5 alpha-reductase deficiency: human and animal models.

The syndrome of male pseudohermaphroditism secondary to 5 alpha-reductase deficiency is reviewed, as are hormonal evaluation and tissue studies documenting the enzyme deficiency. These studies reveal that the 5 alpha-metabolite dihydrotestosterone is essential for differentiation of the external genitalia and prostate. Studies of male rat fetuses treated with 5 alpha-reductase inhibitors during the critical period of sexual differentiation in utero reveal incomplete masculinization of the external genitalia and impaired prostate growth and development. Thus, conclusive evidence is provided for the hypothesis that 5 alpha-reductase activity and dihydrotestosterone formation are essential for normal differentiation of the male external genitalia and the prostate.