Physiological roles of the kisspeptin/GPR54 system in the neuroendocrine control of reproduction

Progress in Brain Research

Volumn 181, Issue C, 2010, Pages 55-77

  Pineda, Rafael ^a   Aguilar, Enrique ^a   Pinilla, Leonor ^a   Tena Sempere, Manuel ^a  

^a UNIVERSITY OF CÓRDOBA   (Spain)

Author keywords

Feedback; Gnrh; Gonadotropins; Gpr54; Kiss1; Kiss1R; Kisspeptins; Ovulation; Puberty; Sex steroids

Indexed keywords

G PROTEIN COUPLED RECEPTOR 54; GONADOTROPIN; HORMONE; KISSPEPTIN; NEUROPEPTIDE; G PROTEIN COUPLED RECEPTOR; KISS1 PROTEIN, HUMAN; KISS1R PROTEIN, HUMAN; TUMOR SUPPRESSOR PROTEIN;

ARTICLE; ENVIRONMENTAL FACTOR; FEEDBACK SYSTEM; GONADOTROPIN RELEASE; HUMAN; HYPOTHALAMUS HYPOPHYSIS GONAD SYSTEM; MEDICAL LITERATURE; NEUROENDOCRINOLOGY; NONHUMAN; PHYSIOLOGY; PRIORITY JOURNAL; PUBERTY; REPRODUCTION; SEX DIFFERENTIATION; ANIMAL; ENVIRONMENT; GENETICS; HISTOLOGY; METABOLISM; NERVE CELL; NEUROSECRETION; REVIEW; SECRETION;

ANIMALS; ENVIRONMENT; GONADOTROPINS; HUMANS; NEURONS; NEUROPEPTIDES; NEUROSECRETORY SYSTEMS; PUBERTY; RECEPTORS, G-PROTEIN-COUPLED; REPRODUCTION; SEX DIFFERENTIATION; TUMOR SUPPRESSOR PROTEINS;

EID: 77955494533     PISSN: 00796123     EISSN: 18757855     Source Type: Book Series    
DOI: 10.1016/S0079-6123(08)81005-9     Document Type: Article

References (127)

1. Altarejos, J. Y., Goebel, N., Conkright, M. D., Inoue, H., Xie, J., Arias, C. M., et al. (2008). The Creb1 coactivator Crtc1 is required for energy balance and fertility. Nature Medicine, 14, 1112-1117.
2. Arai, A. C., Xia, Y. F., Suzuki, E., Kessler, M., Civelli, O., & Nothacker, H. P. (2005). Cancer metastasis-suppressing peptide metastin upregulates excitatory synaptic transmission in hippocampal dentate granule cells. Journal of Neurophysiology, 94, 3648-3652.
3. Backholer, K., Smith, J., & Clarke, I. J. (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.
4. Bellingham, M., Fowler, P., Amezaga, M., Rhind, A., Cotinot, C., Madon-Pepin, B., et al. (2009). Exposure to a complex cocktail of environmental endocrine disrupting compounds disturbs the kiss1/GPR54 system in ovine hypothalamus and pituitary gland. Environmental Health Perspectives, 117, 1556-1562. doi: 10.1289/eph. 0900699.
5. Brailoiu, G. C., Dun, S. L., Ohsawa, M., Yin, D., Yang, J., Chang, J. K., et al. (2005). KiSS-1 expression and metastinlike immunoreactivity in the rat brain. The Journal of Comparative Neurology, 481, 314-329.
6. Breuillaud, L., Halfon, O., Magistretti, P. J., Pralong, F. P., & Cardinaux, J. R. (2009). Mouse fertility is not dependent on the CREB coactivator Crtc1. Nature Medicine, 15, 989-990, author reply 991.
7. 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. Molecular and Cellular Endocrinology, 281, 64-72.
8. Castano, J. P., Martinez-Fuentes, A. J., Gutierrez-Pascual, E., Vaudry, H., Tena-Sempere, M., & Malagon, M. M. (2009). Intracellular signaling pathways activated by kisspeptins through GPR54: Do multiple signals underlie function diversity? Peptides, 30, 10-15.
9. Castellano, J. M., Gaytan, M., Roa, J., Vigo, E., Navarro, V. M., Bellido, C., et al. (2006a). Expression of KiSS-1 in rat ovary: Putative local regulator of ovulation? Endocrinology, 147, 4852-4862.
