Kisspeptin (kiss 1) network signaling of hypothalamic gonadotropin-releasing hormone (GnRH) neurons

• Autorzy: Przekop E. , Ciechanowska M.
• Języki publikacji: EN

Abstrakty

EN

To regulate reproduction in mammals, internal and external status is communicated to the hypothalamic-pituitary-gonadal axis via a coordinated balance of stimulatory and inhibitory neurochemical systems. This review describes the neuroanatomical organization of the kisspeptin system in the hypothalamus, and summarizes its role in signaling hypothalamic GnRH neurons, namely: multimodal actions of kisspeptin in the control of GnRH secretion during different physiological states of animals; involvement of kisspeptin in relaying metabolic information to hypothalamic GnRH neurons; neurobiological mechanisms underlying kisspeptin activation of GnRH neurons during puberty onset; effect of gonadal steroids in the early postnatal period in rodents on kisspeptin expression in the hypothalamus and gonadotropin secretion in adults; effect of photoperiod and metabolic cues on the activation/inhibition of hypothalamic-pituitary-gonadal axis in seasonally breeding species by kisspeptin.

• Wydawca: -
• Czasopismo: Journal of Animal and Feed Sciences
• Rocznik: 2012
• Tom: 21
• Numer: 3
• Opis fizyczny: p.397-424,fig.,ref.

Twórcy

autor

Przekop E.

• Department of Neuroendocrinology, Kielanowski Institute of Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jabłonna, Poland

autor

Ciechanowska M.

• Department of Pharmacology and Toxicology, General Karol Kaczkowski Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland

Bibliografia

• Adams V.L., Goodman R.L., Salm A.K., Coolen L.M., Karsch F.J., Lehman M.N., 2006. Morphological plasticity in the neural circuitry responsible for seasonal breeding in the ewe. Endocrinology 147, 4843-4851
• Agata R., Matsuzaki T., Iwasa T., Kiyokawa M., Tanaka N., Kuwahara A., Yasui T., Irahara M., 2009. Hypothalamic ghrelin suppress pulsatile secretion of luteinizing hormone via β-endorphin in ovariectomized rats. Neuroendocrinology 90, 364-370
• Ahima R.S., Hileman S.M., 2000. Postnatal regulation of hypothalamic neuropeptide Y expression by leptin: implications for energy balance and body weight regulation. Regul. Peptides 92, 1-7
• Amstalden M., Coolen L.M., Hemmerle A.M., Billings H.J., Connors J.M., Goodman R.L., Lehman M.N., 2010a. Neurokinin 3 receptor immunoreactivity in the septal region, preoptic area and hypothalamus of the female sheep: colocalisation in neurokinin В cells of the arcuate nucleus but not in gonadotropin-releasing hormone neurons. J. Neuroendocrinol. 22, 1-12
• Amstalden M., Redmond J.S., Baez-Sandoval G.M., Spell M., Spencer T.E., Lents C.A., Williams G.L., 2010b. Kiss-1 gene expression in the arcuate nucleus increases during activation of pulsatile release of LH in maturing ewe lambs. In: Proceedings of the 7th International Congress of Neuroendocrinology. Rouen (France), Abstr., p.80
• Backholer K., Bowden M., Gamber K., Bjorback C., Igbal J., Clarke I.J., 2010a. Melanocortins mimic the effects of leptin to restore reproductive function in lean hypogonadotropic ewes. Neuroendocrinology 91, 27-40
• Backholer K., Smith J.T., Clarke I.J., 2009. Melanocortins may stimulate reproduction by activated orexin neurons in the dorsomedial hypothalamus and kisspeptin neurons in the preoptic area of the ewe. Endocrinology 150, 5488-5497
• Backholer K., Smith J.T., Rao A., Pereira A., Igbal J., Ogawa S., Li C., Clarke I.J., 2010b. Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells. Endocrinology 151, 2233-2243
