrera CA, Hernandez-Valenzuela LC, Gonzalez-Bulnes A, Tena-Sempere M, Abad-Zavaleta J, Salinas-Gonzalez H, Mellado M, Veliz-Deras F. Long-term betacarotene-supplementation enhances serum insulin concentrations without effect on the onset of puberty in the female goat. Reproduc Biol. 11: 236-249, 2011.
Arroyo J. Reproductive seasonality of sheep in Mexico [Estacionalidad reproductiva de la oveja en México]. Tropic Subtropic Agroecosys. 14: 829-845, 2011.
Sawalha MN Kridli RT Jawasreh KI Meza-Herrera CA. The use of melatonin and progestagen-eCG to initiate reproductive activity in prepuberal Awassi ewe lambs. Trop Anim Health Prod. 43: 1345-1350, 2011.
Berger J. The age of biomedicine: current trends in traditional subjects. J Appl Biomed. 9: 57-61, 2011.
Meza-Herrera CA, Torres-Moreno M, Lopez-Medrano JI, Gonzalez-Bulnes A, Veliz FG, Mellado M, Wurzinger M, Soto-Sanchez MJ, Calderon-Leyva MG. Glutamate supply positively affects serum release of triiodothyronine and insulin across time without increases of glucose during the onset of puberty in female goats. Anim Reprod Sci. 125: 74-80, 2011.
Rosales-Nieto CA, Gamez-Vazquez HG, Gudino-Reyes J, Reyes-Ramirez EA, Eaton M, Stanko RL, Meza-Herrera CA, Gonzalez-Bulnes A. Nutritional and metabolic modulation of the male effect on the resumption of ovulatory activity in goats. Anim Prod Sci. 51: 115-122, 2011.
Flores-Najera MJ, Meza-Herrera CA, Echavarria FG, Villagomez E, Iniguez L, Salinas H, Gonzalez-Bulnes A. Influence of nutritional and socio-sexual cues upon reproductive efficiency of goats exposed to the male effect under extensive conditions. Anim Product Sci. 50: 897-901, 2010.