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Sex Steroid Regulation of Kisspeptin Circuits

  • Jeremy T. Smith
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 784)

Abstract

Kisspeptin cells appear to be the “missing link,” bridging the divide between levels of gonadal steroids and feedback control of gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin neurons are important in the generation of both sex steroid negative and estrogen positive feedback signals to GnRH neurons, the former being involved in the tonic regulation of GnRH secretion in males and females and the latter governing the preovulatory GnRH/luteinizing hormone (LH) surge in females. In rodents, kisspeptin-producing cells populate the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC), and estrogen regulation of kisspeptin has been extensively studied in these regions. Kisspeptin cells in the ARC appear to receive and forward signals applicable to negative feedback regulation of GnRH. In the female rodent AVPV, kisspeptin cells are important for positive feedback regulation of GnRH and the preovulatory LH surge. In sheep and primates, a rostral population of kisspeptin cells is located in the dorsolateral preoptic area (POA) as well as the ARC. Initial studies showed kisspeptin cells in the latter were involved in both the positive and negative feedback regulation of GnRH. Interestingly, further studies now suggest that kisspeptin cells in the ovine POA may also play an important role in generating estrogen positive feedback. This chapter discusses the current consensus knowledge regarding the interaction between sex steroids and kisspeptin neurons in mammals.

Keywords

GnRH Neuron GnRH Secretion Mediobasal Hypothalamus Estrogen Positive Feedback Kiss1 mRNA 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Moore CR, Price D (1932) Gonadal hormone functions and the reciprocal influence between gonads and hypophysis, with its bearing on sex hormone antagonism. Am J Anat 50:13–71CrossRefGoogle Scholar
  2. 2.
    Herbison AE, Theodosis DT (1992) Localization of oestrogen receptors in preoptic neurons containing neurotensin but not tyrosine hydroxylase, cholecystokinin or luteinizing hormone-­releasing hormone in the male and female rat. Neuroscience 50:283–298PubMedCrossRefGoogle Scholar
  3. 3.
    Shivers BD, Harlan RE, Morrell JI, Pfaff DW (1983) Absence of oestradiol concentration in cell nuclei of LHRH-immunoreactive neurones. Nature 304:345–347PubMedCrossRefGoogle Scholar
  4. 4.
    Skinner DC, Caraty A, Allingham R (2001) Unmasking the progesterone receptor in the preoptic area and hypothalamus of the ewe: no colocalization with gonadotropin-releasing neurons. Endocrinology 142:573–579PubMedCrossRefGoogle Scholar
  5. 5.
    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 145:4073–4077PubMedCrossRefGoogle Scholar
  6. 6.
    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 80:264–272PubMedCrossRefGoogle Scholar
  7. 7.
    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 320:383–388PubMedCrossRefGoogle Scholar
  8. 8.
    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 USA 102:2129–2134PubMedCrossRefGoogle Scholar
  9. 9.
    Patterson M, Murphy KG, Thompson EL, Patel S, Ghatei MA, Bloom SR (2006) Administration of kisspeptin-54 into discrete regions of the hypothalamus potently increases plasma luteinising hormone and testosterone in male adult rats. J Neuroendocrinol 18:349–354PubMedCrossRefGoogle Scholar
  10. 10.
    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 25:11349–11356PubMedCrossRefGoogle Scholar
  11. 11.
    Pielecka-Fortuna J, Chu Z, Moenter SM (2008) Kisspeptin acts directly and indirectly to increase gonadotropin-releasing hormone neuron activity and its effects are modulated by estradiol. Endocrinology 149:1979–1986PubMedCrossRefGoogle Scholar
  12. 12.
    Clarkson J, Herbison AE (2006) Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons. Endocrinology 147:5817–5825PubMedCrossRefGoogle Scholar
  13. 13.
    Kinoshita M, Tsukamura H, Adachi S, Matsui H, Uenoyama Y, Iwata K, Yamada S, Inoue K, Ohtaki T, Matsumoto H, Maeda K (2005) Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats. Endocrinology 146:4431–4436PubMedCrossRefGoogle Scholar
  14. 14.
    Smith JT, Coolen LM, Kriegsfeld LJ, Sari IP, Jafarzadehshirazi MR, Maltby M, Bateman K, Goodman RL, Tilbrook AJ, Ubuka T, Bentley GE, Clarke IJ, Lehman MN (2008) Variation in kisspeptin and RFamide-related peptide (RFRP) expression and terminal connections to gonadotropin-releasing hormone neurons in the brain: a novel medium for seasonal breeding in the sheep. Endocrinology 149:5770–5782PubMedCrossRefGoogle Scholar
  15. 15.
