Inherited disorders of GnRH and gonadotropin receptors.
Gonadotropin and GnRH receptors belong to the family of G protein coupled receptors. Gain of function mutations have been described, yielding constitutively active receptors. In the case of the LH receptor these dominant mutations determine familial male limited precocious puberty. Somatic mutations of this receptor may in some cases provoke Leydig-cell adenomas. The constitutive LH receptor is not associated with female precocious puberty. Inactivating mutations are recessive. Alterations in the GnRH receptor determine hypogonadotropic hypogonadism. The clinical diagnosis of this etiology of hypogonadism is extremely difficult, especially in sporadic cases. Mutations of gonadotropin receptors determine primary amenorrhea in girls, whereas in boys they are responsible for Leydig cell aplasia or hypoplasia (LH receptor) or of a variable alteration of spermatogenesis (FSH receptor). Mutations provoking only partial alterations of receptor functions are relatively more frequent, than those inducing complete receptor inactivity. They provide interesting insights into the physiology of GnRH and gonadotropin action.
de Roux
N
N
INSERM U.135-Hormones, Gènes et Reproduction, Laboratoire d'Hormonologie et de Biologie Moléculaire, Hopital de Bicêtre, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France.
Milgrom
E
E
D005260:Female; D006062:Gonadotropins / Q000378:metabolism*; D006801:Humans; D007006:Hypogonadism / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D009154:Mutation / Q000235:genetics; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism*; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism*; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism*
D006062:Gonadotropins; D011962:Receptors, FSH; D011974:Receptors, LH; D011966:Receptors, LHRH