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It is a member of the seven-transmembrane, G-protein coupled receptor (GPCR) family and is activated by the peptide hormone gonadotropin-releasing hormone (GnRH) or the synthetic agonist. The GnRHR is expressed on the surface of pituitary gonadotrope cells as well as lymphocytes, breast, ovary, and prostate ^[1]. Its activity is critical for successful reproductive function. Several diseases are associated with a dysfunction of this receptor or the corresponding signaling cascade.

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Biological Function

The gonadotropin releasing hormone 1 receptor is located in the plasmic membrane of pituitary gonadotrope cells in the anterior pituitary, a major organ of the endocrine system in the brain. It is activated by the gonadotropin releasing hormone (GnRH) which acts upon GnRHRs as the key regulator of puberty and reproduction. This peptide hormone is produced in the hypothalamus but gets secreted and acts upon GnRHRs in the anterior pituitary to exert its effects on reproductive maturation. The activation of the receptor, associates with G-proteins, leads to the releasing of gonadotropic luteinizing hormone (LH) and follicle stimulating hormone (FSH) by activating several signaling cascades. These pathways mainly corresponds to the inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG), MAPK, and adenyl cyclase pathways. ^[4]

Disease

A mutation or a dysfonctionnement of the receptor could cause diseases impacting the reproduction function. More generally, the dysfonctionnement of the pathways involving GnRH and its receptor leads to endocrine pathologies called hypogonadisms. ^[5] It exits many types of hypogonadism but the one involving the mutation of the receptor is the idiopatic hypogonadotropic hypogonadism (IHH). In this case, the mutation leads to failure of detectable ligand binding causing the decreased efficiency of the inisitol pathway and consequently leading to the decrease of the LH, FSH, and sex steroid secretions ^[6].

Relevance

One of the main using of the couple GnRH - GnRHR in the medicine field is for fertility preservation as an alternative of cryopreservation ^[7].

Structural highlights

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