    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 152:1001–1012PubMedCrossRefGoogle Scholar
  16. 16.
    Smith JT, Li Q, Pereira A, Clarke IJ (2009) Kisspeptin neurons in the ovine arcuate nucleus and preoptic area are involved in the preovulatory luteinizing hormone surge. Endocrinology 150:5530–5538PubMedCrossRefGoogle Scholar
  17. 17.
    Dungan HM, Gottsch ML, Zeng H, Gragerov A, Bergmann JE, Vassilatis DK, Clifton DK, Steiner RA (2007) The role of kisspeptin-GPR54 signaling in the tonic regulation and surge release of gonadotropin-releasing hormone/luteinizing hormone. J Neurosci 27:12088–12095PubMedCrossRefGoogle Scholar
  18. 18.
    Kauffman AS, Park JH, McPhie-Lalmansingh AA, Gottsch ML, Bodo C, Hohmann JG, Pavlova MN, Rohde AD, Clifton DK, Steiner RA, Rissman EF (2007) The kisspeptin receptor GPR54 is required for sexual differentiation of the brain and behavior. J Neurosci 27:8826–8835PubMedCrossRefGoogle Scholar
  19. 19.
    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 USA 102:1761–1766PubMedCrossRefGoogle Scholar
  20. 20.
    Kauffman AS, Gottsch ML, Roa J, Byquist AC, Crown A, Clifton DK, Hoffman GE, Steiner RA, Tena-Sempere M (2007) Sexual differentiation of Kiss1 gene expression in the brain of the rat. Endocrinology 148:1774–1783PubMedCrossRefGoogle Scholar
  21. 21.
    Smith JT, Popa SM, Clifton DK, Hoffman GE, Steiner RA (2006) Kiss1 neurons in the forebrain as central processors for generating the preovulatory luteinizing hormone surge. J Neurosci 26:6687–6694PubMedCrossRefGoogle Scholar
  22. 22.
    Greives TJ, Mason AO, Scotti MA, Levine J, Ketterson ED, Kriegsfeld LJ, Demas GE (2007) Environmental control of kisspeptin: implications for seasonal reproduction. Endocrinology 148:1158–1166PubMedCrossRefGoogle Scholar
  23. 23.
    Revel FG, Ansel L, Klosen P, Saboureau M, Pevet P, Mikkelsen JD, Simonneaux V (2007) Kisspeptin: a key link to seasonal breeding. Rev Endocr Metab Disord 8:57–65PubMedCrossRefGoogle Scholar
  24. 24.
    Clarkson J, d’Anglemont de Tassigny X, Colledge WH, Caraty A, Herbison AE (2009) Distribution of kisspeptin neurones in the adult female mouse brain. J Neuroendocrinol 21:673–682PubMedCrossRefGoogle Scholar
  25. 25.
    Adachi S, Yamada S, Takatsu Y, Matsui H, Kinoshita M, Takase K, Sugiura H, Ohtaki T, Matsumoto H, Uenoyama Y, Tsukamura H, Inoue K, Maeda KI (2007) Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats. J Reprod Dev 53:367–378PubMedCrossRefGoogle Scholar
  26. 26.
    Estrada KM, Clay CM, Pompolo S, Smith JT, Clarke IJ (2006) Elevated KiSS-1 expression in the arcuate nucleus prior to the cyclic preovulatory gonadotrophin-releasing hormone/luteinising hormone surge in the ewe suggests a stimulatory role for kisspeptin in oestrogen-positive feedback. J Neuroendocrinol 18:806–809PubMedCrossRefGoogle Scholar
  27. 27.
    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 148:1150–1157PubMedCrossRefGoogle Scholar
  28. 28.
    Franceschini I, Lomet D, Cateau M, Delsol G, Tillet Y, Caraty A (2006) Kisspeptin immunoreactive cells of the ovine preoptic area and arcuate nucleus co-express estrogen receptor alpha. Neurosci Lett 401:225–230PubMedCrossRefGoogle Scholar
  29. 29.
    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 149:4387–4395PubMedCrossRefGoogle Scholar
  30. 30.
    Rometo AM, Krajewski SJ, Voytko ML, Rance NE (2007) Hypertrophy and increased kisspeptin gene expression in the hypothalamic infundibular nucleus of postmenopausal women and ovariectomized monkeys. J Clin Endocrinol Metab 92:2744–2750PubMedCrossRefGoogle Scholar
  31. 31.
