Kisspeptin and fertility

Journal of Endocrinology

Volumn 208, Issue 2, 2011, Pages 97-105

  Hameed, Saira ^a   Jayasena, Channa N ^a   Dhillo, Waljit S ^a  

^a HAMMERSMITH HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

FOLLITROPIN; G PROTEIN COUPLED RECEPTOR 54; GONADORELIN; GONADORELIN ANTAGONIST; GONADOTROPIN; KISSPEPTIN; LEPTIN; LEPTIN RECEPTOR; MAMMALIAN TARGET OF RAPAMYCIN; NEUROKININ B; NEUROKININ B AGONIST; NEUROPEPTIDE; RAPAMYCIN; STEROID HORMONE; TACHYKININ RECEPTOR AGONIST; TESTOSTERONE; UNCLASSIFIED DRUG;

AMENORRHEA; CENTRAL NERVOUS SYSTEM; FEEDBACK SYSTEM; FEMALE INFERTILITY; FERTILITY; GONAD; GONADORELIN RELEASE; GONADOTROPIN SECRETING CELL; HORMONAL THERAPY; HUMAN; HYPOGONADOTROPIC HYPOGONADISM; HYPOLEPTINEMIA; HYPOPHYSIS; HYPOTHALAMIC AMENORRHEA; HYPOTHALAMUS; IN VITRO STUDY; IN VIVO STUDY; NERVE CELL; NONHUMAN; NUTRITIONAL STATUS; OVARY HYPERSTIMULATION; POSTMENOPAUSE; PRIORITY JOURNAL; PROTEIN DEFICIENCY; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; PUBERTY; REPRODUCTION; REVIEW; SIGNAL TRANSDUCTION; STEROID RELEASE;

ANIMALS; ARCUATE NUCLEUS; FEEDBACK, PHYSIOLOGICAL; FERTILITY; GONADOTROPIN-RELEASING HORMONE; GONADOTROPINS; GONADS; GROWTH HORMONE; HUMANS; HYPOTHALAMO-HYPOPHYSEAL SYSTEM; HYPOTHALAMUS; INFERTILITY; NEURONS; NEUROPEPTIDES; NUTRITIONAL STATUS; PITUITARY GLAND; PITUITARY-ADRENAL SYSTEM; RECEPTORS, G-PROTEIN-COUPLED; REPRODUCTION; SEASONS; SIGNAL TRANSDUCTION; STEROIDS; TISSUE DISTRIBUTION; TUMOR SUPPRESSOR PROTEINS;

EID: 78951483530     PISSN: 00220795     EISSN: 14796805     Source Type: Journal    
DOI: 10.1677/JOE-10-0265     Document Type: Review

References (91)

1. Ahima RS, Dushay J, Flier SN, Prabakaran D & Flier JS 1997 Leptin accelerates the onset of puberty in normal female mice. Journal of Clinical Investigation 99 391-395. (doi:10.1172/JCI119172) (Pubitemid 27414795)
2. Backholer K, Smith J & 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 5488-5497. (doi:10.1210/en.2009-0604)
3. Backholer K, Smith JT, Rao A, Pereira A, Iqbal J, Ogawa S, Li Q & Clarke IJ 2010 Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells. Endocrinology 151 2233-2243. (doi:10.1210/en.2009-1190)
4. Barry J 1979 Immunohistochemistry of luteinizing hormone-releasing hormone-producing neurons of the vertebrates. International Review of Cytology 60 179-221. (doi:10.1016/S0074-7696(08)61263-2) (Pubitemid 10186407)
5. Bilban M, Ghaffari-Tabrizi N, Hintermann E, Bauer S, Molzer S, Zoratti C, Malli R, Sharabi A, Hiden U, Graier W et al. 2004 Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. Journal of Cell Science 117 1319-1328. (doi:10.1242/jcs.00971)
6. Broberger C, Johansen J, Johansson C, Schalling M & Hokfelt T 1998 The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. PNAS 95 15043-15048. (doi:10.1073/pnas.95.25.15043)
7. Caraty A, Smith JT, Lomet D, Ben SS, 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 5258-5267. (doi:10.1210/en.2007-0554)
8. Castellano JM, Navarro VM, Fernandez-Fernandez R, Nogueiras R, Tovar S, Roa J, Vazquez MJ, Vigo E, Casanueva FF, Aguilar E et al. 2005 Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology 146 3917-3925. (doi:10.1210/en.2005-0337)
9. Chehab FF, Lim ME & Lu R 1996 Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nature Genetics 12 318-320. (doi:10.1038/ng0396-318) (Pubitemid 26080094)
10. Chehab FF, Mounzih K, Lu R & Lim ME 1997 Early onset of reproductive function in normal female mice treated with leptin. Science 275 88-90. (doi:10.1126/science.275.5296.88)
