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.