Feeding Status-Related Effects of 17ß-Estradiol on Liver 3-hydroxy-3-methylglutaryl CoA Reductase

Summary

Total and expressed 3-hydroxy-3-methylglutaryl CoA reductase was determined in hepatic microsomes prepared from fasted and fed control rats and 17β-estradiol-treated rats. Plasma, liver and microsome cholesterol levels were also measured. Fasting resulted in significantly lower total and expressed specific activity of HMG-CoA reductase such that the expressed/total activity ratio doubled regardless of the endocrine status of the animals. Rats treated for either 3 or 21 days with 50 µg 17β-estradiol and starved for 24 hours exhibited greater reductase activity than untreated animals, the percentage of enzyme in effective form being maintained. When rats were fed on a commercial diet or a 4% cholesteramine-diet for five days, thus presenting higher basal HMG-CoA reductase levels, the stimulatory effect of 17β-estradiol was not statistically significant. In contrast, when total reductase was reduced by dietary cholesterol, the estrogen effect was accentuated. Long-term estradiol treatment was associated with increases in liver weight, decreases in free and total plasma cholesterol, and microsome cholesteryl ester accumulation; while short-term estradiol treatment increased plasma esterified and total cholesterol as well as the microsomal content of cholesteryl esters. These findings suggest (i) that the two 17β-estradiol treatments employed in this study are associated with higher HMG-CoA reductase levels and this is particularly apparent when cholesterol synthesis occurs at a low rate and (ii) that plasma cholesterol levels are not strictly correlated with hepatic HMG-CoA reductase activity.

Key words

HMG-CoA Reductase - Estradiol - Nutritional status - Rat liver