title: [GnRH resistance and the GPR54 gene].
abstract: Current data make it possible to relate idiopathic hypogonadotrophic hypogonadism to mutations affecting the GnRH I-1 receptor and also to new "loss-of-function" mutations concerning another receptor, GPR54. It now seems that mutations of the pituitary GnRH receptor are not the only explanation of most cases of sporadic isolated hypogonadotrophic hypogonadism, and, on the contrary, there are certain familial forms, where no mutation has been demonstrated, suggesting the potential involvement of other genes. The role of another G protein-coupled glycoprotein membrane receptor, GRP54, already known for its involvement as a metastasis suppressor, has been demonstrated. Bioclinical studies of families affected with the disorder by pheno/genotypic correlation demonstrated that "loss-of-function" mutations affecting the GPR54 gene coding for GRP54 are the cause of hypogonadotrophic hypogonadism. GPR54 therefore appears to be involved at hypothalamic and pituitary level. It is not involved in sexual differentiation, but may modulate GnRH secretion or affect its pituitary response. Further investigations are required to determine the levels of action of this receptor which may provide a new pharmacological target in the future.
authors.affiliation: Service de génétique moléculaire, pharmacogénétique et hormonologie, hôpital de Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France. Nicolas.deroux@bct.ap-hop-paris.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: de Roux
mesh_terms: D002462:Cell Membrane / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007006:Hypogonadism / Q000235:genetics / Q000503:physiopathology; D007031:Hypothalamus / Q000502:physiology; D010902:Pituitary Gland / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D000074502:Receptors, Kisspeptin-1; D011966:Receptors, LHRH / Q000502:physiology; D018013:Receptors, Neuropeptide / Q000235:genetics* / Q000502:physiology; D012733:Sex Differentiation
chemical_list: C484844:GNRHR protein, human; C118688:KISS1R protein, human; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D011966:Receptors, LHRH; D018013:Receptors, Neuropeptide; D007987:Gonadotropin-Releasing Hormone; D019204:GTP-Binding Proteins