LH receptor defects.

In this article the role of LH receptor gene mutations in patients with aberrant sex differentiation is discussed. In a dominant autosomal familial form of precocious puberty in boys (familial male-limited precocious puberty) LH receptor gene mutations have been identified. These single amino acid changes, mostly found in the sixth transmembrane helix and the third intracellular loop of the transmembrane domain of the LH receptor, cause constitutive activation of LH receptor protein without the hormone present, resulting in precocious production of testosterone by the testicular Leydig cells. The large number of activating LH receptor mutations have allowed more precise molecular modeling of the LH receptor protein. In a rare hereditary form of 46,XY male pseudohermaphroditism known as Leydig cell hypoplasia, LH receptor gene mutations have been identified that completely or partially inactivate the LH receptor protein. Large gene deletions cause complete absence of the LH receptor protein, whereas other, more subtle missense mutations prevent the receptor from assuming an active conformation.