    Wintermantel TM, Campbell RE, Porteous R, Bock D, Grone HJ, Todman MG, Korach KS, Greiner E, Perez CA, Schutz G, Herbison AE (2006) Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility. Neuron 52:271–280PubMedCrossRefGoogle Scholar
  32. 32.
    Yeo SH, Herbison AE (2011) Projections of arcuate nucleus and rostral periventricular kisspeptin neurons in the adult female mouse brain. Endocrinology 152:2387–2399PubMedCrossRefGoogle Scholar
  33. 33.
    Clarkson J, Herbison AE (2011) Dual phenotype kisspeptin-dopamine neurones of the rostral periventricular area of the third ventricle project to gonadotrophin-releasing hormone neurones. J Neuroendocrinol 23:293–301PubMedCrossRefGoogle Scholar
  34. 34.
    Backholer K, Smith JT, Clarke IJ (2009) Melanocortins may stimulate reproduction by activating orexin neurons in the dorsomedial hypothalamus and kisspeptin neurons in the preoptic area of the ewe. Endocrinology 150:5488–5497PubMedCrossRefGoogle Scholar
  35. 35.
    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 149:3926–3932PubMedCrossRefGoogle Scholar
  36. 36.
    Smith JT (2009) Sex steroid control of hypothalamic Kiss1 expression in sheep and rodents: comparative aspects. Peptides 30:94–102PubMedCrossRefGoogle Scholar
  37. 37.
    Shughrue PJ, Lane MV, Merchenthaler I (1997) Comparative distribution of estrogen receptor-­alpha and -beta mRNA in the rat central nervous system. J Comp Neurol 388:507–525PubMedCrossRefGoogle Scholar
  38. 38.
    Simerly RB (2002) Wired for reproduction: organization and development of sexually dimorphic circuits in the mammalian forebrain. Annu Rev Neurosci 25:507–536PubMedCrossRefGoogle Scholar
  39. 39.
    Simerly RB, Chang C, Muramatsu M, Swanson LW (1990) Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: an in situ hybridization study. J Comp Neurol 294:76–95PubMedCrossRefGoogle Scholar
  40. 40.
    Simonian SX, Spratt DP, Herbison AE (1999) Identification and characterization of estrogen receptor alpha-containing neurons projecting to the vicinity of the gonadotropin-releasing hormone perikarya in the rostral preoptic area of the rat. J Comp Neurol 411:346–358PubMedCrossRefGoogle Scholar
  41. 41.
    Soper BD, Weick RF (1980) Hypothalamic and extrahypothalamic mediation of pulsatile discharges of luteinizing hormone in the ovariectomized rat. Endocrinology 106:348–355PubMedCrossRefGoogle Scholar
  42. 42.
    Gu GB, Simerly RB (1997) Projections of the sexually dimorphic anteroventral periventricular nucleus in the female rat. J Comp Neurol 384:142–164PubMedCrossRefGoogle Scholar
  43. 43.
    Herbison AE (2008) Estrogen positive feedback to gonadotropin-releasing hormone (GnRH) neurons in the rodent: the case for the rostral periventricular area of the third ventricle (RP3V). Brain Res Rev 57:277–287PubMedCrossRefGoogle Scholar
  44. 44.
    Simerly RB (1998) Organization and regulation of sexually dimorphic neuroendocrine pathways. Behav Brain Res 92:195–203PubMedCrossRefGoogle Scholar
  45. 45.
    Blache D, Fabre-Nys CJ, Venier G (1991) Ventromedial hypothalamus as a target for oestradiol action on proceptivity, receptivity and luteinizing hormone surge of the ewe. Brain Res 546:241–249PubMedCrossRefGoogle Scholar
  46. 46.
    Caraty A, Fabre-Nys C, Delaleu B, Locatelli A, Bruneau G, Karsch FJ, Herbison A (1998) Evidence that the mediobasal hypothalamus is the primary site of action of estradiol in inducing the preovulatory gonadotropin releasing hormone surge in the ewe. Endocrinology 139:1752–1760PubMedCrossRefGoogle Scholar
  47. 47.
    Cheng G, Coolen LM, Padmanabhan V, Goodman RL, Lehman MN (2010) The kisspeptin/neurokinin B/dynorphin (KNDy) cell population of the arcuate nucleus: sex differences and effects of prenatal testosterone in sheep. Endocrinology 151:301–311PubMedCrossRefGoogle Scholar
  48. 48.
