Inhibitory effect on delta 5-3 beta-hydroxysteroid dehydrogenase, delta 4-delta 5-isomerase and 17 alpha-hydroxylase activities of pig adrenal microsomes by various inhibitors of steroid metabolizing enzyme and steroids

Abstract

By the kinetic analysis of pig adrenal Δ5-3β-hydroxysteroid dehydrogenase and Δ4-Δ5-isomerase activities, the apparent Km values of pregnenolone, 17α-hydroxypregnenolone and dehydroepiandrosterone for the dehydrogenase activity were identified to be 1.2, 1.8 and 0.2μM (Vmax: 23, 26 and 26nmol/min/mg Protein); those of pregn-5-ene-3, 20-dione and androst-5-ene-3, 17-dione for the isomerase activity were 9.1 and 22μM (Vmax: 220 and 270 nmol/min/mg protein), respectively.The inhibitory effect by various inhibitors of steroid metabolizing enzyme and steroids on the dehydrogenase activity and the 17α-hydroxylase activity were investigated using pregnenolone as substrate. The dehydrogenase activity was considerably inhibited by cyanoketone, SU 8000, o, P'DDD and SKF 525A. On the other hand, the hydroxylase activity was inhibited by SU 8000, SU 10603, cyanoketone, o, P'DDD and SKF 525A. Furthermore, various kinds of steroid, androgens, corticoids, estrogens, etc., inhibited the dehydrogenase activity. However, the hydroxylase activity was not inhibited by ail of those steroids except 5α-dihydrotestosterone and 20α-or 20β-hydroxyprogesterone.