• Bateman H.L., Palisaul H.B., 2008. Disrupted female reproductive physiology following neonatal exposure to phytooestrogens or oestrogen specific ligands is associated with decreased GnRH activation and kisspeptin fiber density in the hypothalamus. Neurotoxicology 29, 988-997
• Bellefontain N., Hanchate N.K., Parkash J., Campagne C., deSeranno S., Clasadonte J., d’Anglemont de Tassigny X., Prevot V., 2011. Nitric oxide as key mediator of neuron-to-neuron and endothelia-to-glia communication involved in the neuroendocrine control of reproduction. Neuroendocrinology 93, 74-89
• Billings H.J., Connors J.M., Altman S.N., Hileman S.M., Halaskova I., Lehman M.N., Mc Manus C.J., Nestor C.C., Jacobs R.H., Goodman R.L., 2010. Neurokinin В acts via neurokinin-3 receptor in the retrochiasmatic area to stimulate luteininzing hormone secretion in sheep. Endocrinology 151, 3836-3846
• Briggs D.J., Andrews Z.B., 2011. Metabolic status regulates ghrelin function on energy homeostasis. Neuroendocrinology 93, 48-57
• Brown R.E., Imran S.A., Ur E., Wilkinson M., 2008. Kiss-1 mRNA in adipose tissue is regulated by sex hormones and food intake. Mol. Cell. Endocrinol. 281, 64-72
• Caraty A., Franceschini I., Hoffman G.E., 2010. Kisspeptin and the preovulatory gonadotropinreleasing hormone, luteinizing hormone surge in the ewe: basic aspects and potential applications in the control of ovulation. J. Neuroendocrinol. 22, 710-715
• Caraty A., Smith J.T., Lanet D., Ben Said S., Morrisay A., Congée J., Doughton B., Baril G., Briant C., Clarke I.J., 2007. Kisspeptin synchronizes preovulatory surges in cyclical ewes and causes ovulation in seasonally acyclic ewes. Endocrinology 148, 5258-5267
• Castellano J.M., Navarro V.M., Fernandez-Fernandez R., Castano J.P., Malagon M.N., Aguilar E., Dieguez C., Magui 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. 258, 75-83
• Castellano J.M., Navarro V.M., Fernandez-Fernandez R., et al., 2005. Changes in hypothalamic kiss 1 system and restoration of pubertal activation of the reproductive axis by kisspeptin undernutrition. Endocrinology 146, 3917-3925
• Castellano J.M., Roa J., Lugue R.M., Dieguez C., Aguilar E., Pinilla L., Tena-Sempere M., 2009. Kiss 1/kisspeptins and the metabolic control of reproduction: Physiologic roles and putative physiopathological implications. Peptides 30, 139-145
• Chalivoix S., Bagnolini A., Caraty A., Cognie J., Malpaux B., Dufourny L., 2010. Effects of photoperiod on kisspeptin neural populations of the ewe diencephalon in connection with reproductive function. J. Neuroendocrinol. 22, 110-118
• Chan Y.M., Broder-Fingert S., Seminara S.B., 2009a. Reproductive functions of kisspeptin and GPR54 across the life cycle of mice and men. Peptides 30, 42-48
• Chan Y.M., Broder-Fingert S., Wong K.M., Seminara S.B., 2009b. Kisspeptin/Gpr 54 - independent gonadotropin-releasing hormone activity in kiss 1 and Gpr 54 mutant mice. J. Neuroendocrinol. 21, 1015-1023
• Cheng G., Coolen L.M., Padmanabhan V., Goodman R.L., Lehman M.N., 2010. The kisspeptin/neurokinin/dynorphin (KNDy) cell population of the arcuate nucleus: sex differences and effects of prenatal testosterone in sheep. Endocrinology 151, 301-311
• Ciechanowska M., Łapot M., Mateusiak K., Przekop F., 2010. Neuroendocrine regulation of GnRH release, and expression of GnRH and GnRH receptor (GnRH-R) genes in the hypothalamicpituitary unit in different physiological states. Reprod. Biol. 10, 85-124
• Ciofi P., Leray D., Tramu G., 2006. Sexual dimorphism in the organization of the rat hypothalamic infundibular area. Neuroscience 141, 1731-1745
