The in vitro and in vivo effect of estradiol upon the 17 alpha-hydroxylase and C17,20-lyase activity in the ovaries of immature hypophysectomized rats.

The effect of a single injection of estradiol benzoate upon the activity of 17 alpha-hydroxylase and C17,20-lyase in the ovaries of hypophysectomized immature rats was investigated. Tritiated H2O from 17 alpha-[3H]progesterone and 14CH3COOH from 21-[14C]progesterone were the products measured to evaluate the hydroxylase and lyase activities respectively. Estradiol (E2) had no direct effect upon the activity of the enzymes in vitro even when present at twice the concentration of the substrate. However, when given in vivo, E2 reduced the activity of both enzymes. The ratio of the activities remained constant supporting the contention that both enzyme activities reside in one cytochrome P-450. Cycloheximide attenuated, but did not prevent, the reduction obtained with estrogen. Enzyme activities were reduced by E2 to a slightly lesser degree when the ovaries had been exposed in vivo to exogenous gonadotropin for 72 h. The results indicate that 17 alpha-hydroxylase and C17,20-lyase activities decrease when large doses of E2 are administered in vivo, that this effect is not directly on the enzymes, and that at least a part of this effect involves macromolecular synthesis.