Persistent Postpubertal Elevation of Activity of Steroid 5α-Reductase in the Adrenal of Rat Pseudohermaphrodites and Correction by Large Doses of Testosterone or DHT

The development of adrenal androgen metabolizing enzymes with androstenedione and testosterone as substrates has been studied in the rat pseudohermaphrodite and its King-X Holtzman male littermates and females. Enzymatic activity has been determined by the separation and quantitation of the products formed from the labeled androgen substrates by a partition system on thin-layer chromatography, and by trimethylsilylether derivative formation and radio-gas-liquid chromatography. The separations have been confirmed by recrystallization. Serum corticosterone is significantly higher in the pseudohermaphrodite than in males or females indicating intact corticoidogenic enzymes. The development of adrenal androgen metabolizing enzymes in the pseudohermaphrodite differs from that of its littermate male primarily by a persistent postpubertal elevation of activity of 5α-reductase and a failure of a postpubertal rise in 17-ketoreductase, the enzyme converting the 17-ketone of androstenedione to the 17β-alcohol of testosterone. Development of activity of the enzyme converting the 17β-alcohol of testosterone to the 17-ketone, 17β-hydroxysteroid oxidoreductase, does not differ in the 2 animals, but differs from that of 17-ketoreductase. Postpubertal administration of large doses of androgens corrects the persistently elevated levels of 5α-reductase, as well as the depressed levels of the 17-ketoreductase in the pseudohermaphrodite to normal male values. The development of these adrenal defects and the correction by postpubertal (but not by prepubertal) testosterone and dihydrotestosterone in the pseudohermaphrodite also occurs in prepubertally orchiectomized genetic male rats. Thus, the present findings suggest that the development of the mechanisms controlling adrenal steroid metabolizing enzymes in the pseudohermaphrodite is similar to that of the castrated rat. (Endocrinology94: 1232, 1974)