11. Cheung CC, Clifton DK & Steiner RA 1997 Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 138 4489-4492. (doi:10.1210/en.138.10.4489)
12. Clarke IJ, Smith JT, Caraty A, Goodman RL & Lehman MN 2009 Kisspeptin and seasonality in sheep. Peptides 30 154-163. (doi:10.1016/j.peptides.2008.08. 022)
13. Clarkson J & Herbison AE 2006 Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons. Endocrinology 147 5817-5825. (doi:10.1210/en.2006-0787)
14. 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. Journal of Neuroscience 28 8691-8697. (doi:10.1523/JNEUROSCI.1775-08. 2008)
15. Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM et al. 1998 A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392 398-401. (doi:10.1038/32911)
16. Clements MK, McDonald TP, Wang R, Xie G, O'Dowd BF, George SR, Austin CP & Liu Q 2001 FMRFamide-related neuropeptides are agonists of the orphan G-protein-coupled receptor GPR54. Biochemical and Biophysical Research Communications 284 1189-1193. (doi:10.1006/bbrc.2001.5098)
17. Coleman DL 1978 Obese and diabetes: two mutant genes causing diabetes - obesity syndromes in mice. Diabetologia 14 141-148. (doi:10.1007/BF00429772)
18. Cota D, Proulx K, Smith KA, Kozma SC, Thomas G, Woods SC & Seeley RJ 2006 Hypothalamic mTOR signaling regulates food intake. Science 312 927-930. (doi:10.1126/science.1124147)
19. d'Anglemont de Tassigny X, Fagg LA, Dixon JP, Day K, Leitch HG, Hendrick AG, Zahn D, Franceschini I, Caraty A, Carlton MB et al. 2007 Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene. PNAS 104 10714-10719. (doi:10.1073/pnas.0704114104)
20. 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 3926-3932. (doi:10.1210/en.2007-1487)
21. Dhillo WS, Chaudhri OB, Patterson M, Thompson EL, Murphy KG, Badman MK, McGowan BM, Amber V, Patel S, Ghatei MA et al. 2005 Kisspeptin-54 stimulates the hypothalamic-pituitary-gonadal axis in human males. Journal of Clinical Endocrinology and Metabolism 90 6609-6615. (doi:10.1210/jc.2005-1468) (Pubitemid 41759323)
22. Dhillo WS, Savage P, Murphy KG, Chaudhri OB, Patterson M, Nijher GM, Foggo VM, Dancey GS, Mitchell H, Seckl MJ et al. 2006 Plasma kisspeptin is raised in patients with gestational trophoblastic neoplasia and falls during treatment. American Journal of Physiology. Endocrinology and Metabolism 291 E878-E884. (doi:10.1152/ajpendo.00555.2005)
23. Dhillo WS, Chaudhri OB, Thompson EL, Murphy KG, Patterson M, Ramachandran R, Nijher GK, Amber V, Kokkinos A, Donaldson M et al. 2007 Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women. Journal of Clinical Endocrinology and Metabolism 92 3958-3966. (doi:10.1210/jc.2007-1116)
24. 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. Journal of Neuroscience 27 12088-12095. (doi:10.1523/JNEUROSCI.2748- 07.2007)
25. Elchalal U & Schenker JG 1997 The pathophysiology of ovarian hyperstimulation syndrome - views and ideas. Human Reproduction 12 1129-1137. (doi:10.1093/humrep/12.6.1129)
26. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA & O'Rahilly S 1999 Effects of recombinant leptin therapy in a child with congenital leptin deficiency. New England Journal of Medicine 341 879-884. (doi:10.1056/NEJM199909163411204)
27. Gaytan F, Gaytan M, Castellano JM, Romero M, Roa J, Aparicio B, Garrido N, Sanchez-Criado JE, Millar RP, Pellicer A et al. 2009 KiSS-1 in the mammalian ovary: distribution of kisspeptin in human and marmoset and alterations in KiSS-1 mRNA levels in a rat model of ovulatory dysfunction. American Journal of Physiology. Endocrinology and Metabolism 296 E520-E531. (doi:10.1152/ajpendo. 90895.2008)
