Effect of clofibrate administration on the esterification and deesterification of steroid hormones by liver and extrahepatic tissues in rats |
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Authors: | Xu Shiyao Zhu Bao Ting Conney Allan H |
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Affiliation: | Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA. |
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Abstract: | Treatment of rats with clofibrate markedly stimulated the liver microsomal esterification of estradiol, testosterone, pregnenolone, dehydroepiandrosterone, and corticosterone by acyl-CoA:steroid acyltransferase. This enzyme catalyzes the esterification of estradiol with long-chain fatty acids in both liver and extrahepatic tissues. In untreated control rats, brain had the highest acyltransferase activity per milligram of microsomal protein for estradiol esterification (3- to 4-fold higher than in the liver). Although, treatment of rats with clofibrate stimulated the esterification of estradiol by 9- to 14-fold in the liver, estradiol esterification in kidney, lung, brain, uterus, fat, and mammary glands was not increased, indicating that liver may be uniquely sensitive to induction of acyl-CoA:estradiol acyltransferase by clofibrate. In additional studies, esterase activity for hydrolysis of the oleoyl ester of estradiol was determined in control and clofibrate-treated rats. Clofibrate administration increased esterase activity by an average of 107% in fat and 70% in liver. The results indicate that treatment of rats with clofibrate stimulates the hepatic formation of highly lipophilic fatty acid esters that can be hydrolyzed in the liver and in extrahepatic tissues to the parent steroid hormone by a clofibrate-inducible esterase. |
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Keywords: | Synthesis and metabolism of steroid esters Fatty acid esters of steroid hormones Deesterification of steroid fatty acid esters Acyl-CoA:estradiol acyltransferase Induction of estradiol esterification Induction of testosterone esterification |
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