Kisspeptins in reproductive biology: Consensus knowledge and recent developments

Biology of Reproduction

Volumn 85, Issue 4, 2011, Pages 650-660

  Roa, Juan ^a,d   Navarro, Victor M ^a,e   Tena Sempere, Manuel ^a,b,c  

^a UNIVERSITY OF CÓRDOBA   (Spain)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

^c Hospital Universitario Reina Sofia   (Spain)

^d UNIVERSITY OF OTAGO   (New Zealand)

^e UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Gonadotropin releasing hormone (GnRH GnRH receptor); Gonadotropins; GPR54; Kiss1; Kiss1R; Kisspeptin; Leptin; Neuroendocrinology; Ovulation; Puberty; Reproduction; Sex steroids

Indexed keywords

ALPHA INTERMEDIN; DYNORPHIN; GONADORELIN; GONADOTROPIN; KISSPEPTIN; KISSPEPTIN 1; LEPTIN; LUTEINIZING HORMONE; NEUROKININ B; PROOPIOMELANOCORTIN; SEX HORMONE; UNCLASSIFIED DRUG;

ANTEROVENTRAL PERIVENTRICULAR AREA; ARCUATE NUCLEUS; BRAIN NERVE CELL; BRAIN REGION; CELL POPULATION; ENERGY BALANCE; ENVIRONMENTAL FACTOR; FERTILITY; GONADORELIN RELEASE; GONADOTROPIN RELEASE; HUMAN; HYPOTHALAMUS; LUTEINIZING HORMONE RELEASE; METABOLIC REGULATION; NEGATIVE FEEDBACK; NEUROANATOMY; NONHUMAN; OVULATION; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PUBERTY; REPRODUCTION; SENSORY NERVE; SEX DIFFERENTIATION; SHORT SURVEY;

ANIMALS; ARCUATE NUCLEUS; ENERGY METABOLISM; FEEDBACK, PHYSIOLOGICAL; FEMALE; GONADAL STEROID HORMONES; GONADOTROPIN-RELEASING HORMONE; HUMANS; KISSPEPTINS; LEPTIN; MALE; NEURONS; NEUROPEPTIDES; OVULATION; PROTEIN ISOFORMS; REPRODUCTION; SEXUAL DEVELOPMENT; SYNAPTIC TRANSMISSION; THALAMIC NUCLEI;

EID: 80955123891     PISSN: 00063363     EISSN: 15297268     Source Type: Journal    
DOI: 10.1095/biolreprod.111.091538     Document Type: Short Survey

References (108)

1. Roa J, Aguilar E, Dieguez C, Pinilla L, Tena-Sempere M. New frontiers in kisspeptin/GPR54 physiology as fundamental gatekeepers of repro- ductive function. Front Neuroendocrinol 2008; 29:48-69.
2. Fink G. Neuroendocrine regulation of pituitary function: general principles. In: Conn PM, Freeman ME (eds.), Neuroendocrinology in Physiology and Medicine. Totowa, New Jersey: Humana Press; 2000:107-134.
3. Tena-Sempere M, Huhtaniemi I. Gonadotropins and gonadotropin receptors. In: Fauser BCJM (ed.), Reproductive Medicine-Molecular, Cellular and Genetic Fundamentals. New York: Parthenon Publishing; 2003:225-244.
4. Tena-Sempere M. GPR54 and kisspeptin in reproduction. Hum Reprod Update 2006; 12:631-639.
5. Tena-Sempere M. Timeline: the role of kisspeptins in reproductive biology. Nat Med 2008; 14:1196.
6. Oakley AE, Clifton DK, Steiner RA. Kisspeptin signaling in the brain. Endocr Rev 2009; 30:713-743.
7. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG, Zahn D, Dixon J, et al. The GPR54 gene as a regulator of puberty. N Engl J Med 2003; 349:1614-1627.
8. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1- derived peptide receptor GPR54. Proc Natl Acad Sci U S A 2003; 100:10972-10976.
9. d'Anglemont de Tassigny X, Fagg LA, Dixon JP, Day K, Leitch HG, Hendrick AG, Zahn D, Franceschini I, Caraty A, Carlton MB, Aparicio SA, Colledge WH. Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene. Proc Natl Acad Sci U S A 2007; 104:10714- 10719.
10. Tena-Sempere M. Roles of kisspeptins in the control of hypothalamic- gonadotropic function: focus on sexual differentiation and puberty onset. Endocr Dev 2010; 17:52-62.
11. Roa J, Garcia-Galiano D, Castellano JM, Gaytan F, Pinilla L, Tena- Sempere M. Metabolic control of puberty onset: new players, new mechanisms. Mol Cell Endocrinol 2010; 324:87-94.
12. Castellano JM, Bentsen AH, Mikkelsen JD, Tena-Sempere M. Kisspeptins: bridging energy homeostasis and reproduction. Brain Res 2010; 1364:129-138.
13. Gottsch ML, Clifton DK, Steiner RA. From KISS1 to kisspeptins: an historical perspective and suggested nomenclature. Peptides 2009; 30:4-9.
14. Smith JT, Dungan HM, Stoll EA, Gottsch ML, Braun RE, Eacker SM, Clifton DK, Steiner RA. Differential regulation of KiSS-1 mRNA expression by sex steroids in the brain of the male mouse. Endocrinology 2005; 146:2976-2984.
15. Smith JT, Cunningham MJ, Rissman EF, Clifton DK, Steiner RA. Regulation of Kiss1 gene expression in the brain of the female mouse. Endocrinology 2005; 146:3686-3692.
16. Clarkson J, Herbison AE. Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotro- pin-releasing hormone neurons. Endocrinology 2006; 147:5817-5825.
17. Herbison AE. 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 2008; 57:277-287.
18. Gottsch ML, Cunningham MJ, Smith JT, Popa SM, Acohido BV, Crowley WF, Seminara S, Clifton DK, Steiner RA. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 2004; 145:4073-4077.
19. Kim J, Semaan SJ, Clifton DK, Steiner RA, Dhamija S, Kauffman AS. Regulation of kiss1 expression by sex steroids in the amygdala of the rat and mouse. Endocrinology 2011; 152:2020-2030.
20. Mikkelsen JD, Simonneaux V. The neuroanatomy of the kisspeptin system in the mammalian brain. Peptides 2009; 30:26-33.
21. Dun SL, Brailoiu GC, Parsons A, Yang J, Zeng Q, Chen X, Chang JK, Dun NJ. Metastin-like immunoreactivity in the rat medulla oblongata and spinal cord. Neurosci Lett 2003; 335:197-201.
22. Brailoiu GC, Dun SL, Ohsawa M, Yin D, Yang J, Chang JK, Brailoiu E, Dun NJ. KiSS-1 expression and metastin-like immunoreactivity in the rat brain. J Comp Neurol 2005; 481:314-329.
23. Cravo RM, Margatho LO, Osborne-Lawrence S, Donato J Jr, Atkin S, Bookout AL, Rovinsky S, Frazao R, Lee CE, Gautron L, Zigman JM, Elias CF. Characterization of Kiss1 neurons using transgenic mouse models. Neuroscience 2011; 173:37-56.
