Stimulative and inhibitive effects of estrogen on cholesterol synthesis in rats.

Abstract

Effect of estradiol on hepatic cholesterol synthesis, acetate and mevalonate incorporation into 3β-hydroxysterols in vitro and acetate incorporation in vivo, was examined in relation to the effect of this steroid on plasma and liver cholesterol levels in male rats. A 3-day treatment with estradiol, daily 0.3 mg/rat, caused a decrease in plasma cholesterol level with a concomitant increase in liver cholesterol level and reduced the rate of hepatic cholesterol synthesis from both acetate and mevalonate. Statistical analysis revealed a) significant positive correlations between plasma cholesterol level and the rate of cholesterol synthesis in the liver, and between acetate incorporation and mevalonate incorporation, and b) significant negative correlations between plasma cholesterol level and liver cholesterol level, and between liver cholesterol level and the rate of cholesterol synthesis in the liver. By contrast, a 3-week treatment with estradiol (0.3 mg/rat, twice a week) produced a marked hypercholesterolemia and a significant stimulation of cholesterol synthesis from acetate both in vitro and in vivo, but not from mevalonate. Liver cholesterol levels after chronic treatment were in normal range. These data suggest that the inhibition of hepatic cholesterol synthesis after the acute treatment with estradiol is indirectly caused by the cholesterol accumulated in the liver as the result of cholesterol shifting action of this hormone and the stimulation after the chronic treatment is the effect of estradiol upon cholesterol synthesis to induce hypercholesterolemia.