The gonadotropin-releasing hormone receptor (GNRHR), also known as the luteinizing hormone releasing hormone receptor (LHRHR), is a member of the seven-transmembrane, G-protein coupled receptor (GPCR) family. It is expressed on the surface of pituitary gonadotrope cells as well as lymphocytes, breast, ovary, and prostate.
This receptor is a 60 kDaG protein-coupled receptor and resides primarily in the pituitary and is responsible for eliciting the actions of LHRH after its release from the hypothalamus.[1] Upon activation, the LHRHr stimulates tyrosine phosphatase and elicits the release of LH from the pituitary.
Evidence exists showing the presence of LHRH and its receptor in extrapituitary tissues as well as a role in progression of some cancers.[2]
There are two major forms of the GNRHR, each encoded by a separate receptor (GNRHR, GNRHR2).[3][4]
Alternative splicing of the GNRHR gene, GNRHR, results in multiple transcript variants encoding different isoforms. More than 18 transcription initiation sites in the 5' region and multiple polyA signals in the 3' region have been identified for GNRHR.
Regulation
The GNRHR responds to GNRH as well as to synthetic GNRH agonists. Agonists stimulate the receptor, however prolonged exposure leads to a downregulation effect resulting in hypogonadism, an effect that is often medically utilized. GNRH antagonists block the receptor and inhibit gonadotropin release. GNRHRs are further regulated by the presence of sex hormones, inhibin, and activin.
Clinical implications
Defects in the GNRHR are a cause of hypogonadotropic hypogonadism (HH).[5]
References
^ Millar RP (2005). "GnRHs and GnRH receptors". Anim. Reprod. Sci.88 (1-2): 5–28. doi:10.1016/j.anireprosci.2005.05.032. PMID 16140177.
^ Harrison GS, Wierman ME, Nett TM, Glode LM (2004). "Gonadotropin-releasing hormone and its receptor in normal and malignant cells". Endocr. Relat. Cancer11 (4): 725–48. doi:10.1677/erc.1.00777. PMID 15613448.
^ Cheng CK, Leung PC (2005). "Molecular biology of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and their receptors in humans". Endocr. Rev.26 (2): 283–306. doi:10.1210/er.2003-0039. PMID 15561800.
