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Kisspeptins and Reproduction: Physiological Roles and Regulatory Mechanisms
Open accessAbstract
Procreation is essential for survival of species. Not surprisingly, complex neuronal networks have evolved to mediate the diverse internal and external environmental inputs that regulate reproduction in vertebrates. Ultimately, these regulatory factors impinge, directly or indirectly, on a final common pathway, the neurons producing the gonadotropin-releasing hormone (GnRH), which stimulates pituitary gonadotropin secretion and thereby gonadal function. Compelling evidence, accumulated in the last few years, has revealed that kisspeptins, a family of neuropeptides encoded by the Kiss1 gene and produced mainly by neuronal clusters at discrete hypothalamic nuclei, are pivotal upstream regulators of GnRH neurons. As such, kisspeptins have emerged as important gatekeepers of key aspects of reproductive maturation and function, from sexual differentiation of the brain and puberty onset to adult regulation of gonadotropin secretion and the metabolic control of fertility. This review aims to provide a comprehensive account of the state-of-the-art in the field of kisspeptin physiology by covering in-depth the consensus knowledge on the major molecular features, biological effects, and mechanisms of action of kisspeptins in mammals and, to a lesser extent, in nonmammalian vertebrates. This review will also address unsolved and contentious issues to set the scene for future research challenges in the area. By doing so, we aim to endow the reader with a critical and updated view of the physiological roles and potential translational relevance of kisspeptins in the integral control of reproductive function.
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The GPR54 Gene as a Regulator of Puberty
Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa035322 · Cited by 2,557
Central nervous system control of food intake and body weight
Morton, G. J., Cummings, D. E., Baskin, D. G., Barsh, G. S., & Schwartz, M. W. (2006) · Nature · doi:10.1038/nature05026 · Cited by 2,503
Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54
de Roux, N., Genin, E., Carel, J.-C., Matsuda, F., Chaussain, J.-L., & Milgrom, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834399100 · Cited by 2,431 · cited 5×
“in patients with hypogonadotropic hypogonadism (95).”
BackgroundResultInfluentialParent, A.-S., Teilmann, G., Juul, A., Skakkebaek, N. E., Toppari, J., & Bourguignon, J.-P. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0019 · Cited by 1,762
PGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure
Cantó, C., & Auwerx, J. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328328d0a4 · Cited by 1,624
Kotani, M., Detheux, M., Vandenbogaerde, A., Communi, D., Vanderwinden, J.-M., Le Poul, E., Brézillon, S., Tyldesley, R., Suarez-Huerta, N., Vandeput, F., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104847200 · Cited by 1,546
Biological, Physiological, Pathophysiological, and Pharmacological Aspects of Ghrelin
van der Lely, A. J., Tschöp, M., Heiman, M. L., & Ghigo, E. (2004) · Endocrine Reviews · doi:10.1210/er.2002-0029 · Cited by 1,187
Regulation of matrix biology by matrix metalloproteinases
Mott, J. D., & Werb, Z. (2004) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2004.07.010 · Cited by 1,104 · cited 1×
“For example, matrix metalloproteases (MMPs) have been implicated in tumor metastasis (506, 512) and trophoblast invasion (71), likely due to their ability to affect cellular interactions with the extracellular matrix, and hence cell division, migration, and morphogenesis (290).”