    Hess DL, Wilkins RH, Moossy J, Chang JL, Plant TM, McCormack JT, Nakai Y, Knobil E (1977) Estrogen-induced gonadotropin surges in decerebrated female rhesus monkeys with medial basal hypothalamic peninsulae. Endocrinology 101:1264–1271PubMedCrossRefGoogle Scholar
  49. 49.
    Knobil E, Plant TM, Wildt L, Belchetz PE, Marshall G (1980) Control of the rhesus monkey menstrual cycle: permissive role of hypothalamic gonadotropin-releasing hormone. Science 207:1371–1373PubMedGoogle Scholar
  50. 50.
    Krey LC, Butler WR, Knobil E (1975) Surgical disconnection of the medial basal hypothalamus and pituitary function in the rhesus monkey. I. Gonadotropin secretion. Endocrinology 96:1073–1087PubMedCrossRefGoogle Scholar
  51. 51.
    Norman RL, Resko JA, Spies HG (1976) The anterior hypothalamus: how it affects gonadotropin secretion in the rhesus monkey. Endocrinology 99:59–71PubMedCrossRefGoogle Scholar
  52. 52.
    Cogen P, Antunes JL, Louis KM, Dyrenfurth I, Ferin M (1980) The effects of anterior hypothalamic disconnection on gonadotropin secretion in the female rhesus monkey. Endocrinology 107:677–683PubMedCrossRefGoogle Scholar
  53. 53.
    Smith JT, Cunningham MJ, Rissman EF, Clifton DK, Steiner RA (2005) Regulation of Kiss1 gene expression in the brain of the female mouse. Endocrinology 146:3686–3692PubMedCrossRefGoogle Scholar
  54. 54.
    Navarro VM, Castellano JM, Fernandez-Fernandez R, Barreiro ML, Roa J, Sanchez-Criado JE, Aguilar 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 activity of KiSS-1 peptide. Endocrinology 145:4565–4574PubMedCrossRefGoogle Scholar
  55. 55.
    Shughrue PJ, Lane MV, Merchenthaler I (1997) Regulation of progesterone receptor messenger ribonucleic acid in the rat medial preoptic nucleus by estrogenic and antiestrogenic compounds: an in situ hybridization study. Endocrinology 138:5476–5484PubMedCrossRefGoogle Scholar
  56. 56.
    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 146:2976–2984PubMedCrossRefGoogle Scholar
  57. 57.
    Clarkson J, Shamas S, Mallinson S, Herbison AE (2012) Gonadal steroid induction of kisspeptin peptide expression in the rostral periventricular area of the third ventricle during postnatal development in the male mouse. J Neuroendocrinol 24(6):907–915PubMedCrossRefGoogle Scholar
  58. 58.
    Kim J, Semaan SJ, Clifton DK, Steiner RA, Dhamija S, Kauffman AS (2011) Regulation of Kiss1 expression by sex steroids in the amygdala of the rat and mouse. Endocrinology 152:2020–2030PubMedCrossRefGoogle Scholar
  59. 59.
    Garcia-Galiano D, van Ingen Schenau D, Leon S, Krajnc-Franken MA, Manfredi-Lozano M, Romero-Ruiz A, Navarro VM, Gaytan F, van Noort PI, Pinilla L, Blomenrohr M, Tena-­Sempere M (2012) Kisspeptin signaling is indispensable for neurokinin B, but not glutamate, stimulation of gonadotropin secretion in mice. Endocrinology 153:316–328PubMedCrossRefGoogle Scholar
  60. 60.
    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 29:3920–3929PubMedCrossRefGoogle Scholar
  61. 61.
    Mayer C, Acosta-Martinez M, Dubois SL, Wolfe A, Radovick S, Boehm U, Levine JE (2010) Timing and completion of puberty in female mice depend on estrogen receptor alpha-signaling in kisspeptin neurons. Proc Natl Acad Sci USA 107:22693–22698PubMedCrossRefGoogle Scholar
  62. 62.
    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) Gonadotrophin-releasing hormone pulse generator activity in the hypothalamus of the goat. J Neuroendocrinol 21:813–821PubMedCrossRefGoogle Scholar
  63. 63.
    Goodman RL, Lehman MN, Smith JT, Coolen LM, de Oliveira CV, Jafarzadehshirazi MR, Pereira A, Iqbal J, Caraty A, Ciofi P, Clarke IJ (2007) Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B. Endocrinology 148:5752–5760PubMedCrossRefGoogle Scholar
  64. 64.
