ABSTRACT
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.
KEYWORDS
LH receptor - precocious puberty - pseudohermaphroditism - Leydig cell hypoplasia