BackgroundRegulation of Kiss1 gene expression in the brain of the female mouse
Smith, J. T., Cunningham, M. J., Rissman, E. F., Clifton, D. K., & Steiner, R. A. (2005) · Endocrinology · doi:10.1210/en.2005-0488 · Cited by 1,102
KiSS-1, a Novel Human Malignant Melanoma Metastasis-Suppressor Gene
Lee, J.-H., Miele, M. E., Hicks, D. J., Phillips, K. K., Trent, J. M., Weissman, B. E., & Welch, D. R. (1996) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/88.23.1731 · Cited by 1,072
Han, S.-K., Gottsch, M. L., Lee, K. J., Popa, S. M., Smith, J. T., Jakawich, S. K., Clifton, D. K., Steiner, R. A., & Herbison, A. E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3328-05.2005 · Cited by 1,036
Topaloglu, A. K., Reimann, F., Guclu, M., Yalin, A. S., Kotan, L. D., Porter, K. M., Serin, A., Mungan, N. O., Cook, J. R., Ozbek, M. N., et al. (2009) · Nature Genetics · doi:10.1038/ng.306 · Cited by 961
Recombinant human leptin in women with hypothalamic amenorrhea
Welt, C. K., Chan, J. L., Bullen, J., Murphy, R., Smith, P., DePaoli, A. M., Karalis, A., & Mantzoros, C. S. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040388 · Cited by 908
Lehman, M. N., Coolen, L. M., & Goodman, R. L. (2010) · Endocrinology · doi:10.1210/en.2010-0022 · Cited by 768
Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B
Goodman, R. L., Lehman, M. N., Smith, J. T., Coolen, L. M., de Oliveira, C. V. R., Jafarzadehshirazi, M. R., Pereira, A., Iqbal, J., Caraty, A., Ciofi, P., et al. (2007) · Endocrinology · doi:10.1210/en.2007-0961 · Cited by 692
The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system
Funes, S., Hedrick, J. A., Vassileva, G., Markowitz, L., Abbondanzo, S., Golovko, A., Yang, S., Monsma, F. J., & Gustafson, E. L. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.11.066 · Cited by 675
Sexual differentiation of the vertebrate nervous system
Morris, J. A., Jordan, C. L., & Breedlove, S. M. (2004) · Nature Neuroscience · doi:10.1038/nn1325 · Cited by 627
Wakabayashi, Y., Nakada, T., Murata, K., Ohkura, S., Mogi, K., Navarro, V. M., Clifton, D. K., Mori, Y., Tsukamura, H., Maeda, K.-I., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5848-09.2010 · Cited by 597 · cited 5×
“Thereafter, the presence of such KNDy neurons has been documented by a combination of in situ hybridization and IHC techniques in the mouse, goat, and monkey, although in the latter only NKB coexpression was analyzed (304, 305, 363, 491).”
BackgroundMethodInfluentialADACHI, S., YAMADA, S., TAKATSU, Y., MATSUI, H., KINOSHITA, M., TAKASE, K., SUGIURA, H., OHTAKI, T., MATSUMOTO, H., UENOYAMA, Y., et al. (2007) · Journal of Reproduction and Development · doi:10.1262/jrd.18146 · Cited by 580
A GPR54 -Activating Mutation in a Patient with Central Precocious Puberty
Teles, M. G., Bianco, S. D. C., Brito, V. N., Trarbach, E. B., Kuohung, W., Xu, S., Seminara, S. B., Mendonca, B. B., Kaiser, U. B., & Latronico, A. C. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa073443 · Cited by 572
Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat
Matsui, H., Takatsu, Y., Kumano, S., Matsumoto, H., & Ohtaki, T. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.05.185 · Cited by 520
de Roux, N., Young, J., Misrahi, M., Genet, R., Chanson, P., Schaison, G., & Milgrom, E. (1997) · New England Journal of Medicine · doi:10.1056/nejm199711273372205 · Cited by 518
Inactivating KISS1 Mutation and Hypogonadotropic Hypogonadism
Topaloglu, A. K., Tello, J. A., Kotan, L. D., Ozbek, M. N., Yilmaz, M. B., Erdogan, S., Gurbuz, F., Temiz, F., Millar, R. P., & Yuksel, B. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1111184 · Cited by 467
Self-citationNavarro, V. M., Castellano, J. M., Fernández-Fernández, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J., Barreiro, M. L., Magni, P., et al. (2005) · Endocrinology · doi:10.1210/en.2004-0836 · Cited by 449
