Pseudohermaphroditism, Male, Due to 5α-Reductase-2 Deficiency

Abstract

5α-Reductase isozymes convert testosterone to dihydrotestosterone (DHT). There are two 5α-reductase isozymes, type 1 and type 2, in humans. Mutations in the 5α-reductase-2 gene cause male pseudohermaphroditism. The affected 46,XY individuals have high normal to elevated plasma testosterone levels and decreased DHT levels, resulting in elevated testosterone/DHT ratios. They have ambiguous external genitalia at birth and are often raised as girls. Wolffian differentiation, however, occurs normally and the individuals have epididymides, vasa deferentia, and seminal vesicles. Virilization occurs at puberty, frequently accompanied by a gender role change from female to male. The prostate in adulthood is small and rudimentary; facial hair and body hair are absent or decreased. Spermatogenesis can be normal if the testes are descended. Prostate cancer and balding have not been reported. The analyses of 5α-reductase-2-deficient subjects highlight the significance of DHT in male sexual differentiation, physiology, and pathophysiology.