10. Castellano, J. M., Navarro, V. M., Fernandez-Fernandez, R., Castano, J. P., Malagon, M. M., Aguilar, E., et al. (2006b). Ontogeny and mechanisms of action for the stimulatory effect of kisspeptin on gonadotropin-releasing hormone system of the rat. Molecular and Cellular Endocrinology, 257-258, 75-83.
11. Castellano, J. M., Navarro, V. M., Fernandez-Fernandez, R., Nogueiras, R., Tovar, S., Roa, J., 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.
12. Castellano, J. M., Navarro, V. M., Fernandez-Fernandez, R., Roa, J., Vigo, E., Pineda, R., et al. (2006c). Expression of hypothalamic KiSS-1 system and rescue of defective gonadotropic responses by kisspeptin in streptozotocin-induced diabetic male rats. Current Medical Literature -Diabetes, 55, 2602-2610.
13. Castellano, J. M., Navarro, V. M., Roa, J., Pineda, R., Sanchez-Garrido, M. A., Garcia-Galiano, D., et al. (2009a). Alterations in hypothalamic KiSS-1 system in experimental diabetes: Early changes and functional consequences. Endocrinology, 150, 784-794.
14. Castellano, J. M., Roa, J., Luque, R. M., Dieguez, C., Aguilar, E., Pinilla, L., et al. (2009b). KiSS-1/kisspeptins and the metabolic control of reproduction: Physiologic roles and putative physiopathological implications. Peptides, 30, 139-145.
15. Cheng, G., Coolen, L. M., Padmanabhan, V., Goodman, R. L., & Lehman, M. N. (2010). The kisspeptin/neurokinin B/ dynorphin (KNDy) cell population of the arcuate nucleus: Sex differences and effects of prenatal testosterone in the sheep. Endocrinology, 151, 301-311.
16. Clarke, I. J., Smith, J. T., Caraty, A., Goodman, R. L., & Lehman, M. N. (2009). Kisspeptin and seasonality in sheep. Peptides, 30, 154-163.
17. Clarkson, J., Boon, W. C., Simpson, E. R., & Herbison, A. E. (2009a). Postnatal development of an estradiol-kisspeptin positive feedback mechanism implicated in puberty onset. Endocrinology, 150, 3214-3220.
18. Clarkson, J., d'Anglemont de Tassigny, X., Moreno, A. S., Colledge, W. H., & Herbison, A. E. (2008). Kisspeptin-GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge. Journal of Neuroscience, 28, 8691-8697.
19. Clarkson, J., d'Anglemont de Tassigny, X., Colledge, W. H., Caraty, A., & Herbison, A. E. (2009b). Distribution of kisspeptin neurons in the adult female mouse brain. Journal of Neuroendocrinology, 21, 673-682.
20. Clarkson, J. & Herbison, A. E. (2006). Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons. Endocrinology, 147, 5817-5825.
21. Cota, D., Proulx, K., Smith, K. A., Kozma, S. C., Thomas, G., Woods, S. C., et al. (2006). Hypothalamic mTOR signaling regulates food intake. Science, 312, 927-930.
22. Curtis, A. E., Cooke, J. H., Baxter, J. E., Parkinson, J. R., Bataveljic, A. S., Ghatei, M. A., et al. (2010). A kisspeptin-10 analogue with greater in vivo bioactivity than kisspeptin-10. American Journal of Physiology Endocrinology Metabolism, 298, E296-E303.
23. d'Anglemont de Tassigny, X., Fagg, L. A., Carlton, M. B., & Colledge, W. H. (2008). Kisspeptin can stimulate gonadotropin-releasing hormone (GnRH) release by a direct action at GnRH nerve terminals. Endocrinology, 149, 3926-3932.
24. d'Anglemont de Tassigny, X., Fagg, L. A., Dixon, J. P., Day, K., Leitch, H. G., Hendrick, A. G., et al. (2007). Hypogonadotropic hypogonadism in mice lacking a functional kiss1 gene. Proceedings of the National Academy of Sciences of the United States of America, 104, 10714-10719.
25. de Roux, N., Genin, E., Carel, J. C., Matsuda, F., Chaussain, J. L., & Milgrom, E. (2003). Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proceedings of the National Academy of Sciences of the United States of America, 100, 10972-10976.