Self-citationChildhood obesity and the timing of puberty
Ahmed, M. L., Ong, K. K., & Dunger, D. B. (2009) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2009.02.004 · Cited by 409
Smith, J. T., Clay, C. M., Caraty, A., & Clarke, I. J. (2007) · Endocrinology · doi:10.1210/en.2006-1435 · Cited by 404
Rometo, A. M., Krajewski, S. J., Lou Voytko, M., & Rance, N. E. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0553 · Cited by 396
Knobil, E., Plant, T. M., Wildt, L., Belchetz, P. E., & Marshall, G. (1980) · Science · doi:10.1126/science.6766566 · Cited by 390
Roseweir, A. K., Kauffman, A. S., Smith, J. T., Guerriero, K. A., Morgan, K., Pielecka-Fortuna, J., Pineda, R., Gottsch, M. L., Tena-Sempere, M., Moenter, S. M., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5740-08.2009 · Cited by 379
Characterization of Kiss1 neurons using transgenic mouse models
Cravo, R. M., Margatho, L. O., Osborne-Lawrence, S., Donato, J., Atkin, S., Bookout, A. L., Rovinsky, S., Frazão, R., Lee, C. E., Gautron, L., et al. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2010.11.022 · Cited by 353
Caraty, A., Smith, J. T., Lomet, D., Ben Saïd, S., Morrissey, A., Cognie, J., Doughton, B., Baril, G., Briant, C., & Clarke, I. J. (2007) · Endocrinology · doi:10.1210/en.2007-0554 · Cited by 313
The neurobiology of preovulatory and estradiol-induced gonadotropin-releasing hormone surges
Christian, C. A., & Moenter, S. M. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0023 · Cited by 300
Burke, M. C., Letts, P. A., Krajewski, S. J., & Rance, N. E. (2006) · Journal of Comparative Neurology · doi:10.1002/cne.21086 · Cited by 280
NAKAI, Y., PLANT, T. M., HESS, D. L., KEOGH, E. J., & KNOBIL, E. (1978) · Endocrinology · doi:10.1210/endo-102-4-1008 · Cited by 279
Keen, K. L., Wegner, F. H., Bloom, S. R., Ghatei, M. A., & Terasawa, E. (2008) · Endocrinology · doi:10.1210/en.2008-0231 · Cited by 273
Ramaswamy, S., Seminara, S. B., Ali, B., Ciofi, P., Amin, N. A., & Plant, T. M. (2010) · Endocrinology · doi:10.1210/en.2010-0223 · Cited by 267
Navarro, V. M., Gottsch, M. L., Wu, M., García-Galiano, D., Hobbs, S. J., Bosch, M. A., Pinilla, L., Clifton, D. K., Dearth, A., Ronnekleiv, O. K., et al. (2011) · Endocrinology · doi:10.1210/en.2011-1143 · Cited by 254
Self-citationRance, N. E. (2009) · Peptides · doi:10.1016/j.peptides.2008.05.016 · Cited by 237
Neurokinin B and the hypothalamic regulation of reproduction
Rance, N. E., Krajewski, S. J., Smith, M. A., Cholanian, M., & Dacks, P. A. (2010) · Brain Research · doi:10.1016/j.brainres.2010.08.059 · Cited by 203 · cited 11×
“Although the roles of NKB and other tachykinins in the regulation of gonadotropin secretion had been previously addressed in various species (200, 367, 389), interest on the participation of NKB and NK3R in the control of the HPG axis has grown considerably recently, due mainly to two almost coincident findings: 1) th…”
BackgroundResultInfluentialKinsey‐Jones, J. S., Li, X. F., Knox, A. M. I., Wilkinson, E. S., Zhu, X. L., Chaudhary, A. A., Milligan, S. R., Lightman, S. L., & O’Byrne, K. T. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01807.x · Cited by 196
Robertson, J. L., Clifton, D. K., de la Iglesia, H. O., Steiner, R. A., & Kauffman, A. S. (2009) · Endocrinology · doi:10.1210/en.2009-0247 · Cited by 189
PLANT, T. M., KREY, L. C., MOOSSY, J., McCORMACK, J. T., HESS, D. L., & KNOBIL, E. (1978) · Endocrinology · doi:10.1210/endo-102-1-52 · Cited by 183 · cited 1×
“These observations seemed in agreement with the contention that, in contrast to rodents, the mechanisms for the generation of positive feedback and preovulatory gonadotropin surges in primates appear to reside within the ARC/infundibular nucleus (222, 347).”
