[Inactivating and activating mutations of the human LH/hCG receptor leading to male pseudohermaphroditism and familial male-limited precocious puberty]

Abstract

The human luteinizing hormone/chorionic gonadotropin receptor(LHR) plays an important role in normal reproductive function in humans. Binding of LH to the LHR triggers production of intracellular c-AMP resulting in transcriptional activation of LH responsive genes. Mutations of the human LHR receptor lead to the development of three clinical conditions, namely, Leydig cell hypoplasia, hypergonadotropic hypogonadism and primary amenorrhea, and familial male-limited precocious puberty(FMPP). These mutations cause the receptor to lose its signal transduction activity in the first two conditions and to gain constitutive activity in the third condition. Leydig cell hypoplasia is an autosomal recessive disorder leading to male under-virilization. FMPP is an autosomal dominant disorder, characterized by excessive secretion of testosterone by Leydig cells and pubertal development at a very young age. Sporadic cases are also reported.