Inhibitory effects of 20 alpha-hydroxyprogesterone on steroid hydroxylation reactions of guinea pig adrenal microsomes.

Using guinea pig adrenal microsomes, we studied the inhibitory effects of 20 alpha-hydroxyprogesterone on steroid hydroxylation reactions catalyzed by cytochromes P-450. When 17 alpha-hydroxyprogesterone was used as a substrate, 20 alpha-hydroxyprogesterone functioned as a competitive inhibitor on the C17-C20 bond cleavage reaction of P-450(17)alpha lyase. The inhibition constant, Ki was 1.37 mumol/L. 20 alpha-hydroxyprogesterone also competitively inhibited the conversion of 17 alpha-hydroxyprogesterone to 11-deoxycortisol by the action of P-450c21. The value of Ki was 1.73 mumol/L. When progesterone was used as a substrate, 20 alpha-hydroxyprogesterone inhibited neither the 21-hydroxylation of P-450c21, the C17-C20 bond cleavage, nor 17 alpha-hydroxylation of P-450(17)alpha lyase. Based on these results, we can deduce that the production of androstenedione from progesterone by the action of P-450(17)alpha lyase proceeds through a successive monooxygenase reaction.