24. Clarkson J, d'Anglemont de Tassigny X, Colledge WH, Caraty A, Herbison AE. Distribution of kisspeptin neurones in the adult female mouse brain. J Neuroendocrinol 2009; 21:673-682.
25. Yeo SH, Herbison AE. Projections of arcuate nucleus and rostral periventricular kisspeptin neurons in the adult female mouse brain. Endocrinology 2011; 152:2387-2399.
26. Smith JT, Li Q, Yap KS, Shahab M, Roseweir AK, Millar RP, Clarke IJ. Kisspeptin is essential for the full preovulatory LH surge and stimulates GnRH release from the isolated ovine median eminence. Endocrinology 2011; 152:1001-1012.
27. Ramaswamy S, Guerriero KA, Gibbs RB, Plant TM. 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 2008; 149:4387-4395.
28. Herbison AE, d'Anglemont de Tassigny X, Doran J, Colledge WH. Distribution and postnatal development of Gpr54 gene expression in mouse brain and gonadotropin-releasing hormone neurons. Endocrinology 2010; 151:312-321.
29. Kauffman AS, Gottsch ML, Roa J, Byquist AC, Crown A, Clifton DK, Hoffman GE, Steiner RA, Tena-Sempere M. Sexual differentiation of Kiss1 gene expression in the brain of the rat. Endocrinology 2007; 148:1774-1783.
30. Takase K, Uenoyama Y, Inoue N, Matsui H, Yamada S, Shimizu M, Homma T, Tomikawa J, Kanda S, Matsumoto H, Oka Y, Tsukamura H, Maeda KI. Possible role of oestrogen in pubertal increase of Kiss1/kisspeptin expression in discrete hypothalamic areas of female rats. J Neuroendocrinol 2009; 21:527-537.
31. Morris JA, Jordan CL, Breedlove SM. Sexual differentiation of the vertebrate nervous system. Nat Neurosci 2004; 7:1034-1039.
32. Homma T, Sakakibara M, Yamada S, Kinoshita M, Iwata K, Tomikawa J, Kanazawa T, Matsui H, Takatsu Y, Ohtaki T, Matsumoto H, Uenoyama Y, et al. Significance of neonatal testicular sex steroids to defeminize anteroventral periventricular kisspeptin neurons and the GnRH/LH surge system in male rats. Biol Reprod 2009; 81:1216-1225.
33. Gill JC, Wang O, Kakar S, Martinelli E, Carroll RS, Kaiser UB. Reproductive hormone-dependent and -independent contributions to developmental changes in kisspeptin in GnRH-deficient hypogonadal mice. PLoS One 2010; 5:e11911.
34. Bakker J, Pierman S, Gonzalez-Martinez D. Effects of aromatase mutation (ArKO) on the sexual differentiation of kisspeptin neuronal numbers and their activation by same versus opposite sex urinary pheromones. Horm Behav 2010; 57:390-395.
35. Navarro VM, Sanchez-Garrido MA, Castellano JM, Roa J, Garcia- Galiano D, Pineda R, Aguilar E, Pinilla L, Tena-Sempere M. Persistent impairment of hypothalamic KiSS-1 system after exposures to estrogenic compounds at critical periods of brain sex differentiation. Endocrinology 2009; 150:2359-2367.
36. Iijima N, Takumi K, Sawai N, Ozawa H. An immunohistochemical study on the expressional dynamics of kisspeptin neurons relevant to GnRH neurons using a newly developed anti-kisspeptin antibody. J Mol Neurosci 2011; 43:146-154.
37. Cheng G, Coolen LM, Padmanabhan V, Goodman RL, Lehman MN. The kisspeptin/neurokinin B/dynorphin (KNDy) cell population of the arcuate nucleus: sex differences and effects of prenatal testosterone in sheep. Endocrinology 2010; 151:301-311.
38. Hrabovszky E, Ciofi P, Vida B, Horvath MC, Keller E, Caraty A, Bloom SR, Ghatei MA, Dhillo WS, Liposits Z, Kallo I. The kisspeptin system of the human hypothalamus: sexual dimorphism and relationship with gonadotropin-releasing hormone and neurokinin B neurons. Eur J Neurosci 2010; 31:1984-1998.
39. Semaan SJ, Murray EK, Poling MC, Dhamija S, Forger NG, Kauffman AS. BAX-dependent and BAX-independent regulation of Kiss1 neuron development in mice. Endocrinology 2010; 151:5807-5817.
