Feeding status-related effects of 17 beta-estradiol on liver 3-hydroxy-3-methylglutaryl CoA reductase.
Total and expressed 3-hydroxy-3-methylglutaryl CoA reductase was determined in hepatic microsomes prepared from fasted and fed control rats and 17 beta-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 micrograms 17 beta-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% cholestyramine-diet for five days, thus presenting higher basal HMG-CoA reductase levels, the stimulatory effect of 17 beta-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 17 beta-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.
Alonso
M A
MA
Department of Physiology, University of the Basque Country Medical School, Bilbao, Spain.
Fernandez de Quincoces
A
A
Lacort
M
M
Gandarias
J M
JM
Ochoa
B
B
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004032:Diet; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008862:Microsomes, Liver / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D004958:Estradiol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases