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.
Department of Chemistry, South Central Institute for National Minorities, Wuhan, PRC.
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Huang
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Kominami
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Takemori
D019326:17-alpha-Hydroxyprogesterone; D004092:20-alpha-Dihydroprogesterone / Q000494:pharmacology*; D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology*; D000735:Androstenedione / Q000378:metabolism*; D000818:Animals; D003350:Cortodoxone / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology; D006168:Guinea Pigs; D006900:Hydroxylation / Q000187:drug effects; D006908:Hydroxyprogesterones / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D011374:Progesterone / Q000378:metabolism
D006908:Hydroxyprogesterones; D004092:20-alpha-Dihydroprogesterone; D000735:Androstenedione; D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone; D003577:Cytochrome P-450 Enzyme System; D003350:Cortodoxone