Regulation of the activities of 17-hydroxylase and 17,20-desmolase in the human adrenal cortex: kinetic analysis and inhibition by endogenous steroids.

Kinetic analyses of 17-hydroxylase and 17,20-desmolase activities have been performed on human adrenal microsomes from 12 individuals, aged 1-60 yr. The median Michaelis constant of 17-hydroxylase for the substrate pregnenolone was 0.09 microM, and that of 17,20-desmolase for the substrate 17-hydroxypregnenolone was 0.12 microM. The median maximum velocity of 17-hydroxylase (0.25 nmol/mg X min) was significantly greater than that of the desmolase (0.13 nmol/mg X min). There was no significant correlation between the age of the adrenal donor and the Michaelis constant, but the maximum velocity for both activities in the single infant donor was lower than the values in older individuals. The inhibitory effects of various steroids on both enzyme activities also were studied. All steroids examined, except cortisol, competitively inhibited both enzymes. In each case the inhibition constant was higher for 17-hydroxylase than for 17,20-desmolase, indicating that C21 side-chain cleavage would be more sensitive to inhibition by endogenous steroids. The results, taken together with those of similar studies of 3 beta-hydroxysteroid dehydrogenase kinetics, are compatible with the suggestion that increased enzyme synthesis mediated by ACTH and differential inhibition by endogenous steroids may, in part, account for developmental changes in adrenal hormone secretion.