    Navarro VM, Gottsch ML, Chavkin C, Okamura H, Clifton DK, Steiner RA (2009) Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse. J Neurosci 29:11859–11866PubMedCrossRefGoogle Scholar
  65. 65.
    Wakabayashi Y, Nakada T, Murata K, Ohkura S, Mogi K, Navarro VM, Clifton DK, Mori Y, Tsukamura H, Maeda K, Steiner RA, Okamura H (2010) Neurokinin B and dynorphin a in kisspeptin neurons of the arcuate nucleus participate in generation of periodic oscillation of neural activity driving pulsatile gonadotropin-releasing hormone secretion in the goat. J Neurosci 30:3124–3132PubMedCrossRefGoogle Scholar
  66. 66.
    Wiegand SJ, Terasawa E, Bridson WE (1978) Persistent estrus and blockade of progesterone-­induced LH release follows lesions which do not damage the suprachiasmatic nucleus. Endocrinology 102:1645–1648PubMedCrossRefGoogle Scholar
  67. 67.
    Clarkson J, d’Anglemont de Tassigny X, Moreno AS, Colledge WH, Herbison AE (2008) Kisspeptin-GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge. J Neurosci 28:8691–8697PubMedCrossRefGoogle Scholar
  68. 68.
    Pineda R, Garcia-Galiano D, Roseweir A, Romero M, Sanchez-Garrido MA, Ruiz-Pino F, Morgan K, Pinilla L, Millar RP, Tena-Sempere M (2010) Critical roles of kisspeptins in female puberty and preovulatory gonadotropin surges as revealed by a novel antagonist. Endocrinology 151:722–730PubMedCrossRefGoogle Scholar
  69. 69.
    Barbacka-Surowiak G, Surowiak J, Stoklosowa S (2003) The involvement of suprachiasmatic nuclei in the regulation of estrous cycles in rodents. Reprod Biol 3:99–129PubMedGoogle Scholar
  70. 70.
    de la Iglesia HO, Schwartz WJ (2006) Minireview: timely ovulation: circadian regulation of the female hypothalamo-pituitary-gonadal axis. Endocrinology 147:1148–1153PubMedCrossRefGoogle Scholar
  71. 71.
    Robertson JL, Clifton DK, de la Iglesia HO, Steiner RA, Kauffman AS (2009) Circadian regulation of Kiss1 neurons: implications for timing the preovulatory gonadotropin-releasing hormone/luteinizing hormone surge. Endocrinology 150:3664–3671PubMedCrossRefGoogle Scholar
  72. 72.
    Williams WP 3rd, Jarjisian SG, Mikkelsen JD, Kriegsfeld LJ (2011) Circadian control of kisspeptin and a gated GnRH response mediate the preovulatory luteinizing hormone surge. Endocrinology 152:595–606PubMedCrossRefGoogle Scholar
  73. 73.
    Smarr BL, Morris E, de la Iglesia HO (2012) The dorsomedial suprachiasmatic nucleus times circadian expression of Kiss1 and the luteinizing hormone surge. Endocrinology 153:2839–2850PubMedCrossRefGoogle Scholar
  74. 74.
    Semaan SJ, Murray EK, Poling MC, Dhamija S, Forger NG, Kauffman AS (2010) BAX-­dependent and BAX-independent regulation of Kiss1 neuron development in mice. Endocrinology 151:5807–5817PubMedCrossRefGoogle Scholar
  75. 75.
    Caraty A, Smith JT, Lomet D, Ben Said 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 148:5258–5267PubMedCrossRefGoogle Scholar
  76. 76.
    Sebert ME, Lomet D, Said 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 38:289–298PubMedCrossRefGoogle Scholar
  77. 77.
    Clarke IJ (1987) GnRH and ovarian hormone feedback. Oxf Rev Reprod Biol 9:54–95PubMedGoogle Scholar
  78. 78.
    Gottsch ML, Navarro VM, Zhao Z, Glidewell-Kenney C, Weiss J, Jameson JL, Clifton DK, Levine JE, Steiner RA (2009) Regulation of Kiss1 and dynorphin gene expression in the murine brain by classical and nonclassical estrogen receptor pathways. J Neurosci 29:9390–9395PubMedCrossRefGoogle Scholar
  79. 79.
    Hoffman GE, Le WW, Franceschini I, Caraty A, Advis JP (2011) Expression of fos and in vivo median eminence release of LHRH identifies an active role for preoptic area kisspeptin neurons in synchronized surges of LH and LHRH in the ewe. Endocrinology 152:214–222PubMedCrossRefGoogle Scholar
  80. 80.
