Thegonadotropin-releasing hormone receptor (GnRHR), also known as theluteinizing hormone releasing hormone receptor (LHRHR), is a member of the seven-transmembrane,G-protein coupled receptor (GPCR) family. It is the receptor ofgonadotropin-releasing hormone (GnRH). Agonist binding to the GnRH receptor activates the Gq/11 family of heterotrimeric G proteins.^[1] The GnRHR is expressed on the surface ofpituitary gonadotrope cells as well aslymphocytes,breast,ovary, andprostate.

This receptor is a 60kDaG protein-coupled receptor and resides primarily in thepituitary and is responsible for eliciting the actions of GnRH after its release from thehypothalamus.^[2] Upon activation, the LHRHr stimulatestyrosine phosphatase and elicits the release of LH from the pituitary.

Evidence exists showing the presence of GnRH and its receptor in extrapituitary tissues as well as a role in progression of somecancers.^[3]

Following binding of GnRH, the GnRHR associates with G-proteins that activate aphosphatidylinositol (PtdIns)-calciumsecond messenger system. Activation of the GnRHR ultimately causes the release offollicle stimulating hormone (FSH) andluteinizing hormone (LH).

There are two major forms of the GNRHR, each encoded by a separate gene (GNRHR andGNRHR2).^[4][5]

Alternative splicing of the GNRHR gene,GNRHR, results in multipletranscript variants encoding differentisoforms. More than 18transcription initiation sites in the 5' region and multiplepolyA signals in the 3' region have been identified forGNRHR.

The GnRHR responds to GnRH as well as to syntheticGnRH agonists. Agonists stimulate the receptor, however prolonged exposure leads to adownregulation 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 ofsex hormones as well asactivin and inhibin.

• Azagly-nafarelin
• Buserelin
• Deslorelin
• Fertirelin
• GnRH
• Gonadorelin
• Goserelin
• Histrelin
• Lecirelin
• Leuprorelin
• Nafarelin
• Peforelin
• Triptorelin

• Abarelix
• Cetrorelix
• Degarelix
• Ganirelix
• Ozarelix

• Elagolix
• Linzagolix
• Opigolix
• Relugolix
• Sufugolix

Current research is looking into pharmacoperones, or chemical chaparones that promote the shuttling of mature Gonadotropin-releasing hormone receptor (GNRHR) protein to the cell surface, leading to a functional protein. Gonadotropin-releasing hormone receptor function has been shown to be deleteriously effected by point mutations in its gene. Some of these mutations, when expressed, cause the receptor to remain in the cytosol. An approach to rescue receptor function utilizes pharmacoperones or molecular chaperones, which are typically small molecules that rescue misfolded proteins to the cell surface. These interact with the receptor to restore cognate receptor function devoid of antagonist or agonist activity. This approach, when effective, should increase therapeutic reach. Pharmacoperones have been identified that restore function of Gonadotropin-releasing hormone receptor.^[6][7]

Defects in the GnRHR are a cause ofhypogonadotropic hypogonadism (HH).^[8]

Normalpuberty begins between ages 8 and 14 in girls and between 9 and 14 in boys. Puberty, however, for some children can come much sooner (precocious puberty) or much later (delayed puberty). In some cases puberty never occurs and thereby contributes to the estimated 35-70 million infertile couples worldwide.^{[citation needed]} Among children, the abnormally early or late onset of puberty exerts intense emotional and social stress that too often goes untreated.

The timely onset of puberty is regulated by many factors and one factor that is often referred to as the master regulator of puberty and reproduction is GnRH. This peptide hormone is produced in the hypothalamus but gets secreted and acts upon GnRHRs in theanterior pituitary to exert its effects onreproductive maturation.

Understanding how GnRHR functions has been key to developing clinical strategies to treat reproductive-related disorders.^[9][10][11]

• GnRH modulator

• "Gonadotrophin-Releasing Hormone Receptors".IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived fromthe original on 2016-03-03. Retrieved2008-12-04.
• GNRHR+protein,+human at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

• Genes on human chromosome 4
• Genes on human chromosome 1
• G protein-coupled receptors
• Gonadotropin-releasing hormone and gonadotropins

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