26. Decourt, C., Tillet, Y., Caraty, A., Franceschini, I., & Briant, C. (2008). Kisspeptin immunoreactive neurons in the equine hypothalamus interactions with GnRH neuronal system. Journal of Chemical Neuroanatomy, 36, 131-137.
27. Dhillo, W. S., Chaudhri, O. B., Patterson, M., Thompson, E. L., Murphy, K. G., Badman, M. K., et al. (2005). Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. Journal of Clinical Endocrinology Metabolism, 90, 6609-6615.
28. Dhillo, W. S., Chaudhri, O. B., Thompson, E. L., Murphy, K. G., Patterson, M., Ramachandran, R., et al. (2007). Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women. Journal of Clinical Endocrinology Metabolism, 92, 3958-3966.
29. Dungan, H. M., Gottsch, M. L., Zeng, H., Gragerov, A., Bergmann, J. E., Vassilatis, D. K., et al. (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.
30. Felip, A., Zanuy, S., Pineda, R., Pinilla, L., Carrillo, M., Tena-Sempere, M., et al. (2009). Evidence for two distinct KiSS genes in non-placental vertebrates that encode kisspeptins with different gonadotropin-releasing activities in fish and mammals. Molecular and Cellular Endocrinology, 312, 61-71.
31. Forbes, S., Li, X. F., Kinsey-Jones, J., & O'byrne, K. (2009). Effects of ghrelin on kisspeptin mRNA expression in the hypothalamic medial preoptic area and pulsatile luteinising hormone secretion in the female rat. Neuroscience Letters, 460, 143-147.
32. Funes, S., Hedrick, J. A., Vassileva, G., Markowitz, L., Abbondanzo, S., Golovko, A., et al. (2003). The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochemical and Biophysical Research Communications, 312, 1357-1363.
33. Gaytan, F., Gaytan, M., Castellano, J. M., Romero, M., Roa, J., Aparicio, B., 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 Metabolism, 296, E520-E531.
34. Gonzalez-Martinez, D., deMees, C., Douhard, Q., Szpirer, C., & Bakker, J. (2008). Absence of gonadotropin-releasing hormone 1 and kiss1 activation in alpha-fetoprotein knockout mice: Prenatal estrogens defeminize the potential to show preovulatory luteinizing hormone surges. Endocrinology, 149, 2333-2340.
35. Goodman, R. L., Lehman, M. N., Smith, J. T., Coolen, L. M., de Oliveira, C. V., Jafarzadehshirazi, M. R., et al. (2007). Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphinAand neurokininB. Endocrinology, 148, 5752-5760.
36. Gottsch, M. L., Clifton, D. K., & Steiner, R. A. (2009a). From KISS1 to kisspeptins: An historical perspective and suggested nomenclature. Peptides, 30, 4-9.
37. Gottsch, M. L., Cunningham, M. J., Smith, J. T., Popa, S. M., Acohido, B. V., Crowley, W. F., et al. (2004). A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology, 145, 4073-4077.
38. Gottsch, M. L., Navarro, V. M., Zhao, Z., Glidewell-Kenney, C., Weiss, J., Jameson, J. L., et al. (2009b). Regulation of kiss1 and dynorphin gene expression in the murine brain by classical and nonclassical estrogen receptor pathways. Journal of Neuroscience, 29, 9390-9395.
39. Greives, T. J., Mason, A. O., Scotti, M. A., Levine, J., Ketterson, E. D., Kriegsfeld, L. J., et al. (2007). Environmental control of kisspeptin: Implications for seasonal reproduction. Endocrinology, 148, 1158-1166.
40. Gutierrez-Pascual, E., Leprince, J., Martinez-Fuentes, A. J., Segalas-Milazzo, I., Pineda, R., Roa, J., et al. (2009). In vivo and in vitro structure-activity relationships and structural conformation of kisspeptin-10-related peptides. Molecular Pharmacology, 76, 58-67.
41. Gutierrez-Pascual, E., Martinez-Fuentes, A. J., Pinilla, L., Tena-Sempere, M., Malagon, M. M., & Castano, J. P. (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.
42. Han, S. K., Gottsch, M. L., Lee, K. J., Popa, S. M., Smith, J. T., Jakawich, S. K., et al. (2005). Activation of gonadotropinreleasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. Journal of Neuroscience, 25, 11349-11356.