40. Pineda R, Garcia-Galiano D, Roseweir A, Romero M, Sanchez-Garrido MA, Ruiz-Pino F, Morgan K, Pinilla L, Millar RP, Tena-Sempere M. Critical roles of kisspeptins in female puberty and preovulatory gonadotropin surges as revealed by a novel antagonist. Endocrinology 2010; 151:722-730.
41. Navarro VM, Fernandez-Fernandez R, Castellano JM, Roa J, Mayen A, Barreiro ML, Gaytan F, Aguilar E, Pinilla L, Dieguez C, Tena-Sempere M. Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54. J Physiol 2004; 561:379-386.
42. Navarro VM, Castellano JM, Fernandez-Fernandez R, Barreiro ML, Roa J, Sanchez-Criado JE, Aguilar E, Dieguez C, Pinilla L, Tena-Sempere M. 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 2004; 145:4565-4574.
43. Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM. Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci U S A 2005; 102:2129-2134.
44. Han SK, Gottsch ML, Lee KJ, Popa SM, Smith JT, Jakawich SK, Clifton DK, Steiner RA, Herbison AE. Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. J Neurosci 2005; 25:11349-11356.
45. 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 hormone system of the rat. Mol Cell Endocrinol 2006; 257-258:75-83.
46. Roa J, Vigo E, Garcia-Galiano D, Castellano JM, Navarro VM, Pineda R, Dieguez C, Aguilar E, Pinilla L, Tena-Sempere M. Desensitization of gonadotropin responses to kisspeptin in the female rat: analyses of LH and FSH secretion at different developmental and metabolic states. Am J Physiol Endocrinol Metab 2008; 294:E1088- E1096.
47. Clarkson J, Boon WC, Simpson ER, Herbison AE. Postnatal development of an estradiol-kisspeptin positive feedback mechanism implicated in puberty onset. Endocrinology 2009; 150:3214-3220.
48. Mayer C, Acosta-Martinez M, Dubois SL, Wolfe A, Radovick S, Boehm U, Levine JE. Timing and completion of puberty in female mice depend on estrogen receptor alpha-signaling in kisspeptin neurons. Proc Natl Acad Sci U S A 2010; 107:22693-22698.
49. Roa J, Castellano JM, Navarro VM, Handelsman DJ, Pinilla L, Tena- Sempere M. Kisspeptins and the control of gonadotropin secretion in male and female rodents. Peptides 2009; 30:57-66.
50. d'Anglemont de Tassigny X, Fagg LA, Carlton MB, Colledge WH. Kisspeptin can stimulate gonadotropin-releasing hormone (GnRH) release by a direct action at GnRH nerve terminals. Endocrinology 2008; 149:3926-3932.
51. Pielecka-Fortuna J, Moenter SM. Kisspeptin increases gamma-amino- butyric acidergic and glutamatergic transmission directly to gonadotro- pin-releasing hormone neurons in an estradiol-dependent manner. Endocrinology 2010; 151:291-300.
52. Smith JT, Coolen LM, Kriegsfeld LJ, Sari IP, Jaafarzadehshirazi MR, Maltby M, Bateman K, Goodman RL, Tilbrook AJ, Ubuka T, Bentley GE, Clarke IJ, Lehman MN. 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 2008; 149:5770-5782.
53. Topaloglu AK, Reimann F, Guclu M, Yalin AS, Kotan LD, Porter KM, Serin A, Mungan NO, Cook JR, Ozbek MN, Imamoglu S, Akalin NS, et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for neurokinin B in the central control of reproduction. Nat Genet 2009; 41:354-358.
54. Li XF, Kinsey-Jones JS, Cheng Y, Knox AM, Lin Y, Petrou NA, Roseweir A, Lightman SL, Milligan SR, Millar RP, O'Byrne KT. Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat. PLoS One 2009; 4:e8334.
55. Wakabayashi Y, Nakada T, Murata K, Ohkura S, Mogi K, Navarro VM, Clifton DK, Mori Y, Tsukamura H, Maeda K, Steiner RA, Okamura H. 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 2010; 30:3124-3132.
56. Gutierrez-Pascual E, Martinez-Fuentes AJ, Pinilla L, Tena-Sempere M, Malagon MM, Castano JP. Direct pituitary effects of kisspeptin: activation of gonadotrophs and somatotrophs and stimulation of luteinising hormone and growth hormone secretion. J Neuroendocrinol 2007; 19:521-530.
