Gonadotropin-releasing hormone receptor

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 kDa G protein-coupled receptor and resides primarily in the pituitary and is responsible for eliciting the actions of LHRH after its release from the hypothalamus. 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.

Function
Following binding of Gonadotropin releasing hormone (GNRH), GNRHR associates with G-proteins that activate a phosphatidylinositol (PtdIns)-calcium second messenger system. Activation of GNRHR ultimately causes the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH).

Gene
There are two major forms of the GNRHR, each encoded by a separate receptor.

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).