43. Herbison, A. E. (2006). Physiology of the gonadotropin-releasing hormone neuronal network. In J. D. Neill (Ed.), The Physiology of Reproduction. Elsevier/Academic Press, San Diego (USA).
44. Herbison, A. E., d'Anglemont de Tassigny, X., Doran, J., & Colledge, W. H. (2010). Distribution and postnatal development of GPR54 gene expression in mouse brain and gonadotropin-releasing hormone neurons. Endocrinology, 151, 312-321.
45. Hiney, J. K., Srivastava, V. K., Pine, M. D., & Les Dees, W. (2009). Insulin-like growth factor-I activates KiSS-1 gene expression in the brain of the prepubertal female rat. Endocrinology, 150, 376-384.
46. Homma, T., Sakakibara, M., Yamada, S., Kinoshita, M., Iwata, K., Tomikawa, J., et al. (2009). Significance of neonatal testicular sex steroids to defeminize anteroventral periventricular kisspeptin neurons and the GnRH/LH surge system in male rats. Biology of Reproduction, 81, 1216-1225.
47. Irwig, M. S., Fraley, G. S., Smith, J. T., Acohido, B. V., Popa, S. M., Cunningham, M. J., et al. (2004). Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat. Neuroendocrinology, 80, 264-272.
48. Jacobi, J. S., Martin, C., Nava, G., Jeziorski, M. C., Clapp, C., & MartinezDeLaEscalera, G. (2007). 17-Beta-estradiol directly regulates the expression of adrenergic receptors and kisspeptin/ GPR54 system in GT1-7 GnRH neurons. Neuroendocrinology, 86, 260-269.
49. Kauffman, A. S., Gottsch, M. L., Roa, J., Byquist, A. C., Crown, A., Clifton, D. K., et al. (2007). Sexual differentiation of kiss1 gene expression in the brain of the rat. Endocrinology, 148, 1774-1783.
50. Kauffman, A. S., Navarro, V. M., Kim, J., Clifton, D., & Steiner, R. A. (2010). Sex differences in the regulation of kiss1/NKB neurons in juvenile mice: Implications for the timing of puberty. American Journal of Physiology Endocrinology Metabolism. (in press).
51. Kinoshita, M., Tsukamura, H., Adachi, S., Matsui, H., Uenoyama, Y., Iwata, K., 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.
52. Kinsey-Jones, J. S., Li, X. F., Knox, A. M., Wilkinson, E. S., Zhu, X. L., Chaudhary, A. A., et al. (2009). Down-regulation of hypothalamic kisspeptin and its receptor, kiss1r, mRNA expression is associated with stress-induced suppression of luteinising hormone secretion in the female rat. Journal of Neuroendocrinology, 21, 20-29.
53. Kotani, M., Detheux, M., Vandenbogaerde, A., Communi, D., Vanderwinden, J. M., Le Poul, E., et al. (2001). The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. The Journal of Biological Chemistry, 276, 34631-34636.
54. Kriegsfeld, L. J. (2006). Driving reproduction: RFamide peptides behind the wheel. Hormones and Behavior, 50, 655-666.
55. Lapatto, R., Pallais, J. C., Zhang, D., Chan, Y. M., Mahan, A., Cerrato, F., et al. (2007). Kiss1/mice exhibit more variable hypogonadism than GPR54/mice. Endocrinology, 148, 4927-4936.
56. Lederman, M. A., Lebesgue, D., Gonzalez, V. V., Shu, J., Merhi, Z. O., Etgen, A. M., et al. (2009). Age-related LH surge dysfunction correlates with reduced responsiveness of hypothalamic anteroventral periventricular nucleus kisspeptin neurons to estradiol positive feedback in middle-aged rats. Neuropharmacology, 58, 314-320.
57. Lee, J. H., Miele, M. E., Hicks, D. J., Phillips, K. K., Trent, J. M., Weissman, B. E., et al. (1996). KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. Journal of the National Cancer Institute, 88, 1731-1737.
58. Lee, D. K., Nguyen, T., O'Neill, G. P., Cheng, R., Liu, Y., Howard, A. D., et al. (1999). Discovery of a receptor related to the galanin receptors. FEBS Letters, 446, 103-107.
