In vitro effect of 16alpha-hydroxyprogesterone on the enzyme activities related to androgen production in human testes.
Progesterone was converted in vitro to 16alpha- and 17alpha-hydroxyprogesterones in the presence of NADPH by the testicular microsomal fraction (precipitate at 10 000 x g-105 000 x g) obtained from patients with prostatic carcinoma. 16alpha-Hydroxyprogesterone was not metabolized by either the microsomal or the cytosol fractions, and accumulated in the incubation medium. 16alpha-Hydroxyprogesterone competitively inhibited the activity of the C-17-C-20 lyase in the testicular microsomal fraction with an estimated inhibitor constant of 72 micron. Moreover, the 16alpha-hydroxyprogesterone non-competitively inhibited the activity of the 20alpha-hydroxysteroid dehydrogenase in the testicular cytosol fraction and had an estimated inhibitor constant of 52.9 micron. Other testicular enzymes related to steroid metabolism, such as delta5-3beta-hydroxysteroid dehydrogenase coupled with the delta4-delta5 isomerase, 16alpha-hydroxylase, 17alpha-hydroxylase, and 17beta-hydroxysteroid dehydrogenase were not influenced in vitro by 16alpha-hydroxyprogesterone at the concentration of 0.1 mM. From these findings, it is concluded that 16alpha-hydroxyprogesterone inhibit specifically the cleavage of the side-chain of 17alpha-hydroxypregnenes in the course of androgen formation from pregnenolone in vitro.
D000728:Androgens / Q000096:biosynthesis*; D001189:Aryl Hydrocarbon Hydroxylases; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D006908:Hydroxyprogesterones / Q000378:metabolism / Q000494:pharmacology*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D008190:Lyases / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism; D013251:Steroid Isomerases / Q000378:metabolism; D013737:Testis / Q000201:enzymology*
D000728:Androgens; D006908:Hydroxyprogesterones; D011374:Progesterone; D010088:Oxidoreductases; D006913:Hydroxysteroid Dehydrogenases; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D039181:Steroid 16-alpha-Hydroxylase; D008190:Lyases; D013251:Steroid Isomerases