ResultWilliams, W. P., Jarjisian, S. G., Mikkelsen, J. D., & Kriegsfeld, L. J. (2011) · Endocrinology · doi:10.1210/en.2010-0943 · Cited by 181
Tenenbaum-Rakover, Y., Commenges-Ducos, M., Iovane, A., Aumas, C., Admoni, O., & de Roux, N. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2147 · Cited by 169
Vida, B., Deli, L., Hrabovszky, E., Kalamatianos, T., Caraty, A., Coen, C. W., Liposits, Z., & Kalló, I. (2010) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02045.x · Cited by 156
Shaw, N. D., Histed, S. N., Srouji, S. S., Yang, J., Lee, H., & Hall, J. E. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2108 · Cited by 149
KiSS-1 and Reproduction: Focus on Its Role in the Metabolic Regulation of Fertility
Tena-Sempere, M. (2006) · Neuroendocrinology · doi:10.1159/000095549 · Cited by 132
Self-citationKokay, I. C., Petersen, S. L., & Grattan, D. R. (2011) · Endocrinology · doi:10.1210/en.2010-0668 · Cited by 131
PLANT, T. M. (1985) · Endocrinology · doi:10.1210/endo-116-4-1341 · Cited by 128
Foradori, C. D., Goodman, R. L., Adams, V. L., Valent, M., & Lehman, M. N. (2005) · Endocrinology · doi:10.1210/en.2004-1326 · Cited by 123
Kisspeptin resets the hypothalamic GnRH clock in men
Chan, Y.-M., Butler, J. P., Pinnell, N. E., Pralong, F. P., Crowley, W. F., Ren, C., Chan, K. K., & Seminara, S. B. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-3046 · Cited by 114
Energy balance and puberty onset: Emerging role of central mTOR signaling
Roa, J., & Tena-Sempere, M. (2010) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2010.05.003 · Cited by 106 · cited 5×
“[Adapted from Roa and Tena-Sempere (377).]”
BackgroundMethodInfluentialKisspeptin regulates prolactin release through hypothalamic dopaminergic neurons
Szawka, R. E., Ribeiro, A. B., Leite, C. M., Helena, C. V. V., Franci, C. R., Anderson, G. M., Hoffman, G. E., & Anselmo-Franci, J. A. (2010) · Endocrinology · doi:10.1210/en.2009-1414 · Cited by 97
Kadokawa, H., Suzuki, S., & Hashizume, T. (2008) · Animal Reproduction Science · doi:10.1016/j.anireprosci.2007.11.005 · Cited by 91
Wacker, J. L., Feller, D. B., Tang, X.-B., DeFino, M. C., Namkung, Y., Lyssand, J. S., Mhyre, A. J., Tan, X., Jensen, J. B., & Hague, C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805251200 · Cited by 71 · cited 2×
“Nonetheless, the importance of the second intracellular loop for proper GPR54 signaling had been previously unveiled by the observation that a point L148S mutation in this region causes iHH in humans (401), and severely blunts ( 90% reduction) the ability of GPR54 to induce PI hydrolysis and to activate ERK1/2 upon Kp…”
BackgroundKisspeptin antagonists: Unraveling the role of kisspeptin in reproductive physiology
Millar, R. P., Roseweir, A. K., Tello, J. A., Anderson, R. A., George, J. T., Morgan, K., & Pawson, A. J. (2010) · Brain Research · doi:10.1016/j.brainres.2010.09.044 · Cited by 69
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Asarian, L., & Geary, N. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00446.2012 · Cited by 513
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Metadata
- Authors
- Pinilla, L., Aguilar, E., Dieguez, C., Millar, R. P., & Tena-Sempere, M.
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2012-07
- Volume
- 92
- Issue
- 3
- Pages
- 1235-1316
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2130784408
- Cited by
- 801
- References
- 56
- FWCI
- 7.82
- Type
- journal article
- Language
- en
- Open access
- green
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