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Publication : PPARalpha-dependent induction of liver microsomal esterification of estradiol and testosterone by a prototypical peroxisome proliferator.

First Author  Xu S Year  2001
Journal  Endocrinology Volume  142
Issue  8 Pages  3554-7
PubMed ID  11459802 Mgi Jnum  J:115613
Mgi Id  MGI:3691993 Doi  10.1210/endo.142.8.8330
Citation  Xu S, et al. (2001) PPARalpha-dependent induction of liver microsomal esterification of estradiol and testosterone by a prototypical peroxisome proliferator. Endocrinology 142(8):3554-7
abstractText  Fatty acyl-coenzyme A:estradiol acyltransferase in liver microsomes catalyzes the formation of estradiol fatty acid esters. These estrogen esters are extremely lipophilic and have prolonged hormonal activity because they are slowly metabolized and slowly release estradiol. Our previous studies showed that treatment of female rats with clofibrate or gemfibrozil (peroxisome proliferators commonly used as hypolipidemic drugs) markedly stimulated the liver microsomal esterification of estradiol. Although clofibrate administration is a potent inducer of liver microsomal fatty acyl-coenzyme A:estradiol acyltransferase in rats, it is a poor inducer in mice. In contrast to these observations, Wy-14,643 (an exceptionally potent prototypical peroxisome proliferator) is a strong inducer of fatty acyl-coenzyme A:estradiol acyltransferase in mice. To explore the role of PPARalpha in the induction of fatty acyl-coenzyme A:estradiol acyltransferase and fatty acyl-coenzyme A:testosterone acyltransferase activities by peroxisome proliferators, we fed 0.1% Wy-14,643 to female wild-type and PPARalpha null mice for 11 d. The liver microsomal acyl-coenzyme A:estradiol acyltransferase and acyl-coenzyme A:testosterone acyltransferase activities were increased 4- to 5-fold in wild-type mice fed Wy-14,643, but no increase was observed in null mice. These results demonstrate that induction of acyl-coenzyme A:estradiol acyltransferase and acyl-coenzyme A:testosterone acyltransferase activities by a prototypical peroxisome proliferator is dependent on PPARalpha.
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