• Clarke I.J., Backholer K., Tilbrook A.J., 2005. Y2 receptor-selective agonist delays the estrogeninduced luteinizing hormone surge in ovariectomized ewes, but Y1 receptor selective agonist stimulates voluntary food intake. Endocrinology 146, 769-775
• Clarke I.J., Scaramuzzi R.J., Short R.V., 1997. Ovulation in prenatally androgemized ewes. J. Endocrinol. 73, 385-389
• Clarkson J., Boon W.C., Simpson E.R., Herbison A.E., 2009. Postnatal development of an estradiolkisspeptin feedback mechanism implicated in puberty onset. Endocrinology 150, 3214-3220
• Clarkson J., D’Anglemont de Tassigny X., Moreno A.S., Colledge W.H., Herbison A.E., 2007. Kisspeptin GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge. J. Neurosci. 28, 8691-8697
• Clarkson J., Han K., Lin X., Lee K., Herbison A.E., 2010. Neurobiological mechanisms underlying kisspeptin activation of gonadotropin-releasing hormone (GnRH) neurons at puberty. Mol. Cell. Endocrinol. 324, 45-50
• Corander M.P., Challis B.G., Thompson E.L. et al., 2010. The effect of neurokinin В upon gonadotrophin release in male rodents. J. Neuroendocrinol. 22, 181-187
• Corbier P., 1985. Sexual differentiation of positive feedback: effect of hour of castration at birth on estradiol-induced luteinizing hormone secretion in immature male rat. Endocrinology 116, 142-147
• D’Anglemont de Tassigny X., Ackroyd K.J., Chatzidaki E.E., Colledge W.H., 2010. Kisspeptin and NMDA signaling in the neuroendocrine mouse brain. In: Proceedings of the 7th International Congress of Neuroendocrinology. Rouen (France), Abstr., p. 86
• Donato J.R., Cravo R.M., Frazao R., Elias C.F., 2011. Hypothalamic sites of leptin action linking metabolism and reproduction. Neuroendocrinology 93, 9-18
• Dungan H.M., Gottsch M.L., Zeng H., Gragerov A., Bergmann J.E., Vassilatis D.K., Clifton D.K., Steiner R.A., 2007. The role of kisspeptin-GPR54 signaling in the tonic regulation and surge release of gonadotropin-releasing hormone/luteinizing hormone. J. Neurosci. 27, 12088- 12095
• Felip A., Zanury S., Pineda R., Pinilla L., Carrillo M., Tena-Sempere M., Gomez A., 2009. Evidence for two distinct kiss genes in non-placental vertebrates that encode kisspeptin with different gonadotropin-releasing activities in fish and mammals. Mol. Cell. Endocrinol. 312, 61-71
• Fernandez-Fernandez R., Martini A.C., Navarro V.M., Castellano J.M., Dieguez C., Aguilar E., Pinilla L., Tena-Sempere M., 2006. Novel signals for the intergration of energy balance and reproduction. Mol. Cell. Endocrinol. 254/255, 127-132
• Foradori C.D., Amstalden M., Goodman R.L., Lehman M.N., 2006. Colocalization of dynorphin A and neurokinin В immunoreactivity in the arcuate nucleus and median eminence. J. Neuroendocrinol. 18, 534-544
• Forbes S., Li X.F., Kinsey-Jones J., O’Byrne K., 2009. Effects of grelin on kisspeptin mRNA expression in the hypothalamic medial preoptic area and pulsatile luteinizing hormone secretion in the female rat. Neurosci. Lett. 460, 143-147
• Foster D.L., Jackson L.M., Padmanabhan V., 2006. Programming of GnRH feedback controls timing puberty and adult reproductive activity. Mol. Cell. Endocrinol. 255, 109-119
• George J.T., Millar R.P., Anderson R.A., 2011. Hypothesis: kisspeptin mediates male hypogonadism in obesity and type 2 diabetes. Neuroendocrinology 91, 302-307
• Glidewell-Kenney C., Hurley L.A., Pfaff L., Weiss J., Levine J.E., Jameson J.L., 2007. Nonclassical estrogen receptor α signaling mediates negative feedback in the female mouse reproductive axis. Proc. Nat. Acad. Sci. USA 104, 8173-8177
• Goodman R.L., Jansen H.T., Billings H.J., Coolen L.M., Lehman M.N., 2010. Neural systems mediating seasonal breeding in the ewe. J. Neuroendocrinol. 22, 674-681