    Tomikawa J, Homma T, Tajima S, Shibata T, Inamoto Y, Takase K, Inoue N, Ohkura S, Uenoyama Y, Maeda K, Tsukamura H (2010) Molecular characterization and estrogen regulation of hypothalamic KISS1 gene in the pig. Biol Reprod 82:313–319PubMedCrossRefGoogle Scholar
  81. 81.
    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 83:568–577PubMedCrossRefGoogle Scholar
  82. 82.
    Porteous R, Petersen SL, Yeo SH, Bhattarai JP, Ciofi P, de Tassigny XD, Colledge WH, Caraty A, Herbison AE (2011) Kisspeptin neurons co-express met-enkephalin and galanin in the rostral periventricular region of the female mouse hypothalamus. J Comp Neurol 519:3456–3469PubMedCrossRefGoogle Scholar
  83. 83.
    Kauffman AS, Navarro VM, Kim J, Clifton D, Steiner RA (2009) Sex differences in the regulation of Kiss1/NKB neurons in Juvenile Mice: implications for the timing of puberty. Am J Physiol Endocrinol Metab 297(5):E1212–E1221PubMedCrossRefGoogle Scholar
  84. 84.
    Li D, Mitchell D, Luo J, Yi Z, Cho SG, Guo J, Li X, Ning G, Wu X, Liu M (2007) Estrogen regulates KiSS1 gene expression through estrogen receptor alpha and SP protein complexes. Endocrinology 148:4821–4828PubMedCrossRefGoogle Scholar
  85. 85.
    Glidewell-Kenney C, Hurley LA, Pfaff L, Weiss J, Levine JE, Jameson JL (2007) Nonclassical estrogen receptor alpha signaling mediates negative feedback in the female mouse reproductive axis. Proc Natl Acad Sci USA 104:8173–8177PubMedCrossRefGoogle Scholar
  86. 86.
    Dhillo WS, Chaudhri OB, Thompson EL, Murphy KG, Patterson M, Ramachandran R, Nijher GK, Amber V, Kokkinos A, Donaldson M, Ghatei MA, Bloom SR (2007) Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women. J Clin Endocrinol Metab 92:3958–3966PubMedCrossRefGoogle Scholar
  87. 87.
    Smith JT, Saleh SN, Clarke IJ (2009) Seasonal and cyclical change in the luteinizing hormone response to kisspeptin in the ewe. Neuroendocrinology 90:283–291PubMedCrossRefGoogle Scholar
  88. 88.
    Roa J, Vigo E, Castellano JM, Navarro VM, Fernandez-Fernandez 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 147:2864–2878PubMedCrossRefGoogle Scholar
  89. 89.
    Roa J, Vigo E, Castellano JM, Gaytan F, Navarro VM, Aguilar E, Dijcks FA, Ederveen AG, Pinilla L, van Noort PI, Tena-Sempere M (2008) Opposite roles of estrogen receptor (ER)-alpha and ERbeta in the modulation of luteinizing hormone responses to kisspeptin in the female rat: implications for the generation of the preovulatory surge. Endocrinology 149:1627–1637PubMedCrossRefGoogle Scholar
  90. 90.
    Roa J, Vigo E, Castellano JM, Gaytan F, Garcia-Galiano D, Navarro VM, Aguilar E, Dijcks FA, Ederveen AG, Pinilla L, van Noort PI, Tena-Sempere M (2008) Follicle-stimulating hormone responses to kisspeptin in the female rat at the preovulatory period: modulation by estrogen and progesterone receptors. Endocrinology 149:5783–5790PubMedCrossRefGoogle Scholar
  91. 91.
    Yamada S, Uenoyama Y, Kinoshita M, Iwata K, Takase K, Matsui H, Adachi S, Inoue K, Maeda KI, Tsukamura H (2007) Inhibition of metastin (Kisspeptin-54)-GPR 54 signaling in the arcuate nucleus-median eminence region during lactation in rats. Endocrinology 148:2226–2232PubMedCrossRefGoogle Scholar
  92. 92.
    Li Q, Roa A, Clarke IJ, Smith JT (2012) Seasonal variation in GnRH response to kisspeptin in sheep: possible kisspeptin regulation of the kisspeptin receptor. Neuroendocrinology 96(3):212–221PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  1. 1.Department of Anatomy, Physiology and Human BiologyThe University of Western AustraliaPerthAustralia

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