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Gonadotropin Releasing Hormone Receptor Signaling and Functions

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Gonadotropin-releasing hormone (GnRH) is a neuropeptide that plays a central role in vertebrate reproduction. It acts via 7 transmembrane domain Gq protein-coupled receptors in the pituitary gland. GnRH receptor (GnRHR) expression, signaling and roles have been most investigated in the mammalian pituitary ...

Gonadotropin-releasing hormone (GnRH) is a neuropeptide that plays a central role in vertebrate reproduction. It acts via 7 transmembrane domain Gq protein-coupled receptors in the pituitary gland. GnRH receptor (GnRHR) expression, signaling and roles have been most investigated in the mammalian pituitary gonadotrophs. Their activation leads to InsP3-dependent calcium signaling and protein kinase C activation, accompanied with acute regulation of gonadotropin secretion. These receptors also trigger multiple lipid-derived messengers and mitogen-activated protein kinases. The GnRH-induced gene network is very complex and includes transcriptional regulation of gonadotroph signature genes: GnRHR gene, glycoprotein hormone alpha subunit gene, luteinizing hormone beta subunit gene, and follicle-stimulating hormone beta subunit gene. In non-mammalian vertebrates, prolonged activation of GnRHR leads to desensitization and receptor internalization. Mammalian GnRHR lacks a C-terminal tail, which is a cause for loss of receptor desensitization. This peculiarity led to research of GnRHR trafficking and subsequent identification of mutations that are affecting human fertility. In the last decade, GnRH became an important target in assisted reproductive technologies in domestic animals and humans. GnRHR appear early in the evolution of bilaterian animals; their natural ligands are beginning to emerge and their functions are not necessarily related to reproduction. GnRHR and GnRH ligands are also found in extra-pituitary sites, including central nervous system, reproductive tissues, and cancer cells derived from such tissue. The enhanced interest for the extra-pituitary receptors systems comes from the findings that they mediate antiproliferative and/or pro-apoptotic effects and may therefore be directly targeted in cancer therapy. The collection of review articles on these topics should encompass the perspectives we have today regarding GnRH receptor evolution, roles and signaling, and summate recent advances in practical application of this knowledge.


Keywords: GnRHR, cell signaling, gonadotropins, reproduction, fertility


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