Production of congenital adrenal cortical hyperplasia, hypospadias, and clitoral hypertrophy (adrenogenital syndrome) in rats by inactivation of 3-beta-hydroxysteroid dehydrogenase.

Abstract

SummaryVarying daily doses of a steroidal inhibitor of 3β-hydroxysteroid dehydrogenase (2α-cyano-4,4,17α-trimethylandrost-5-en-17β-ol-3-one), were administered to pregnant rats on the 15 th to 20th days of gestation to determine whether this inhibitor could produce the biological manifestations of the human disease associated with deficient activity of this enzyme. A single dose of the inhibitor was also administered to pregnant rats on various days to determine the critical periods for production of these manifestations. Infants with this disorder have hyperplastic adrenal cortices deficient in activity of the 3β-enzyme, incomplete masculine development in males resulting in hypospadias with shortening of the anogenital distance, and clitoral hypertrophy without urethral orificial displacement in females. The experimental fetuses had adrenal cortical hyperplasia (average of 5.9 ± 1.32 mg against 2.2 ± 0.26 mg controls), deficient histochemical activity of the 3β-enzyme in the adrenals and testes, increas...