28. Goodman RL, Coolen LM, Anderson GM, Hardy SL, Valent M, Connors JM, Fitzgerald ME & Lehman MN 2004 Evidence that dynorphin plays a major role in mediating progesterone negative feedback on gonadotropin-releasing hormone neurons in sheep. Endocrinology 145 2959-2967. (doi:10.1210/en.2003-1305) (Pubitemid 38686245)
29. Goodman RL, Lehman MN, Smith JT, Coolen LM, de Oliveira CV, Jafarzadehshirazi MR, Pereira A, Iqbal J, Caraty A, Ciofi P et al. 2007 Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B. Endocrinology 148 5752-5760. (doi:10.1210/en.2007-0961)
30. 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 4073-4077. (doi:10.1210/en.2004-0431)
31. Guran T, Tolhurst G, Bereket A, Rocha N, Porter K, Turan S, Gribble FM, Kotan LD, Akcay T, Atay Z et al. 2009 Hypogonadotropic hypogonadism due to a novel missense mutation in the first extracellular loop of the neurokinin B receptor. Journal of Clinical Endocrinology and Metabolism 94 3633-3639. (doi:10.1210/jc.2009-0551)
32. Gutierrez-Pascual E, Martinez-Fuentes AJ, Pinilla L, Tena-Sempere M, Malagon MM & Castano JP 2007 Direct pituitary effects of kisspeptin: activation of gonadotrophs and somatotrophs and stimulation of luteinising hormone and growth hormone secretion. Journal of Neuroendocrinology 19 521-530. (doi:10.1111/j.1365-2826.2007.01558.x)
33. Horikoshi Y, Matsumoto H, Takatsu Y, Ohtaki T, Kitada C, Usuki S & Fujino M 2003 Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans. Journal of Clinical Endocrinology and Metabolism 88 914-919. (doi:10.1210/jc.2002-021235)
34. Hrabovszky E, Shughrue PJ, Merchenthaler I, Hajszan T, Carpenter CD, Liposits Z & Petersen SL 2000 Detection of estrogen receptor-β messenger ribonucleic acid and 125I-estrogen binding sites in luteinizing hormone-releasing hormone neurons of the rat brain. Endocrinology 141 3506-3509. (doi:10.1210/en.141.9.3506)
35. Hrabovszky E, Ciofi P, Vida B, Horvath MC, Keller E, Caraty A, Bloom SR, Ghatei MA, Dhillo WS, Liposits Z et al. 2010 The kisspeptin system of the human hypothalamus: sexual dimorphism and relationship with gonadotropin-releasing hormone and neurokinin B neurons. European Journal of Neuroscience 31 1984-1998. (doi:10.1111/j.1460-9568.2010.07239.x)
36. 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 80 264-272. (doi:10.1159/000083140)
37. Janneau JL, Maldonado-Estrada J, Tachdjian G, Miran I, Motte N, Saulnier P, Sabourin JC, Cote JF, Simon B, Frydman R et al. 2002 Transcriptional Expression of genes involved in cell invasion and migration by normal and tumoral trophoblast cells. Journal of Clinical Endocrinology and Metabolism 87 5336-5339. (doi:10.1210/jc.2002-021093)
38. Jayasena CN, Nijher GM, Chaudhri OB, Murphy KG, Ranger A, Lim A, Patel D, Mehta A, Todd C, Ramachandran R et al. 2009 Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis. Journal of Clinical Endocrinology and Metabolism 94 4315-4323. (doi:10.1210/jc.2009-0406)
39. Jayasena CN & Dhillo WS 2010 Neurokinin B and Kisspeptin - sexual partners or single agents? Endocrinology 151 4090-4091. (doi:10.1210/en.2010- 0696)
40. Jayasena CN, Nijher GMK, Abbara A, Murphy KG, Lim A, Patel DA, Mehta A, Todd C, Donaldson M, Trew G et al. 2010 Twice-weekly administration of kisspeptin-54 for eight weeks stimulates reproductive hormone release in women with hypothalamic amenorrhea, Endo 2010 meeting, San Diego, CA, USA.
