Spectrum of activation and inactivation of gene for the luteinizing hormone chorionic gonadotrophin receptor

The LHCGR gene codes for the receptor protein called the luteinizing hormone/chorionic gonadotropin receptor (LHCGR). In the receptor sites of LHCGR two specific hormonal ligands initiate the signal which affect cell development and function. One of the ligands human chorionic gonadotropin (HCG) stimulates the development of Leydig cells and hence androgen production in 46,XY in early fetal life. The second ligand LH triggers the cells to produce androgens. Both loss and gain of function mutations of the LHCGR gene can cause human diseases. In a case of an autosomal recessive inactivation mutation of LHCGR leads to Leydig cell hypoplasia and affects normal male sexual development and reproduction. Severe inactivating mutations lead to Leydig cell hypoplasia type 1, with the absence of Leydig cells on histological sections was the key to the diagnosis. Leydig cell hypoplasia type 2 is due to a partial inactivating mutation in the LHCGR gene, which could present in a phenotypic male as micropenis, hypospadias to several degrees of undervirilization of 46,XY male. In case of an autosomal dominant or de novo activating mutation of the LHCGR results in the constitutive activation and presenting in male as testotoxicosis, or familial male-limited precocious puberty (FMPP), which is a rare gonadotropin-independent form of precocious puberty. In the second part of the chapter is review on presentation, medical therapy with aromatase inhibitors and androgen receptor blockers and very rarely the use of surgical therapy.