Relative Inactivation of Steroidogenic Enzyme Activities ofin VitroVitamin E-Depleted Human Adrenal Microsomes by Lipid Peroxidation*

Abstract

The effects of lipid peroxidation and vitamin E on the steroidogenic activities of human adrenal microsomes were studied. The vitamin E content in the microsomes could be varied by treating the lyophilized microsomes with n-pentane, without affecting the steroidogenic enzyme activities. When the level of microsomal vitamin E in the adrenal was reduced to that in other tissues such as liver and kidney, NADPH-supported lipid peroxidation increase about 200-fold, and concomitantly, the steroidogenic enzyme activities decreased. After 5 min of the lipid peroxidation reaction, 17.alpha.-hydroxylase and C17,20-lyase activities were inactivated to 13% and 18%, respectively, of the original activities, 3.beta.-Hydroxysteroid dehydrogenase-isomerase and 21-hydroxylase, however, retained 89% and 84%, respectively, of the original activities. When vitamin E was reincorporated into the extracted microsomes, neither the lipid peroxidation reaction nor the inactivation of the enzyme activities was observed. These results indicate that the high concentration of vitamin E in adrenal protects the enzymes from oxidative damage, and that the microsomal C19 steroidogenic cytochrome P-450 activities are highly sensitive to lipid peroxidation. This suggests an association between adrenal lipid peroxidation and a decrease in C19 steroid synthesis with advancing age.