• Goodman R.L., Lehman M.N., Smith J.T. et al., 2007. Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin В. Endocrinology 148, 5752-5760
• Goodman R.L., Robinson J.E., Kendrick K.M., Dyer R.G., 1995. Is the inhibitory action of estradiol on luteinizing hormone pulse frequency in anestrous ewes mediated by noradrenergic neurons in the preoptic area? Neuroendocrinology 61, 284-292
• Gottsch M.N., Navarro V.M., Zhao Z., Glidewell-Kenney C., Weiss J., Jameson J.C., Clifton D.K., Levine J.E., Steiner R.A., 2009. Regulation of kiss 1 and dynorphin gene expression in the murine brain by classical and nonclassical estrogen receptor pathways. J. Neurosci. 29, 9390-9395
• Greives T.J., Mason A.O., Levine J., Ketterson E.D., Kriegsfeld L.I., Demas G.E., 2007. Environmental control of kisspeptin: implications for seasonal reproduction. Endocrinology 148, 1158-1166
• Han S.K., Gottsch M.L., Lee K.J., Popa S.M., Smith J.T., Jakawich S.K., Clifton D.K., Steiner R.A., Herbison A.E., 2005. Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. J. Neurosci. 25, 11349-11356
• Handa R.J., Gorski R.A., 1985. Alternations in the onset of ovulatory failure and gonadotropin secretion following steroid administration to lightly androgenized female rats. Biol. Reprod. 32, 248-256
• Herbison A.E., D’Anglemont de Tassigny X., Doran J., Colledge W.H., 2010. Distribution and postnatal development of GPR 54 gene expression in the mouse brain and gonadotropinreleasing hormone neurons. Endocrinology 151, 312-321
• Homma T., Sakakibara M., Yamada S. et al., 2009. Significance of neonatal testicular sex steroids to determinizm anteroventral periventricular kisspeptin neurons and the GnRH/LH surge system in male rats. Biol. Reprod. 81, 1216-1225
• Irwing M.S., Fraley G.S., Smith J.T., Acohido B.V., Popa S.M., Cunningham M.J., Gottsch M.L., Clifton D.K., Steiner R.A., 2004. Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of kiss-1 mRNA in the male rat. Neuroendocrinology 80, 264-272
• Kauffman A.S., Clifton D.K., Steiner R.A., 2007a. Emerging ideas about kisspeptin: GPR 54 signaling in the neuroendocrine regulation of reproduction. Trends Neurosci. 30, 504-511
• Kauffman A.S., Gottsch M.L., Roa J., Byquist A.C., Crown A., Clifton D.K., Hoffman G.E., Steiner R.A., Tena-Sempere M., 2007b. Sexual differentiation of kiss 1 gene expression in the brain of the rat. Endocrinology 148, 1774-1783
• Kauffman A.S., Navarro V.M., Clifton D.K., Steiner R.A., 2009. Sex differences in the regulation of kiss 1/NKВ neurons in juvenile mice: implications for the timing of puberty. Amer. J. Physiol.- Endocrinol. Met. 297, 1212-1221
• Keen K.L., Wagner F.H., Bloom S.R., Ghatei M.A., Terasawa E., 2008. An increase in kisspeptin-54 release occurs with the pubertal increase in luteinizing hormone-releasing hormone-1 release in the stalk-median eminence female rhesus monkeys in vivo. Endocrinology 149, 4151-4157
• Kim G.L., Dhillon S.S., Belsham D.D., 2010. Kisspeptin directly regulates NPY synthesis and secretion via ERK ½ and p 38MAPK signaling pathways in an NPY-secreting hypothalamic cell line. In: Proceedings of the 7th International Congress of Neuroendocrinology. Rouen (France), Abstr. p. 104
• Kim W., Jessen H.M., Auger A.P., Terasawa E., 2009. Postmenopausal increase in kiss-1, GPR 54, and luteinizing hormone-releasing hormone (LHRH) mRNA in the basal hypothalamus of female rhesus monkeys. Peptides 30, 103-110
• Kinoshita M., Tsukamura H., Adachi S. et al., 2005. Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats. Endocrinology 146, 4431-4436