59. Lee, Y. R., Tsunekawa, K., Moon, M. J., Um, H. N., Hwang, J. I., Osugi, T., et al. (2009). Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates. Endocrinology, 150, 2837-2846.
60. Liu, X., Lee, K., & Herbison, A. E. (2008). Kisspeptin excites gonadotropin-releasing hormone neurons through a phospholipase C/calcium-dependent pathway regulating multiple ion channels. Endocrinology, 149, 4605-4614.
61. Luan, X., Yu, H., Wei, X., Zhou, Y., Wang, W., Li, P., et al. (2007a). GPR54 polymorphisms in Chinese girls with central precocious puberty. Neuroendocrinology, 86, 77-83.
62. Luan, X., Zhou, Y., Wang, W., Yu, H., Li, P., Gan, X., et al. (2007b). Association study of the polymorphisms in the KISS1 gene with central precocious puberty in Chinese girls. European Journal of Endocrinology, 157, 113-118.
63. Luque, R. M., Kineman, R. D., & Tena-Sempere, M. (2007). Regulation of hypothalamic expression of KiSS-1 and GPR54 genes by metabolic factors: Analyses using mouse models and a cell line. Endocrinology, 148, 4601-4611.
64. Matsui, H., Takatsu, Y., Kumano, S., Matsumoto, H., & Ohtaki, T. (2004). Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat. Biochemical and Biophysical Research Communications, 320, 383-388.
65. Mead, E. J., Maguire, J. J., Kuc, R. E., & Davenport, A. P. (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.
66. Mechaly, A. S., Vinas, J., & Piferrer, F. (2009b). Identification of two isoforms of the kisspeptin-1 receptor (kiss1r) generated by alternative splicing in a modern teleost, the Senegalese sole (Solea senegalensis). Biology of Reproduction, 80, 60-69.
67. Mechaly, A. S., Vinas, J., Murphy, C., Reith, M., & Piferrer, F. (2010). Gene structure of the kiss1 receptor-2 (kiss1r-2) in the Atlantic halibut: Insights into the evolution and regulation of kiss1r genes. Molecular and Cellular Endocrinology, 317, 78-89.
68. Messager, S., Chatzidaki, E. E., Ma, D., Hendrick, A. G., Zahn, D., Dixon, J., et al. (2005). Kisspeptin directly stimulates gonadotropin-releasing hormone release via G proteincoupled receptor 54. Proceedings of the National Academy of Sciences of the United States of America, 102, 1761-1766.
69. Mikkelsen, J. D. & Simonneaux, V. (2009). The neuroanatomy of the kisspeptin system in the mammalian brain. Peptides, 30, 26-33.
70. Muir, A. I., Chamberlain, L., Elshourbagy, N. A., Michalovich, D., Moore, D. J., Calamari, A., et al. (2001). AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. The Journal of Biological Chemistry, 276, 28969-28975.
71. Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Barreiro, M. L., Roa, J., Sanchez-Criado, J. E., et al. (2004a). 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, 4565-4574.
72. Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Roa, J., Mayen, A., et al. (2005a). Effects of KiSS-1 peptide, the natural ligand of GPR54, on follicle-stimulating hormone secretion in the rat. Endocrinology, 146, 1689-1697.
73. Navarro,V.M., Castellano, J. M.,Fernandez-Fernandez,R.,Tovar, S., Roa, J., Mayen, A., et al. (2005b). Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand ofGPR54. Endocrinology, 146, 156-163.
74. Navarro, V. M., Fernandez-Fernandez, R., Castellano, J. M., Roa, J., Mayen, A., Barreiro, M. L., et al. (2004b). Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54. Journal of Physiology (Paris), 561, 379-386.
75. Navarro, V. M., Gottsch, M. L., Chavkin, C., Okamura, H., Clifton, D. K., & Steiner, R. A. (2009a). 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.
76. Navarro, V. M., Sanchez-Garrido, M. A., Castellano, J. M., Roa, J., Garcia-Galiano, D., Pineda, R., et al. (2009b). Persistent impairment of hypothalamic KiSS-1 system after exposures to estrogenic compounds at critical periods of brain sex differentiation. Endocrinology, 150, 2359-2367.
77. Nazian, S. J. (2006). Role of metastin in the release of gonadotropin-releasing hormone from the hypothalamus of the male rat. Journal of Andrology, 27, 444-449.