41. Kinoshita M, Tsukamura H, Adachi S, Matsui H, Uenoyama Y, Iwata K, Yamada S, Inoue K, Ohtaki T, Matsumoto H 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. (doi:10.1210/en.2005- 0195) (Pubitemid 41324041)
42. 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 1371-1373. (doi:10.1126/science. 6766566)
43. Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le PE, Brezillon S, Tyldesley R, Suarez-Huerta N, Vandeput F et al. 2001 The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. Journal of Biological Chemistry 276 34631-34636. (doi:10.1074/jbc.M104847200)
44. Krajewski SJ, Anderson MJ, Iles-Shih L, Chen KJ, Urbanski HF & Rance NE 2005 Morphologic evidence that neurokinin B modulates gonadotropin-releasing hormone secretion via neurokinin 3 receptors in the rat median eminence. Journal of Comparative Neurology 489 372-386. (doi:10.1002/cne.20626)
45. Lee JH, Miele ME, Hicks DJ, Phillips KK, Trent JM, Weissman BE & Welch DR 1996 KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. Journal of the National Cancer Institute 88 1731-1737. (doi:10.1093/jnci/88.23.1731)
46. Lee DK, Nguyen T, O'Neill GP, Cheng R, Liu Y, Howard AD, Coulombe N, Tan CP, Tang-Nguyen AT, George SR et al. 1999 Discovery of a receptor related to the galanin receptors. FEBS Letters 446 103-107. (doi:10.1016/S0014-5793(99)00009- 5)
47. Liu X, Lee K & Herbison AE 2008 Kisspeptin excites gonadotropin-releasing hormone neurons through a phospholipase C/calcium-dependent pathway regulating multiple ion channels. Endocrinology 149 4605-4614. (doi:10.1210/en.2008-0321)
48. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S et al. 1995 Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Medicine 1 1155-1161. (doi:10.1038/nm1195-1155)
49. Mead EJ, Maguire JJ, Kuc RE & Davenport AP 2007 Kisspeptins are novel potent vasoconstrictors in humans, with a discrete localization of their receptor, G protein-coupled receptor 54, to atherosclerosis-prone vessels. Endocrinology 148 140-147. (doi:10.1210/en.2006-0818)
50. Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D, Dixon J, Thresher RR, Malinge I, Lomet D, Carlton MB et al. 2005 Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. PNAS 102 1761-1766. (doi:10.1073/pnas.0409330102) (Pubitemid 40209241)
51. Muir AI, Chamberlain L, Elshourbagy NA, Michalovich D, Moore DJ, Calamari A, Szekeres PG, Sarau HM, Chambers JK, Murdock P et al. 2001 AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. Journal of Biological Chemistry 276 28969-28975. (doi:10.1074/jbc.M102743200)
52. National Institute for Health and Clinical Excellence 2004 Fertility Assessment and Treatment for People with Fertility Problems. http://www.nice.org.uk/nicemedia/live/10936/29269/29269.pdf.
53. Navarro VM, Fernandez-Fernandez R, Castellano JM, Roa J, Mayen A, Barreiro ML, Gaytan F, Aguilar E, Pinilla L, Dieguez C et al. 2004 Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54. Journal of Physiology 561 379-386. (doi:10.1113/jphysiol.2004.072298) (Pubitemid 39646528)
54. Navarro VM, Castellano JM, Fernandez-Fernandez R, Tovar S, Roa J, Mayen A, Nogueiras R, Vazquez MJ, Barreiro ML, Magni P et al. 2005 Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54. Endocrinology 146 156-163. (doi:10.1210/en.2004-0836)
55. 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. Journal of Neuroscience 29 11859-11866. (doi:10.1523/JNEUROSCI.1569-09.2009)
56. Nijher G, Chaudhri O, Ramachandran R, Murphy K, Zac-Varghese S, Fowler A, Chinthapalli K, Patterson M, Thompson E, Williamson C et al. 2010 The effects of kisspeptin-54 on blood pressure in humans and plasma kisspeptin levels in hypertensive diseases of pregnancy. British Journal of Clinical Pharmacology 70 674-681. (doi:10.1111/j.1365-2125.2010.03746.x)
57. Novaira HJ, Ng Y, Wolfe A & Radovick S 2009 Kisspeptin increases GnRH mRNA expression and secretion in GnRH secreting neuronal cell lines. Molecular and Cellular Endocrinology 311 126-134. (doi:10.1016/j.mce.2009.06.011)
58. Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K, Terao Y, Kumano S, Takatsu Y, Masuda Y et al. 2001 Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 411 613-617. (doi:10.1038/35079135)
59. Pallais JC, Bo-Abbas Y, Pitteloud N, Crowley WF Jr & Seminara SB 2006 Neuroendocrine, gonadal, placental, and obstetric phenotypes in patients with IHH and mutations in the G-protein coupled receptor, GPR54. Molecular and Cellular Endocrinology 254-255 70-77. (doi:10.1016/j.mce.2006.04.019) (Pubitemid 44041755)
60. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T & Collins F 1995 Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269 540-543. (doi:10.1126/science.7624776)
61. 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 151 722-730. (doi:10.1210/en.2009- 0803)
62. Plant TM, Ramaswamy S & Dipietro MJ 2006 Repetitive activation of hypothalamic G protein-coupled receptor 54 with intravenous pulses of kisspeptin in the juvenile monkey (Macaca mulatta) elicits a sustained train of gonadotropin-releasing hormone discharges. Endocrinology 147 1007-1013. (doi:10.1210/en.2005-1261)
63. Ramaswamy S, Seminara SB, Ali B, Ciofi P, Amin NA & Plant TM 2010 Neurokinin B stimulates GnRH release in the male monkey (Macaca mulatta) and is colocalized with kisspeptin in the arcuate nucleus. Endocrinology 151 4494-4503. (doi:10.1210/en.2010-0223)
64. Rance NE 2009 Menopause and the human hypothalamus: evidence for the role of kisspeptin/neurokinin B neurons in the regulation of estrogen negative feedback. Peptides 30 111-122. (doi:10.1016/j.peptides.2008.05.016)
65. Rance NE, Young WS III & McMullen NT 1994 Topography of neurons expressing luteinizing hormone-releasing hormone gene transcripts in the human hypothalamus and basal forebrain. Journal of Comparative Neurology 339 573-586. (doi:10.1002/cne.903390408)
66. Revel FG, Saboureau M, Masson-Pévet M, Pévet P, Mikkelsen JD & Simonneaux V 2006 Kisspeptin mediates the photoperiodic control of reproduction in hamsters. Current Biology 16 1730-1735. (doi:10.1016/j.cub.2006. 07.025)
67. Revel FG, Ansel L, Klosen P, Saboureau M, Pévet P, Mikkelsen JD & Simonneaux V 2007 Kisspeptin: a key link to seasonal breeding. Reviews in Endocrine and Metabolic Disorders 8 57-65. (doi:10.1007/s11154-007-9031-7)
68. Richard N, Galmiche G, Corvaisier S, Caraty A & Kottler ML 2008 KiSS-1 and GPR54 genes are co-expressed in rat gonadotrophs and differentially regulated in vivo by oestradiol and gonadotrophin-releasing hormone. Journal of Neuroendocrinology 20 381-393. (doi:10.1111/j.1365-2826.2008.01653.x)
69. 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 2864-2878. (doi:10.1210/en.2005-1463)
70. Roa J, Vigo E, Castellano JM, Gaytan F, Navarro VM, Aguilar E, Dijcks FA, Ederveen AG, Pinilla L, van Noort PI et al. 2008 Opposite roles of estrogen receptor (ER)-α and ERβ in the modulation of luteinizing hormone responses to kisspeptin in the female rat: implications for the generation of the preovulatory surge. Endocrinology 149 1627-1637. (doi:10.1210/en.2007-1540) (Pubitemid 351468345)
71. Roa J, Garcia-Galiano D, Varela L, Sanchez-Garrido MA, Pineda R, Castellano JM, Ruiz-Pino F, Romero M, Aguilar E, Lopez M et al. 2009 The mammalian target of rapamycin as novel central regulator of puberty onset via modulation of hypothalamic Kiss1 system. Endocrinology 150 5016-5026. (doi:10.1210/en.2009-0096)
72. 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. Journal of Clinical Endocrinology and Metabolism 92 2744-2750. (doi:10.1210/jc.2007-0553)
73. Roseweir AK, Kauffman AS, Smith JT, Guerriero KA, Morgan K, Pielecka-Fortuna J, Pineda R, Gottsch ML, Tena-Sempere M, Moenter SM et al. 2009 Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation. Journal of Neuroscience 29 3920-3929. (doi:10.1523/JNEUROSCI.5740-08.2009)
74. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL & Milgrom E 2003 Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. PNAS 100 10972-10976. (doi:10.1073/pnas.1834399100)
