5alpha-reductase-2 deficiency and complete androgen insensitivity: lessons from nature.

Abstract

The importance of the hormones testosterone and dihydrotestosterone in the male is best illustrated by studies of the inherited condition of male pseudohermaphroditism due to 5a—reductase-2 deficiency (Imperato-McGinley et al, 1974,1976;Fratianni and Imperato-McGInley, 1994; Walsh et al, 1974). Testosterone is converted to dihydrotestosterone by two known 5a—reductase isoenzymes 5a—reductase-1 and 5a—reductase-2. It is defects in the 5a—recluctase-2 gene that cause male pseudohermaphroditism. The syndrome of 5a-reductase-2 deficiency results in a selective decrease in dihydrotestosterone. The clinical and laboratory findings of this syndrome have defined specific roles for testosterone and dihydrotestosterone in male sexual differentiation and development. The unusual psychosexual aspects of this clinical entity have helped to define the role of androgens in gender identity formation.