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 c atalyzes the formation of estradiol fatty acid esters. These esters are lip ophilic and have prolonged hormonal activity because they are slowly metabo lized and because they slowly release estradiol. In the present study, we h ave shown that treatment of rats with clofibrate or gemfibrozil (peroxisome proliferators that are commonly used hypolipidemic drugs) markedly stimula te 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 w eeks stimulated fatty acyl-CoA: estradiol acyltransferase activity per mill igram of microsomal protein by 4-, 8-, 14- and 16-fold, respectively, when estradiol was incubated with liver microsomes and a fatty acyl-CoA. Additio nal studies showed that incubation of H-3-labeled estradiol with liver micr osomes, ATP, and coenzyme A resulted in the formation of multiple fatty aci d esters of estradiol from endogenous fatty acids in liver microsomes, and the formation of these esters was stimulated manyfold by pretreatment of ra ts with clofibrate. This study provides the first demonstration of a stimul atory effect of an environmental agent on the esterification of an estrogen .