• Kotani M., Detheus M., Vandenbogaerde A., Communi D., Vanderwinden F., Blanpain C., Schiffman S.N., Vassart G., Parmentier M., 2001. The metastasis suppressor gene kiss-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR-54. J. Biol. Chem. 276, 34631-34636
• Kurose Y., Igbal J., Rao A., Murata Y., Hasegawa Y., Terashima Y., Kojina M., Kangawa K., Clarke I.J., 2005. Changes in the expression of the genes for the leptin receptor and growth hormone-releasing peptide/ghrelin receptor in the hypothalamic arcuate nucleus with long term manipulation of adiposity by dietary means. J. Neuroendocrinol. 17, 331-340
• Le Corre S., Chemineau P., 1993. Control of photoperiodic inhibition of luteinizing hormone secretion by dopaminergic and serotoninergic systems in ovariectomized Ile-de-France ewes supplemented with estradiol. J. Reprod. Fertil. 97, 367-373
• Lee Y.R., Tsunekawa K., Moon M.J., Um H.N. et al., 2009. Molecular evolution of multiple forms of kisspeptins and GPR 54 receptors in vertebrates. Endocrinology 150, 2837-2846
• Lehman M.N., Coolen L.M., Goodman R.L., 2010. Minireviews: kisspeptin/neurokinin В/dynorphin (KNDy) cells of the arcuate nucleus; a central notre in the control of gonadotropin-releasing hormone secretion. Endocrinology 151, 3479-3489
• Levis D., Freemom D.A., Dark J., Wynne-Edwards K.E., Zucker I., 2002. Photoperiodic control of oestrous cycles in Syrian hamsters: mediation by the mediobasal hypothalamus. J. Neuroendocrinol. 14, 294-299
• Malpaux B., Daveau A., Maurice-Mandon F., Duarte G., Chemineau P., 1998. Evidence that melatonin acts in the premammillary hypothalamic area to control reproduction in the ewes presence of binding sites and stimulation of luteinizing hormone secretion by in situ microimplant delivery. Endocrinology 139, 1508-1516
• Mason A.O., Greives T.J., Scotti M.A., Levine J., Frommeyer S., Ketterson E.D., Demas G.E., Kriegsfeld L.I., 2007. Suppression of kisspeptin expression and gonadal axis sensitivity following exposure to inhibitory day lengths in female Siberian hamsters. Hormone Behav. 52, 492-498
• Maywood E.S., Bittman E.L., Hastings M.H., 1996. Lesions of the melatonin-and androgenresponsive tissue of the dorsomedial nucleus of the hypothalamus block the gonadal response of male Syrian hamsters to programmed infusion of melatonin. Biol. Reprod. 54, 470-477
• Messager S., Chatzidaki E.E., Ma D. et al., 2005. Kisspeptin directly stimulates gonadotropinreleasing hormone release via G protein-coupled receptor 54. Proc. Nat. Acad. Sci. USA 102, 1761-1766
• Muir A.I., Chamberlain L., Elshourbagy N.A. et al., 2001. AXOR 12, a novel human G proteincoupled receptors activated by the peptide kiss-1. J. Biol. Chem. 276, 28969-28975
• Navarro V.M., Castellano J.M., Fernandez-Fernandez R., Barreiro M.L., Roa J., Sanchez-Criado J.E., Aouilar E., Dieguez C., Pinilla L., Tena-Sempere M., 2004. Developmental and hormonally regulated messenger ribonucleic acid expression of kiss-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing hormone activity of kiss-1 peptide. Endocrinology 145, 4565-4572
• Navarro V.M., Castellano J.M., Fernandez-Fernandez R., Tovar S., Mayen A., Nogueiras R., Vazquez C., Pinilla L., Tena-Sempere M., 2005a. Characterization of the potent luteinizing hormonereleasing hormone activity of kiss-1 peptide, the natural ligand of GPR54. Endocrinology 146, 156-163
• Navarro V.M., Castellano J.M., Fernandez-Fernandez R. et al., 2005b. Effect of kiss-1 peptide, the natural ligand of GPR-54 on follicle stimulating hormone secretion in the rat. Endocrinology 146, 1689-1697
• Navarro V.M., Gottsch M.L., Chavkin C., Okamura H., Clifton D.K., Steiner R.A., 2009. Regulation of gonadotropin-releasing hormone secretion by kisspeptin/neurokinin В neurons in the arcuate nucleus of the mouse. J. Neurosci. 29, 11859-11866
• Oakley A.E., Clifton D.K., Steiner R.A., 2009. Kisspeptin signaling in the brain. Endocr. Rev. 30, 731-743
• Ohtaki T., Shintani Y., Honda S. et al., 2001. Metastasis suppressor gene kiss-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 411, 613-617
• Ojeda S.R., Skinner M.N., 2006. Puberty in the rat. In: J.D. Neill (Editor). The Physiology of Reproduction. Academic Press/Elsevier. San Diego, CA, pp. 2061-2126
• Paul M.J., Pytel L.M., Freeman D.A., Galang J., Prendergast B.J., 2009a. Photic and nonphotic seasonal cues differentially engage hypothalamic kisspeptin and RF-amide-related peptide mRNA expression in Siberian hamsters. J. Neuroendocrinol. 21, 1007-1014
• Paul M.J., Schwartz W.J., Prendergast B.J., 2009b. Intermediate-duration day lengths unmask reproductive responses to nonphotic environmental cues. Amer. J. Physiol. 296, R1613-R1619
• Pielecka-Fortuna J., Moenter S.M., 2010. Kisspeptin increases γ-aminobutyric acidergic and glutamatergic transmission directly to gonadotropin-releasing hormone neurons in an estradioldependent manner. Endocrinology 151, 291-300
• Pineda R., Garcia-Galiano D., Rosewei A., Romero M., Sanchez-Garrido M.A., Ruiz-Pino F., Morgan K., Pinilla L., Millar R.P., Tena-Sempere M., 2010. Critical role of kisspeptin in female puberty and preovulatory gonadotropin surges as revealed by novel antagonist. Endocrinology 151, 722-730
• Plant T.M., 2006. The male monkey as a model for the study of the neuroendocrinology of puberty onset in man. Mol. Cell. Endocrinol. 255, 97-102
• Plant T.M., Ramaswamy S., Dipietro M.J., 2006. Repetive activation of hypothalamic G-protein coupled receptor 54 with intravenous pulses of kisspeptin in juvenile monkey (Macaza mulata) elicits a sustained train of gonadotropin-releasing hormone discharges. Endocrinology 147, 1007-1013
• Plant T.M., Witchel S.M., 2006. Puberty in non-human primates and humans. In: J.D. Neill (Editor). Physiology of Reproduction. 3rd Edition. Knobil and Neill’s. Amsterdam, Elsevier, pp. 2177-2230
• Pompolo S., Pereira A., Estrada K.M., Clarke I.J., 2006. Colocalization of kisspeptin and gonadotropin-releasing hormone in the ovine brain. Endocrinology 147, 804-810
• Prendergast B.J., 2010. MT 1 melatonin receptors mediate somatic, behavioral and reproductive neuroendocrine responses to photoperiod and melatonin in Siberian hamsters (Phodopus sungorus). Endocrinology 151, 714-721
• Quennel J.H., Mulligan A.C., Tups A., Liu X., Phipps S.J., Kemp C.J., Herbison A.E., Grattan D.R., Anderson G.M., 2009. Leptin indirectly regulates gonadotropin releasing hormone neuronal function. Endocrinology 150, 2805-2812
• Ramaswamy S., Guerriero K.A., Gibbs R.B., Plant T.M., 2008. Structural interactions between kisspeptin and GnRH neurons in the medial basal hypothalamus of the male rhesus monkey (Macaca mulata) as revealed by double immunofluoroscence and confocal microscopy. Endocrinology 149, 4387-4395
• Revel F.G., Ansel L., Klosen P., Saboureasu M., Pevet P., Mikkelsen J.D., Simonneaux V., 2007. Kisspeptin: a key link to seasonal breeding. Rev. Endocr. Metab. Disord. 8, 57-65
• Revel F.G., Saboureau M., Masson-Pevet M., Pevet P., Mikkelsen J.D., Simonneaux X.V., 2006. Kisspeptin mediates photoperiodic control of reproduction hamsters. Curr. Biol. 16, 1730-1735
• Richard N., Galmiche G., Corvaisier S., Caraty A., Kottler M.L., 2008. Kiss-1 and GPR 54 gene are co-expressed in rat gonadotrophs and differentially regulated in vivo by oestradiol and gonadotrophin-releasing hormone. J. Neuroendocrinol. 20, 381-393
• Roa J., Garcia-Galiano D., Castellano J.M., Gaytan F., Pinilla L., Tena-Sempere M., 2010. Metabolic control of puberty onset: new players, new mechanisms. Mol. Cell. Endocrinol. 324, 87-94
• Roa J., Wigo E., Garcia-Galiano D., Castelonzo J.M., Navarro V.M., Pineda R., Dieguez C., Aguilar E., Pinilla L., Tena-Sempere M., 2008. Desensitization of gonadotropin responses to kisspeptin in the female rat: analysis of LH and FSH secretion at different developmental and metabolic states. Amer. J. Physiol. 294, E1088-E1096
• Robinson J.E., Forsdike R.A., Taylor J.A., 1999. In utero exposure of female lambs to testosterone reduces the sensitivity of the gonadotropin-releasing hormone neuronal network to inhibition by progesterone. Endocrinology 140, 5797-5805
• Roseweir A.K., Kauffman A.S., Smith J.T. et al., 2009. Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation. J. Neurosci. 29, 3920-3929
• Roseweir A., Kauffman A., Smith J.T. et al., 2010. Kisspeptin antagonists reveal kisspeptin’s neuroendocrine role in reproduction. In: Proceedings of the 7th International Congress of Neuroendocrinology. Rouen (France), Abstr. p.60
• Roseweir A., Millar R.P., 2009. The role of kisspeptin in the control of gonadotropin secretion. Hum. Reprod. Update 15, 203-212
• Sandoval-Guzman T., Rance N.E., 2004. Central injection of senktil, an NK3 receptor agonist, or neuropeptide Y inhibits LH secretion and induces different patterns of for expression in the rat hypothalamus. Brain Res. 1026, 307-312.
• Scott C.J., Clarke I.J., 1993. Inhibition of luteinizing hormone secretion in ovariectomized ewes during the breeding season by γ-aminobutyric acid (GABA) is mediated by GABA-A receptors, but not GABA-B receptors. Endocrinology 132, 1789-1796
• Seminara S.B., Dipietro M.J., Ramaswamy S., Crowley Jr. W.F., Plant T.M., 2006.Continuous human metastin 45-54 infusion desensitizes G-protein-coupled receptor 54-induced gonadotropinreleaseing hormone release monitored indirectly in the juvenile male rhesus monkey (Macaca mulata): finding with therapeutic implications. Endocrinology 147, 2122-2126
• Seminara S.B., Messager S., Chatzidaki E.E. et al., 2003. The GPR54 gene as a regulator of puberty. N. Engl. J. Med. 349, 1614-1627
• Shahab M., Mastronardi C., Seminara S.B., Crowley W.F., Ojeda S.R., Plant T.M., 2005. Increased hypothalamic GPR 54 signaling: a potential mechanism for initiation of puberty in primates. Proc. Nat. Acad. Sci. USA 102, 2129-2134
• Skinner D.C., Herbison A.E., 1997. Effects of photoperiod on estrogen receptor, tyrosine hydroxylase, neuropeptide Y, and β-endorphin immunoreactivity in the ewe hypothalamus. Endocrinology 138, 2585-2595
• Smith J.T., Acohido B.V., Clitton D.K., Steiner R.A., 2006a. Kiss-1 neurons are direct targets for leptin in the db/db mouse. J. Neuroendocrinol. 18, 298-303
• Smith J.T., Clay C.M., Caraty A., Clarke I.J., 2007. Kiss 1 messenger ribonucleic acid expression in the hypothalamus of the ewe is regulated by sex steroids and season. Endocrinology 148, 1150-1157
• Smith J.T., Clifton D.K., Steiner R.A., 2006b. Regulation of neuroendocrine reproductive axis by kisspeptin-GPR 54 signaling. Reproduction 131, 623-630
• Smith J.T., Coolen L.M., Kriegsfeld L.J. et al., 2008a. Variation in kisspeptin and RF amide-related peptide (RFRP-3) expression and terminal connections to gonadotropin-releasing hormone neurons in the brain: a novel medium for seasonal breeding in the sheep. Endocrinology 149, 5770-5782
