Stimulatory effect of clofibrate and gemfibrozil administration on the formation of fatty acid esters of estradiol by rat liver microsomes. J Pharmacol Exp Ther 296

Fatty acyl-coenzyme A (CoA):estradiol acyltransferase in liver microsomes catalyzes the formation of estradiol fatty acid es-ters. 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 estra-diol. 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 microso-mal 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 3H-labele