Abstract
To investigate the hypothesis that estrogen-induced increases in progesterone production are due to estrogen stimulation of cholesterol synthesis, rabbit corpora lutea were incubated for 3 and 8 h with estradiol-17# in the absence or presence of AY-9944 (an inhibitor of cholesterol synthesis). Addition of estradiol to the medium either with or without the inhibitor significantly increased (P<0.05) progesterone mass at both incubation intervals. However, utilization of ‘4C-acetate for progesterone synthesis was blocked by AY-9944. There were no significant treatment effects on 20n OH-progesterone mass at 3 or 8 h. AY-9944 decreased (P<0.05) ‘4C-acetate incorporation into 2Ocs-OH at 3 h, but was ineffective at 8 h. Cholesterol concentration was reduced (P<0.05) below controls by AY-9944 + estradiol at 8 h. No other treatment effects on mass were observed. AY-9944 blocked de novo synthesis of cholesterol as denoted by a decrease in ‘� C-acetate incorporation into the sterol. Estradiol failed to overcome the inhibition. These results indicate that AY-9944 is a potent inhibitor of cholesterol synthesis in rabbit corpora lutea and that estradiol stimulation of progesterone synthesis is not dependent upon de novo cholesterol synthesis from acetate.
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