Inherited disorders of GnRH and gonadotropin receptors

Gonadotropin and GnRH receptors belong to the family of G protein coupled r eceptors. Gain of function mutations have been described, yielding constitu tively active receptors. In the case oi the LH receptor these dominant muta tions determine familial male limited precocious puberty. Somatic mutations of this receptor mag. in some cases provoke Leydig-cell adenomas. The cons titutive: LH receptor is not associated with female precocious puberty, ina ctivating mutations are recessive. Alterations in the GnRH receptor determi ne: hypogonadotropic hypogonadism. The clinical diagnosis of this etiology of hypogonadism is extremely difficult. especially in sporadic cases. Mutat ions of gonadotropin receptors determine primary amenorrhea in girls, where as in boys they are responsible fur Leydig cell aplasia or hypoplasia (LH r eceptor) or of a variable alteration of spermatogenesis (FSH receptor). Mut ations provoking only partial alterations of receptor functions;are relativ ely more frequent, than those inducing complete receptor in;inactivity. The y provide interesting insights into the physiology of GnRH and gonadotropin action. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.