75. Schmelzle T & Hall MN 2000 TOR, a central controller of cell growth. Cell 103 253-262.
76. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG et al. 2003 The GPR54 gene as a regulator of puberty. New England Journal of Medicine 349 1614-1627. (doi:10.1056/NEJMoa035322)
77. Seminara SB, Dipietro MJ, Ramaswamy S, Crowley WF Jr & Plant TM 2006 Continuous human metastin 45-54 infusion desensitizes G protein-coupled receptor 54-induced gonadotropin-releasing hormone release monitored indirectly in the juvenile male Rhesus monkey (Macaca mulatta): a finding with therapeutic implications. Endocrinology 147 2122-2126. (doi:10.1210/en.2005-1550)
78. 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. PNAS 102 2129-2134. (doi:10.1073/pnas. 0409822102)
79. Silverman AJ, Antunes JL, Ferin M & Zimmerman EA 1977 The distribution of luteinizing hormone-releasing hormone (LHRH) in the hypothalamus of the rhesus monkey. Light microscopic studies using immunoperoxidase technique. Endocrinology 101 134-142. (doi:10.1210/endo-101-1-134)
80. 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 3686-3692. (doi:10.1210/en.2005-0488)
81. Smith JT, Acohido BV, Clifton DK & Steiner RA 2006a KiSS-1 neurones are direct targets for leptin in the ob/ob mouse. Journal of Neuroendocrinology 18 298-303. (doi:10.1111/j.1365-2826.2006.01417.x)
82. Smith JT, Popa SM, Clifton DK, Hoffman GE & Steiner RA 2006b Kiss1 neurons in the forebrain as central processors for generating the preovulatory luteinizing hormone surge. Journal of Neuroscience 26 6687-6694. (doi:10.1523/JNEUROSCI.1618-06.2006)
83. Smith JT, Rao A, Pereira A, Caraty A, Millar RP & Clarke IJ 2008 Kisspeptin is present in ovine hypophysial portal 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. (doi:10.1210/en.2007-1425) (Pubitemid 351468347)
84. Teles MG, Bianco SD, Brito VN, Trarbach EB, Kuohung W, Xu S, Seminara SB, Mendonca BB, Kaiser UB & Latronico AC 2008 A GPR54-activating mutation in a patient with central precocious puberty. New England Journal of Medicine 358 709-715. (doi:10.1056/NEJMoa073443)
85. Thompson EL, Patterson M, Murphy KG, Smith KL, Dhillo WS, Todd JF, Ghatei MA & Bloom SR 2004 Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. Journal of Neuroendocrinology 16 850-858. (doi:10.1111/j.1365-2826.2004.01240.x) (Pubitemid 39489998)
86. Todman MG, Han SK & Herbison AE 2005 Profiling neurotransmitter receptor expression in mouse gonadotropin-releasing hormone neurons using green fluorescent protein-promoter transgenics and microarrays. Neuroscience 132 703-712. (doi:10.1016/j.neuroscience.2005.01.035)
87. Topaloglu AK, Reimann F, Guclu M, Yalin AS, Kotan LD, Porter KM, Serin A, Mungan NO, Cook JR, Ozbek MN et al. 2009 TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for neurokinin B in the central control of reproduction. Nature Genetics 41 354-358. (doi:10.1038/ng.306)
88. Welt CK, Chan JL, Bullen J, Murphy R, Smith P, DePaoli AM, Karalis A & Mantzoros CS 2004 Recombinant human leptin in women with hypothalamic amenorrhea. New England Journal of Medicine 351 987-997. (doi:10.1056/ NEJMoa040388)
89. Wintermantel TM, Campbell RE, Porteous R, Bock D, Grone HJ, Todman MG, Korach KS, Greiner E, Perez CA, Schutz G et al. 2006 Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin- releasing hormone neurons and fertility. Neuron 52 271-280. (doi:10.1016/j. neuron.2006.07.023)
90. Wu M, Dumalska I, Morozova E, van den PA & Alreja M 2009 Melanin-concentrating hormone directly inhibits GnRH neurons and blocks kisspeptin activation, linking energy balance to reproduction. PNAS 106 17217-17222. (doi:10.1073/pnas.0908200106)
91. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L & Friedman JM 1994 Positional cloning of the mouse obese gene and its human homologue. Nature 372 425-432. (doi:10.1038/372425a0) (Pubitemid 24365442)