Prevention of Anatomic Defects in Congenital Adrenal Hyperplasia Produced by Estradiol-17 β in Rats

The production of hypospadias, clitoral hypertrophy and adrenal hyperplasia with deficient activity of 3β-hydroxysteroid dehydrogenase by large doses of estradiol-17β (similar to the production of these defects by a C-19 substrate analog) has suggested that these fetal effects of estradiol-17β are due to inhibition of fetal testicular synthesis of testosterone or testosterone-like steroids, and of adrenal synthesis of corticosterone at the level of this enzyme. This hypothesis was tested by determining the effects of testosterone or corticosterone administered to pregnant females treated with estradiol-17β from the 15th to 20th days of gestation. In the mothers, testosterone did not affect either the marked adrenal and ovarian hyperplasia, or the reduced specific activity of the dehydrogenase in these glands produced by estradiol-17β, while corticosterone reduced only the adrenal hyperplasia produced by this estrogen. In the male fetus, testosterone reduced the production of hypospadias by estradiol-17β, whereas corticosterone prevented the adrenal hyperplasia and the changes in the external genitalia of female fetuses produced by estradiol-17β. The experiments provide further data consistent with the previous suggestion that the paradoxic effects of estradiol-17β on fetal genital differentiation are due to inhibition of the fetal dehydrogenase system.