Stimulatory effect of clofibrate and gemfibrozil administration on the formation of fatty acid esters of estradiol by rat liver microsomes.

Fatty acyl-coenzyme A (CoA):estradiol acyltransferase in liver microsomes catalyzes the formation of estradiol fatty acid esters. These esters are lipophilic and have prolonged hormonal activity because they are slowly metabolized and because they slowly release estradiol. In the present study, we have shown that treatment of rats with clofibrate or gemfibrozil (peroxisome proliferators that are commonly used hypolipidemic drugs) markedly stimulate the liver microsomal esterification of estradiol. Administration of 0.15, 0.30, 0.45, or 0.60% clofibrate in an AIN-76A diet to female rats for 4 weeks stimulated fatty acyl-CoA:estradiol acyltransferase activity per milligram of microsomal protein by 4-, 8-, 14- and 16-fold, respectively, when estradiol was incubated with liver microsomes and a fatty acyl-CoA. Additional studies showed that incubation of (3)H-labeled estradiol with liver microsomes, ATP, and coenzyme A resulted in the formation of multiple fatty acid esters of estradiol from endogenous fatty acids in liver microsomes, and the formation of these esters was stimulated manyfold by pretreatment of rats with clofibrate. This study provides the first demonstration of a stimulatory effect of an environmental agent on the esterification of an estrogen.