78. Novaira, H. J., 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.
79. Oakley, A. E., Clifton, D. K., & Steiner, R. A. (2009). Kisspeptin signaling in the brain. Endocrine Reviews, 30, 713-743.
80. Ohtaki, T., Shintani, Y., Honda, S., Matsumoto, H., Hori, A., Kanehashi, K., et al. (2001). Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature, 411, 613-617.
81. Ojeda, S. R., Lomniczi, A., & Sandau, U. S. (2008). Glialgonadotrophin hormone (GnRH) neuron interactions in the median eminence and the control of GnRH secretion. Journal of Neuroendocrinology, 20, 732-742.
82. Pampillo, M., Camuso, N., Taylor, J. E., Szereszewski, J. M., Ahow, M. R., Zajac, M., et al. (2009). Regulation of GPR54 signaling by GRK2 and {beta}-arrestin. Molecular Endocrinology, 23, 2060-2074.
83. Paul, M. J., Pyter, L. M., Freeman, D. A., Galang, J., & Prendergast, B. J. (2009). Photic and nonphotic seasonal cues differentially engage hypothalamic kisspeptin and RFamide-related peptide mRNA expression in Siberian hamsters. Journal of Neuroendocrinology, 21, 1007-1014.
84. Pielecka-Fortuna, J., Chu, Z., & Moenter, S. M. (2008). Kisspeptin acts directly and indirectly to increase GnRH neuron activity and its effects are modulated by estradiol. Endocrinology, 149, 1979-1986.
85. Pielecka-Fortuna, J. & Moenter, S. M. (2010). Kisspeptin increases {gamma}-aminobutyric acidergic and glutamatergic transmission directly to gonadotropin-releasing hormone neurons in an estradiol-dependent manner. Endocrinology, 151, 291-300.
86. Pineda, R., Garcia-Galiano, D., Roseweir, A., Romero, M., Sanchez-Garrido, M. A., Ruiz-Pino, F., et al. (2010). Critical roles of kisspeptins in female puberty and preovulatory gonadotropin surges as revealed by a novel antagonist. Endocrinology, 151, 722-730.
87. Plant, T. M., Ramaswamy, S., & Dipietro, M. J. (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.
88. Quaynor, S., Hu, L., Leung, P. K., Feng, H., Mores, N., Krsmanovic, L. Z., et al. (2007). Expression of a functional G protein-coupled receptor 54-kisspeptin autoregulatory system in hypothalamic gonadotropin-releasing hormone neurons. Molecular Endocrinology, 21, 3062-3070.
89. Quennell, J. H., Mulligan, A. C., Tups, A., Liu, X., Phipps, S. J., Kemp, C. J., et al. (2009). Leptin indirectly regulates gonadotropin-releasing hormone neuronal function. Endocrinology, 150, 2805-2812.
90. Ramaswamy, S., Gibbs, R. B., & Plant, T. M. (2009). Studies of the localisation of kisspeptin within the pituitary of the rhesus monkey (Macaca mulatta) and the effect of kisspeptin on the release of non-gonadotropic pituitary hormones. Journal of Neuroendocrinology, 21, 795-804.
91. Revel, F. G., Ansel, L., Klosen, P., Saboureau, M., Pevet, P., Mikkelsen, J. D., et al. (2007). Kisspeptin: A key link to seasonal breeding. Reviews in Endocrine & Metabolic Disorders, 8, 57-65.
92. Revel, F. G., Masson-Pevet, M., Pevet, P., Mikkelsen, J. D., & Simonneaux, V. (2009). Melatonin controls seasonal breeding by a network of hypothalamic targets. Neuroendocrinology, 90, 1-14.
93. Revel, F. G., Saboureau, M., Masson-Pevet, M., Pevet, P., Mikkelsen, J. D., & Simonneaux, V. (2006). Kisspeptin mediates the photoperiodic control of reproduction in hamsters. Current Biology, 16, 1730-1735.
94. Richard, N., Galmiche, G., Corvaisier, S., Caraty, A., & Kottler, M. L. (2008). KiSS-1 and GPR54 genes are co-expressed in rat gonadotrophs and differentially regulated in vivo by oestradiol and gonadotrophinreleasing hormone. Journal of Neuroendocrinology, 20, 381-393.
95. Roa, J., Aguilar, E., Dieguez, C., Pinilla, L., & Tena-Sempere, M. (2008a). New frontiers in kisspeptin/GPR54 physiology as fundamental gatekeepers of reproductive function. Frontiers in Neuroendocrinology, 29, 48-69.
96. Roa, J., Castellano, J. M., Navarro, V. M., Handelsman, D. J., Pinilla, L., & Tena-Sempere, M. (2009a). Kisspeptins and the control of gonadotropin secretion in male and female rodents. Peptides, 30, 57-66.
97. Roa, J., Garcia-Galiano, D., Varela, L., Sanchez-Garrido,M. A., Pineda, R., Castellano, J. M., et al. (2009b). The mammalian target of rapamycin as novel central regulator of puberty onset via modulation of hypothalamic kiss1 system. Endocrinology, 150, 5016-5026.
98. Roa, J., Vigo, E., Castellano, J. M., Gaytan, F., Garcia-Galiano, D., Navarro, V. M., et al. (2008b). Follicle-stimulating hormone responses to kisspeptin in the female rat at the preovulatory period: Modulation by estrogen and progesterone receptors. Endocrinology, 149, 5783-5790.
99. Roa, J., Vigo, E., Castellano, J. M., Gaytan, F., Navarro, V. M., Aguilar, E., et al. (2008c). 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, 1627-1637.
100. Roa, J., Vigo, E., Castellano, J. M., Navarro, V. M., Fernandez-Fernandez, R., Casanueva, F. F., et al. (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.
101. Rometo, A. M., Krajewski, S. J., Voytko, M. L., & Rance, N. E. (2007). Hypertrophy and increased kisspeptin gene expression in the hypothalamic infundibular nucleus of postmenopausal women and ovariectomized monkeys. Journal of Clinical Endocrinology Metabolism, 92, 2744-2750.
102. Roseweir, A. K.,Kauffman, A. S., Smith, J. T., Guerriero, K. A., Morgan, K., Pielecka-Fortuna, J., et al. (2009). Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation. Journal of Neuroscience, 29, 3920-3929.
103. Schwartz, N. B. (2000). Neuroendocrine regulation of reproductive cyclicity. In P. M. Conn & M. E. Freeman (Eds.), Neuroendocrinology in Physiology and Medicine. Totowa, NJ: Humana Press.
104. Schwartz, M. W., Seeley, R. J., Campfield, L. A., Burn, P., & Baskin, D. G. (1996). Identification of targets of leptin action in rat hypothalamus. The Journal of Clinical Investigation, 98, 1101-1106.
105. Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S. Jr., Shagoury, J. K., et al. (2003). The GPR54 gene as a regulator of puberty. The New England Journal of Medicine, 349, 1614-1627.
106. Shahab, M., Mastronardi, C., Seminara, S. B., Crowley, W. F., Ojeda, S. R., & Plant, T. M. (2005). Increased hypothalamic GPR54 signaling: A potential mechanism for initiation of puberty in primates. Proceedings of the National Academy of Sciences of the United States of America, 102, 2129-2134.
107. Simonneaux, V., Ansel, L., Revel, F. G., Klosen, P., Pevet, P., & Mikkelsen, J. D. (2009). Kisspeptin and the seasonal control of reproduction in hamsters. Peptides, 30, 146-153.
108. Smith, J. T., Acohido, B. V., Clifton, D. K., & Steiner, R. A. (2006a). KiSS-1 neurons are direct targets for leptin in the ob/ob mouse. Journal of Neuroendocrinology, 18, 298-303.
109. Smith, J. T., Coolen, L. M., Kriegsfeld, L. J., Sari, I. P., Jaafarzadehshirazi, M. R., Maltby, M., et al. (2008). Variation in kisspeptin and RFamide-related peptide (RFRP) expression and terminal connections to gonadotropinreleasing hormone neurons in the brain: A novel medium for seasonal breeding in the sheep. Endocrinology, 149, 5770-5782.
110. Smith, J. T., Cunningham, M. J., Rissman, E. F., Clifton, D. K., & Steiner, R. A. (2005a). Regulation of kiss1 gene expression in the brain of the femalemouse. Endocrinology, 146, 3686-3692.