57. Smith JT, Rao A, Pereira A, Caraty A, Millar RP, Clarke IJ. 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 2008; 149:1951-1959.
58. Luque RM, Cordoba-Chacon J, Gahete MD, Navarro VM, Tena- Sempere M, Kineman RD, Castano JP. Kisspeptin regulates gonadotroph and somatotroph function in nonhuman primate pituitary via common and distinct signaling mechanisms. Endocrinology 2011; 152:957-966.
59. Richard N, Galmiche G, Corvaisier S, Caraty A, Kottler ML. KiSS-1 and GPR54 genes are co-expressed in rat gonadotrophs and differentially regulated in vivo by oestradiol and gonadotrophin-releasing hormone. J Neuroendocrinol 2008; 20:381-393.
60. Christian CA, Moenter SM. The neurobiology of preovulatory and estradiol-induced gonadotropin-releasing hormone surges. Endocr Rev 2010; 31:544-577.
61. Wintermantel TM, Campbell RE, Porteous R, Bock D, Grone HJ, Todman MG, Korach KS, Greiner E, Perez CA, Schutz G, Herbison AE. Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility. Neuron 2006; 52:271-280.
62. Clarkson J, d'Anglemont de Tassigny X, Moreno AS, Colledge WH, Herbison AE. Kisspeptin-GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge. J Neurosci 2008; 28:8691-8697.
63. Kinoshita M, Tsukamura H, Adachi S, Matsui H, Uenoyama Y, Iwata K, Yamada S, Inoue K, Ohtaki T, Matsumoto H, Maeda K. Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats. Endocrinology 2005; 146:4431-4436.
64. Dungan HM, Gottsch ML, Zeng H, Gragerov A, Bergmann JE, Vassilatis DK, Clifton DK, Steiner RA. The role of kisspeptin-GPR54 signaling in the tonic regulation and surge release of gonadotropin-releasing hormone/luteinizing hormone. J Neurosci 2007; 27:12088-12095.
65. Gottsch ML, Navarro VM, Zhao Z, Glidewell-Kenney C, Weiss J, Jameson JL, Clifton DK, Levine JE, Steiner RA. Regulation of Kiss1 and dynorphin gene expression in the murine brain by classical and nonclassical estrogen receptor pathways. J Neurosci 2009; 29:9390- 9395.
66. Estrada KM, Clay CM, Pompolo S, Smith JT, Clarke IJ. Elevated KiSS-1 expression in the arcuate nucleus prior to the cyclic preovulatory gonadotrophin-releasing hormone/lutenising hormone surge in the ewe suggests a stimulatory role for kisspeptin in oestrogen-positive feedback. J Neuroendocrinol 2006; 18:806-809.
67. Smith JT, Li Q, Pereira A, Clarke IJ. Kisspeptin neurons in the ovine arcuate nucleus and preoptic area are involved in the preovulatory luteinizing hormone surge. Endocrinology 2009; 150:5530-5538.
68. Navarro VM, Gottsch ML, Chavkin C, Okamura H, Clifton DK, Steiner RA. Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse. J Neurosci 2009; 29:11859-11866.
69. Goodman RL, Lehman MN, Smith JT, Coolen LM, de Oliveira CV, Jafarzadehshirazi MR, Pereira A, Iqbal J, Caraty A, Ciofi P, Clarke IJ. Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B. Endocrinology 2007; 148:5752-5760.
70. Roa J, Vigo E, Castellano JM, Gaytan F, Navarro VM, Aguilar E, Dijcks FA, Ederveen AG, Pinilla L, van Noort PI, Tena-Sempere M. 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 2008; 149:1627-1637.
71. 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. Follicle-stimulating hormone responses to kisspeptin in the female rat at the preovulatory period: modulation by estrogen and progesterone receptors. Endocrinology 2008; 149:5783-5790.
72. Liu X, Lee K, Herbison AE. Kisspeptin excites gonadotropin-releasing hormone neurons through a phospholipase C/calcium-dependent pathway regulating multiple ion channels. Endocrinology 2008; 149:4605-4614.
73. Zhang C, Roepke TA, Kelly MJ, Ronnekleiv OK. Kisspeptin depolarizes gonadotropin-releasing hormone neurons through activation of TRPC- like cationic channels. J Neurosci 2008; 28:4423-4434.
