SUMMARY The Luteinizing hormone/chorionic gonadotropin receptor (LHR) plays a critical role in human male sexual development. Both gain-of-function and loss-of-function mutations of the LHR have been described. Gain-of-function mutations are dominant and cause constitutive activation of the receptor resulting in familial male-limited precocious puberty (FMPP). All activating mutations are single point mutations and are located in the transmembrane domain (TM). TM helix Ⅵ harbors the largest number of activating mutations with the codon of Asp-578 being the hot-spot of mutation. Besides causing abnormal sexual development, constitutively activated LHR may predispose an individual to the development of testicular neoplasia. The anti-thesis of FMPP is Leydig cell hypoplasia (LCH). This is caused by mutations that inactivate the LHR resulting in subnormal male sexual development or male pseudohermaphroditism. Inactivating mutations are recessive. The genetic cause of LCH is variable and there is no mutation hot-spot. Genotype-phenotype correlation can be identified in LCH with the milder form caused by mutated LHR with residual activity and the severe form caused by absence of signal transduction activity of the mutated receptor. Molecular diagnosis of the disorders caused by mutation of the LHR can be achieved by direct sequencing of the LHR gene.

The Luteinizing hormone/chorionic gonadotropin receptor (LHR) plays a critical role in human male sexual development. Both gain-of-function and loss-of-function mutations of the LHR have been described. Gain-of-function mutations are dominant and cause constitutive activation of the receptor resulting in familial male-limited precocious puberty (FMPP). All activating mutations are single point mutations and are located in the transmembrane domain (TM). TM helix Ⅵ harbors the largest number of activating mutations with the codon of Asp-578 being the hot-spot of mutation. Besides causing abnormal sexual development, constitutively activated LHR may predispose an individual to the development of testicular neoplasia. The anti-thesis of FMPP is Leydig cell hypoplasia (LCH). This is caused by mutations that inactivate the LHR resulting in subnormal male sexual development or male pseudohermaphroditism. Inactivating mutations are recessive. The genetic cause of LCH is variable and there is no mutation hot-spot. Genotype-phenotype correlation can be identified in LCH with the milder form caused by mutated LHR with residual activity and the severe form caused by absence of signal transduction activity of the mutated receptor. Molecular diagnosis of the disorders caused by mutation of the LHR can be achieved by direct sequencing of the LHR gene.