Effect of estrogens on beta-hydroxy-beta-methylglutaryl coenzyme A reductase activity and cholesterol levels

The effect of estrogens on hepatic beta-hydroxy-beta-methylglutaryl coenzyme A reductase activity and cholesterol in serum and liver of ovariectomized rats on normal diet 2% cholestyramine diet or 2% cholesterol diet was investigated. Estrogen administration to ovariectomized rats on normal diet resulted in increased reductase activity and was correlated with decreased serum cholesterol and increased liver cholesterol levels with mestranol (ME), ethinyl estradiol (EE) and estradiol benzoate (EB, 250 microgram) but increased serum and liver cholesterol levels with 25 microgram and 100 microgram EB administration. The increased stimulation of reductase activity by estrogen administration was abolished when rats were fed a 2% cholesterol diet. Cholestryramine feeding markedly increased reductase activity in livers of ovariectomized rats. These studies show that estrogens are not absolutely required for the stimulation of reductase activity and therefore is consistent with the model in which cholesterol functions as a feedback repressor of reductase activity.