74. Constantin S, Caligioni CS, Stojilkovic S, Wray S. Kisspeptin-10 facilitates a plasma membrane-driven calcium oscillator in gonadotropin- releasing hormone-1 neurons. Endocrinology 2009; 150:1400-1412.
75. Castano JP, Martinez-Fuentes AJ, Gutierrez-Pascual E, Vaudry H, Tena- Sempere M, Malagon MM. Intracellular signaling pathways activated by kisspeptins through GPR54: do multiple signals underlie function diversity? Peptides 2009; 30:10-15.
76. Pampillo M, Camuso N, Taylor JE, Szereszewski JM, Ahow MR, Zajac M, Millar RP, Bhattacharya M, Babwah AV. Regulation of GPR54 signaling by GRK2 and beta-arrestin. Mol Endocrinol 2009; 23:2060- 2074.
77. Lehman MN, Coolen LM, Goodman RL. Minireview: kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone secretion. Endocrinology 2010; 151:3479-3489.
78. Corander MP, Challis BG, Thompson EL, Jovanovic Z, Loraine Tung YC, Rimmington D, Huhtaniemi IT, Murphy KG, Topaloglu AK, Yeo GS, O'Rahilly S, Dhillo WS, et al. The effects of neurokinin B upon gonadotrophin release in male rodents. J Neuroendocrinol 2010; 22:181- 187.
79. Regoli D, Nguyen QT, Jukic D. Neurokinin receptor subtypes characterized by biological assays. Life Sci 1994; 54:2035-2047.
80. Siuciak JA, McCarthy SA, Martin AN, Chapin DS, Stock J, Nadeau DM, Kantesaria S, Bryce-Pritt D, McLean S. Disruption of the neurokinin-3 receptor (NK3) in mice leads to cognitive deficits. Psychopharmacology (Berl) 2007; 194:185-195.
81. Billings HJ, Connors JM, Altman SN, Hileman SM, Holaskova I, Lehman MN, McManus CJ, Nestor CC, Jacobs BH, Goodman RL. Neurokinin B acts via the neurokinin-3 receptor in the retrochiasmatic area to stimulate luteinizing hormone secretion in sheep. Endocrinology 2010; 151:3836-3846.
82. Ramaswamy S, Seminara SB, Ali B, Ciofi P, Amin NA, Plant TM. Neurokinin B stimulates GnRH release in the male monkey (Macaca mulatta) and is colocalized with kisspeptin in the arcuate nucleus. Endocrinology 2010; 151:4494-4503.
83. Navarro VM, Castellano JM, McConkey SM, Pineda R, Ruiz-Pino F, Pinilla L, Clifton DK, Tena-Sempere M, Steiner RA. Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat. Am J Physiol Endocrinol Metab 2011; 300:E202-E210.
84. Rance NE, Krajewski SJ, Smith MA, Cholanian M, Dacks PA. Neurokinin B and the hypothalamic regulation of reproduction. Brain Res 2010; 1364:116-128.
85. True C, Kirigiti M, Ciofi P, Grove KL, Smith MS. Characterisation of arcuate nucleus kisspeptin/neurokinin B neuronal projections and regulation during lactation in the rat. J Neuroendocrinol 2011; 23:52-64.
86. Fernandez-Fernandez R, Martini AC, Navarro VM, Castellano JM, Dieguez C, Aguilar E, Pinilla L, Tena-Sempere M. Novel signals for the integration of energy balance and reproduction. Mol Cell Endocrinol 2006; 254-255:127-132.
87. Tena-Sempere M. Ghrelin as a pleotrophic modulator of gonadal function and reproduction. Nat Clin Pract Endocrinol Metab 2008; 4:666-674.
88. Quennell JH, Mulligan AC, Tups A, Liu X, Phipps SJ, Kemp CJ, Herbison AE, Grattan DR, Anderson GM. Leptin indirectly regulates gonadotropin-releasing hormone neuronal function. Endocrinology 2009; 150:2805-2812.
89. Sexton WJ, Jarow JP. Effect of diabetes mellitus upon male reproductive function. Urology 1997; 49:508-513.
90. Wade GN, Jones JE. Neuroendocrinology of nutritional infertility. Am J Physiol Regul Integr Comp Physiol 2004; 287:R1277-R1296.
91. Luque RM, Kineman RD, Tena-Sempere M. Regulation of hypothalamic expression of KiSS-1 and GPR54 genes by metabolic factors: analyses using mouse models and a cell line. Endocrinology 2007; 148:4601- 4611.
92. Castellano JM, Navarro VM, Fernandez-Fernandez R, Nogueiras R, Tovar S, Roa J, Vazquez MJ, Vigo E, Casanueva FF, Aguilar E, Pinilla L, Dieguez C, Tena-Sempere M. Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology 2005; 146:3917-3925.
