Effects of the administration of androgenic and estrogenic steroids on 3α-hydroxysteroid dehydrogenase levels of the intact and castrated dog prostate

The 3α-hydroxysteroid dehydrogenase activity of dog prostate microsomes has been measured by monitoring the NADH-dependent reduction of dihydrotestosterone (17β-hydroxy-5α-androstan-3-one) to 5α-androstane-3α,17β-diol by a novel and highly sensitive enzymatic procedure. In confirmation of the work of others (e.g. G. H. Jacobi, R. J. Moore and J. D. Wilson, Endocrinology 102 (1978) 1748-1755) we have found that 3α-hydroxysteroid dehydrogenase falls to negligible levels after castration. Treatment with estradiol-17β has no effect on the low enzyme activity found in prostate microsomes of castrated dogs, but reduces this activity in intact animals to less than 10% of control values. The specific activities of 3α-hydroxysteroid dehydrogenase of castrated dogs can be restored to 50-100% of control levels by treatment with testosterone, dihydrotestosterone or 5α-androstane-3α,17β-diol. These androgen-induced elevations of the enzyme are antagonized by the simultaneous administration of estradiol-17β. Contrary to the findings of others (G. H. Jacobi and J. D. Wilson, Endocrinology 99 (1976) 602-610) we could detect no correlation between the specific activities of 3α-hydroxysteroid dehydrogenase of prostate microsomes and the age of the animals, the size of their prostates or the presence of hyperplastic disease. In castrated beagles who have developed glandular prostatic hyperplasia in response to repetitive treatment with estradiol-17β in combination with either dihydrotestosterone or 5α-androstane-3α,17β-diol, the 3α-hydroxysteroid dehydrogenase specific activities are 26 and 44% respectively, of untreated controls. Although the capacity of dihydrotestosterone and 5α-androstane-3α,17β-diol to induce prostatic hyperplasia appears to be related to the ability of these steroids to elevate prostatic dihydrotestosterone levels (and the diol is more effective than dihydrotestosterone in doing so), the experimental production of this disease does not appear to require the presence of supernormal levels of 3α-hydroxysteroid dehydrogenase. Similarly, prostatic growth induced by treatment of intact beagles with the three above-mentioned androgens is not associated with elevations of 3α-hydroxysteroid dehydrogenase above normal.