• Smith J.T., Li Q., Pereira A., Clarke I.J., 2009a. Kisspeptin neurons in the ovine arcuate nucleus and preoptic area involved in the preovulatory luteinizing hormone surge. Endocrinology 150, 5530-5538
• Smith J.T., Popa S.M., Clifton D.K., Hoffman G.E., Steiner R.A., 2006c. Kiss 1 neurons in the forebrain as central processors for generating the preovulatory luteinizing hormone surge. J. Neurosci. 26, 6687-6694
• Smith J.T., Rao A., Pereira A., Caraty A., Millar R.P., Clarke I.J., 2008b. Kisspeptin is present in ovine hypophysial blood but does not increase during the preovulatory luteinizing hormone surge evidence that gonadotropes are not direct targets of kisspeptin in vivo. Endocrinology 149, 1951-1959
• Smith J.T., Salch S.N.H., Clarke I.J., 2009b. Seasonal and cyclical change in the luteinizing hormone response to kisspeptin in the ewe. Neuroendocrinology 90, 283-291
• Smith J.T., Shahab M., Millar R., Clarke I.J., 2010. Kisspeptin antagonist reveals an important role for kisspeptin in the generation of the estrogen induced GnRH/LH surge in the ewe. In: Proceedings of the 7th International Congress of Neuroendocrinology. Rouen (France), Abstr. p. 212
• Terasawa E., Kurian J.R., Guerriero K.A., Kenealy B.P., Hutz E.D., Keen K.L., 2010. Recent discovery on the control of gonadotropin-releasing hormone neurons in nonhuman primates. J. Neuroendocrinol. 22, 630-638
• Thompson E.I., Petterson M., Murphy K.G., Smith K.I., Dhillo W.S., Todd J.F., Ghatei M.A., Bloom J.F., 2004. Central and peripheral administration of kisspeptin-10 stimulates the hypothalamicpituitary-gonadal axis. J. Neuroendocrinol. 16, 850-858
• Thornton J.E., Cheung C.C., Clifton D.K., Steiner R.A., 1997. Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice. Endocrinology 138, 5063-5066
• Topaloglu A.K., Kotan D.D., Yuksel B., 2010. Neurokinin В signaling in human puberty. J. Neuroendocrinol. 22, 765-770
• Tovar S., Vazquez M.J., Navarro V.M. et al., 2006. Effects of single or repeated intravenous administration of kisspeptin upon dynamic LH secretion in conscious male rat. Endocrinology 147, 2696-2704
• Wagner G.C., Johnstone J.D., Clarke I.J., Lincoln G.A., Hazlerigg D.G., 2008. Redefining the limits of day length responsiveness in a seasonal mammal. Endocrinology 149, 32-39
• Watanabe H., Schioth H.B., Wikberg J.E., Suda T., 1999. The melanocortin 4 receptor mediates leptin stimulation of luteinizing hormone and prolactin surges in steroid-primed ovariectomized rats. Biochem. Biophys. Res. Commun. 257, 860-864
• West A., Vojta P.J., Welch D.R., Weisman B.E., 1998. Chromosome localization and genomic structure of the kiss-1 metastasis suppressor gene (Kiss1). Genomics 54, 145-148
• Wu M., Dumalska I., Morozova E., Van Den Pol A.N., 2009. Gonadotropin inhibitory basal forebrain V Glut 2 - gonadotropin-releasing hormone neurons via direct postsynaptic mechanism. J. Physiol. 587, 1401-1411
• Xiong J.J., Karsch F.J., Lehman M.N., 1997. Evidence for seasonal plasticity in the gonadotropinreleasing hormone (GnRH) system in the ewe: changes in synaptic inputs onto GnRH neurons. Endocrinology 138, 1240-1250
• Zhang C., Bosch M.A., Rennekleiv O.K., Kelly M.J., 2009. γ-aminobutyric acid В receptor mediated inhibition of gonadotropin-releasing hormone neurons is suppressed by kisspeptin-G proteincoupled receptor 54 signaling. Endocrinology 150, 2388-2394
• Zhang C., Roepke T.A., Kelly M.J., Ronnekleiv O.K., 2008. Kisspeptin depolarizes gonadotropinreleasing hormone neurons through activation of TRPC-like cationic channels. J. Neurosci. 28, 4423-4434