93. Wahab F, Ullah F, Chan YM, Seminara SB, Shahab M. Decrease in hypothalamic Kiss1 and Kiss1r expression: a potential mechanism for fasting-induced suppression of the HPG axis in the adult male rhesus monkey (Macaca mulatta). Horm Metab Res 2011; 43:81-85.
94. Roa J, Garcia-Galiano D, Varela L, Sanchez-Garrido MA, Pineda R, Castellano JM, Ruiz-Pino F, Romero M, Aguilar E, Lopez M, Gaytan F, Dieguez C, et al. The mammalian target of rapamycin as novel central regulator of puberty onset via modulation of hypothalamic Kiss1 system. Endocrinology 2009; 150:5016-5026.
95. Yamada S, Uenoyama Y, Kinoshita M, Iwata K, Takase K, Matsui H, Adachi S, Inoue K, Maeda KI, Tsukamura H. Inhibition of metastin (kisspeptin-54)-GPR54 signaling in the arcuate nucleus-median emi- nence region during lactation in rats. Endocrinology 2007; 148:2226- 2232.
96. Castellano JM, Navarro VM, Fernandez-Fernandez R, Roa J, Vigo E, Pineda R, Dieguez C, Aguilar E, Pinilla L, Tena-Sempere M. Expression of hypothalamic KiSS-1 system and rescue of defective gonadotropic responses by kisspeptin in streptozotocin-induced diabetic male rats. Diabetes 2006; 55:2602-2610.
97. Castellano JM, Navarro VM, Roa J, Pineda R, Sanchez-Garrido MA, Garcia-Galiano D, Vigo E, Dieguez C, Aguilar E, Pinilla L, Tena- Sempere M. Alterations in hypothalamic KiSS-1 system in experimental diabetes: early changes and functional consequences. Endocrinology 2009; 150:784-794.
98. Smith JT, Acohido BV, Clifton DK, Steiner RA. KiSS-1 neurones are direct targets for leptin in the ob/ob mouse. J Neuroendocrinol 2006; 18:298-303.
99. Quennell JH, Howell CS, Roa J, Augustine RA, Grattan DR, Anderson GM. Leptin deficiency and diet-induced obesity reduce hypothalamic kisspeptin expression in mice. Endocrinology 2011; 152:1541-1550.
100. Backholer K, Smith JT, Rao A, Pereira A, Iqbal J, Ogawa S, Li Q, Clarke IJ. Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells. Endocrinology 2010; 151:2233-2243.
101. Altarejos JY, Goebel N, Conkright MD, Inoue H, Xie J, Arias CM, Sawchenko PE, Montminy M. The Creb1 coactivator Crtc1 is required for energy balance and fertility. Nat Med 2008; 14:1112-1117.
102. Roa J, Tena-Sempere M. Energy balance and puberty onset: emerging role of central mTOR signaling. Trends Endocrinol Metab 2010; 21:519-528.
103. Donato J Jr, Cravo RM, Frazao R, Gautron L, Scott MM, Lachey J, Castro IA, Margatho LO, Lee S, Lee C, Richardson JA, Friedman J, et al. Leptin's effect on puberty in mice is relayed by the ventral premammillary nucleus and does not require signaling in Kiss1 neurons. J Clin Invest 2011; 121:355-368.
104. Donato J Jr, Silva RJ, Sita LV, Lee S, Lee C, Lacchini S, Bittencourt JC, Franci CR, Canteras NS, Elias CF. The ventral premammillary nucleus links fasting-induced changes in leptin levels and coordinated luteinizing hormone secretion. J Neurosci 2009; 29:5240-5250.
105. Backholer K, Smith J, Clarke IJ. Melanocortins may stimulate reproduction by activating orexin neurons in the dorsomedial hypothal- amus and kisspeptin neurons in the preoptic area of the ewe. Endocrinology 2009; 150:5488-5497.
106. Kim GL, Dhillon SS, Belsham DD. Kisspeptin directly regulates neuropeptide Y synthesis and secretion via the ERK1/2 and p38 mitogen-activated protein kinase signaling pathways in NPY-secreting hypothalamic neurons. Endocrinology 2010; 151:5038-5047.
107. Fu LY, van den Pol AN. Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism. J Neurosci 2010; 30:10205- 10219.
108. Thompson EL, Patterson M, Murphy KG, Smith KL, Dhillo WS, Todd JF, Ghatei MA, Bloom SR. Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. J Neuroendocrinol 2004; 16:850-858.