IN VITRO EFFECT OF 16α-HYDROXYPROGESTERONE ON THE ENZYME ACTIVITIES RELATED TO ANDROGEN PRODUCTION IN HUMAN TESTES

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Abstract
Progesterone was converted in vitro to 16.alpha.- and 17.alpha.-hydroxyprogesterones in the presence of NADPH by the testicular microsomal fraction (precipitate at 10,000 .times. g-105,000 .times. g) obtained from patients with prostatic carcinoma. 16.alpha.-Hydroxyprogesterone was not metabolized by either the microsomal or the cytosol fractions, and accumulated in the incubation medium. 16.alpha.-Hydroxyprogesterone competitively inhibited the activity of the C-17-C-20 lyase in the testicular microsomal fraction with an estimated inhibitor constant of 72 .mu.M. Moreover, the 16.alpha.-hydroxyprogesterone non-competitively inhibited the activity of the 20.alpha.-hydroxysteroid dehydrogenase in the testicular cytosol fraction and had an estimated inhibitor constant of 52.9 .mu.M. Other testicular enzymes related to steroid metabolism, such as .DELTA.5-3.beta.-hydroxysteroid dehydrogenase coupled with the .DELTA.4-.DELTA.5 isomerase, 16.alpha.-hydroxylase, 17.alpha.-hydroxylase and 17.beta.-hydroxysteroid dehydrogenase were not influenced in vitro by 16.alpha.-hydroxyprogesterone at the concentration of 0.1 mM. 16.alpha.-Hydroxyprogesterone may inhibit specifically the cleavage of the side-chain of 17.alpha.-hydroxypregnenes in the course of androgen formation from pregnenolone in vitro.