111. Smith, J. T., Dungan, H. M., Stoll, E. A., Gottsch, M. L., Braun, R. E., Eacker, S. M., et al. (2005b). Differential regulation of KiSS-1 mRNA expression by sex steroids in the brain of the male mouse. Endocrinology, 146, 2976-2984.
112. Smith, J. T., Popa, S. M., Clifton, D. K., Hoffman, G. E., & Steiner, R. A. (2006b). Kiss1 neurons in the forebrain as central processors for generating the preovulatory luteinizing hormone surge. Journal of Neuroscience, 26, 6687-6694.
113. Smith, J. T., Rao, A., Pereira, A., Caraty, A., Millar, R. P., & Clarke, I. J. (2007). 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, 1951-1955.
114. Suzuki, S., Kadokawa, H., & Hashizume, T. (2008). Direct kisspeptin-10 stimulation on luteinizing hormone secretion from bovine and porcine anterior pituitary cells. Animal Reproduction Science, 103, 360-365.
115. Takahashi, K., Shoji, I., Shibasaki, A., Kato, I., Hiraishi, K., Yamamoto, H., et al. (2010). Presence of kisspeptin-like immunoreactivity in human adrenal glands and adrenal tumors. Journal of Molecular Neuroscience, (in press).
116. Teles, M. G., Bianco, S. D., Brito, V. N., Trarbach, E. B., Kuohung, W., Xu, S., et al. (2008). A GPR54-activating mutation in a patient with central precocious puberty. The New England Journal of Medicine, 358, 709-715.
117. Tena-Sempere, M. (2008). Ghrelin as a pleotrophic modulator of gonadal function and reproduction. Nature Clinical Practice Endocrinology and Metabolism, 4, 666-674.
118. Tena-Sempere, M. & Huhtaniemi, I. (2003). Gonadotropins and gonadotropin receptors. In B. C.J.M. Fauser (Ed.), Reproductive Medicine -Molecular, Cellular and Genetic Fundamentals. New York: Parthenon Publishing.
119. Tena-Sempere, M., Pinilla, L., Gonzalez, L. C., & Aguilar, E. (2000). Reproductive disruption by exposure to exogenous estrogenic compounds during sex differentiation: Lessons from the neonatally estrogenized male rat. Current Topics Steroid Research, 3, 23-37.
120. Thompson, E. L., Patterson, M., Murphy, K. G., Smith, K. L., Dhillo, W. S., Todd, J. F., et al. (2004). Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. Journal of Neuroendocrinology, 16, 850-858.
121. Todd, B. J., Fraley, G. S., Peck, A. C., Schwartz, G. J., & Etgen, A. M. (2007). Central insulin-like growth factor 1 receptors play distinct roles in the control of reproduction, food intake, and body weight in female rats. Biology of Reproduction, 77, 492-503.
122. Tomikawa, J., Homma, T., Tajima, S., Shibata, T., Inamoto, Y., Takase, K., et al. (2010). Molecular characterization and estrogen regulation of hypothalamic KISS1 gene in the pig. Biology of Reproduction, 82, 313-319.
123. Topaloglu, A. K., Reimann, F., Guclu, M., Yalin, A. S., Kotan, L. D., Porter, K. M., 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.
124. Tovar, S., Vazquez,M. J., Navarro, V.M., Fernandez-Fernandez, R., Castellano, J. M., Vigo, E., et al. (2006). Effects of single or repeated intravenous administration of kisspeptin upon dynamic LH secretion in conscious male rats. Endocrinology, 147, 2696-2704.
125. Wacker, J. L., Feller, D. B., Tang, X. B., Defino, M. C., Namkung, Y., Lyssand, J. S., et al. (2008). Disease-causing mutation in GPR54 reveals the importance of the second intracellular loop for class A G-protein-coupled receptor function. The Journal of Biological Chemistry, 283, 31068-31078.
126. Wu, M., Dumalska, I., Morozova, E., Van Den Pol, A., & Alreja, M. (2009). Melanin-concentrating hormone directly inhibits GnRH neurons and blocks kisspeptin activation, linking energy balance to reproduction. Proceedings of the National Academy of Sciences of the United States of America, 106, 17217-17222.
127. Zhang, C., Roepke, T. A., Kelly, M. J., & Ronnekleiv, O. K. (2008). Kisspeptin depolarizes gonadotropin-releasing hormone neurons through activation of TRPC-like cationic channels. Journal of Neuroscience, 28, 4423-4434.