GnRHreceptorer

GnRHreceptoren, or the GnRH receptor (GNRHR), is a G protein-coupled receptor that binds gonadotropin-releasing hormone (GnRH). In humans the receptor is encoded by the GNRHR gene, located on chromosome 4. The receptor belongs to the class A rhodopsin-like GPCRs and features seven transmembrane domains.

Binding of GnRH to the receptor on pituitary gonadotrophs activates Gq/11 proteins, triggering phospholipase Cβ activity and the production of inositol trisphosphate and diacylglycerol. This leads to mobilization of intracellular Ca2+ and activation of protein kinase C, ultimately stimulating the synthesis and release of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The GnRH signal is normally pulsatile; continuous GnRH exposure causes receptor desensitization and downregulation, resulting in suppressed LH/FSH secretion.

Expression is highest in the anterior pituitary, where the receptor mediates gonadotropin release. GnRH receptors have also been reported at lower levels in some extra-pituitary tissues and tumors, but the functional relevance varies by context.

Genetic mutations in GNRHR can cause autosomal recessive forms of hypogonadotropic hypogonadism, characterized by reduced LH/FSH production and impaired puberty and fertility; in some cases affected individuals retain normal sense of smell. Clinically, GnRH receptor activity is targeted with hormonal therapies: GnRH agonists (for example, leuprolide, nafarelin) initially stimulate and then downregulate the receptor, and are used in puberty suppression, endometriosis, uterine fibroids, and hormone-dependent cancers; GnRH antagonists (such as cetrorelix, ganirelix) directly block receptor activity and are used to prevent LH surges during assisted reproduction.