Human Reproduction Update Advance Access originally published online on May 26, 2006
Human Reproduction Update 2006 12(5):631-639; doi:10.1093/humupd/dml023
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GPR54 and kisspeptin in reproduction
Physiology Section, Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain
E-mail: fi1tesem{at}uco.es
Kisspeptins, the peptide products of the KiSS-1 gene, were identified in 2001 as natural ligands of the previously orphan G protein-coupled receptor, GPR54. They include, among others, metastin and kisspeptin-10. The known biological functions of kisspeptins were initially restricted to their ability to suppress tumour metastasis, hence the name of metastin. However, in late 2003, two groups independently reported that loss-of-function mutations of the GPR54 gene are linked to absence of puberty onset and hypogonadotrophic hypogonadism in humans—a phenotype that was reproduced in GPR54-null mice. Those seminal observations revealed a totally unexpected, fundamental role of the KiSS-1/GPR54 system in control of puberty and reproductive function and boosted an extraordinary interest for the characterization of these novel facets of kisspeptin physiology. Indeed, in the last 2 years, metastin and kisspeptin-10 have been demonstrated as very potent stimulators of the gonadotrophic axis, in a number of species and through different routes of administration. In addition, the hypothalamic KiSS-1/GPR54 system has been proven as an essential gatekeeper of GnRH neurons, involved in their activation at puberty and their regulation by gonadal steroids and (probably) metabolic factors. This review comprehensively examines the experimental evidence obtained to date supporting a pivotal role of kisspeptins and GPR54 in the control of reproduction.
Key words: GnRH / gonadotrophins / GPR54 / kisspeptin / puberty
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