[Constitutively activating mutations in the luteinizing hormone receptor gene in cases of male-limited precocious puberty]

Abstract

Familial male-limited precocious puberty(FMPP) is an autosomal dominant disorder characterized by marked elevation of serum testosterone despite low levels of gonadotropin. In 1993, a single point mutation, Asp578 to Gly(D578G), in the luteinizing hormone(LH) receptor gene was found in FMPP families. After discovery of the D578G mutation in the sixth transmembrane region of the LH receptor gene, seven other mutations in the fifth and sixth transmembrane regions, two mutations in the third intracellular loop and one mutation in the second transmembrane domain of the LH receptor have been found in the patients with familial and sporadic male-limited precocious puberty. These mutations caused constitutively elevated cAMP levels in transfected cells in vitro. These results suggested that Leydig cell activation and precocious puberty were caused by activating mutations of the LH receptor.