The GPR54 Gene as a Regulator of Puberty

Puberty does not occur in patients with idiopathic hypogonadotropic hypogonadism. This study investigated mutations in a candidate gene encoding a G protein–coupled receptor ( GPR54 ). Affected members of an index pedigree were homozygous for an L148S mutation; an unrelated proband had two separate mutations, R331X and X399R. Isolated hypogonadotropic hypogonadism was also present in a knockout mouse that was engineered to lack this gene. Clues from mutations in a candidate gene. The neuroendocrine and genetic control of sexual maturation at puberty remains one of the great mysteries of human biology. The secretion of gonadotropin-releasing hormone by the hypothalamus represents the first known step in the reproductive cascade — initiating pulsatile release of gonadotropins, gonadal secretion of sex steroids, pubertal development, and gametogenesis. Although the central role of gonadotropin-releasing hormone in the reproductive hierarchy of all mammals is undisputed, little is understood of the genetic factors that modulate its secretion. The identification of such factors is critical for advancing the understanding of normal reproduction and for providing insight into disorders of the . . .