Inhibition of fetal adrenal 21-hydroxylase by naturally occurring steroids.
Inhibitory effects of naturally occurring steroids on 21-hydroxylase activity were determined by measuring the initial conversion rate of 17-hydroxyprogesterone (17alpha-hydroxy-4-pregnene-3, 20-dione) to 11-deoxycortisol (17alpha, 21-dihydroxy-4-pregnene-3, 20-dione) in incubation experiments with the microsomal fraction (10,000--105,000 X g percipitate) of the human fetal adrenal gland. The apparent Michaelis constant (Km) for conversion of 17-hydroxyprogesterone was 13.3 X 10(-6)M. Human fetal adrenal 21-hydroxylase was inhibited by some of the steroids produced in the feto-placental unit. The following steroids acted as competitive inhibitors of the reaction; progesterone (Ki = 20.0 X 10(-6)M), 11-deoxycortisol (Ki = 87.5 X 10(-6)M) and estradiol-17beta (Ki = 87.5 X 10(-6)M). The most potent inhibitor among the estrogens was estradiol-17beta.
D000311:Adrenal Glands / Q000196:embryology / Q000201:enzymology*; D003900:Desoxycorticosterone / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000201:enzymology*; D006801:Humans; D006908:Hydroxyprogesterones / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*
D006908:Hydroxyprogesterones; D003900:Desoxycorticosterone; D011374:Progesterone; D004958:Estradiol; D006899:Mixed Function Oxygenases