PPARalpha-dependent induction of liver microsomal esterification of estradiol and testosterone by a prototypical peroxisome proliferator
| Autor: | Frank J. Gonzalez, Ivan Rusyn, Jeffrey M. Peters, Ronald G. Thurman, Allan H. Conney, Shiyao Xu, Valerie K. Turan, Bao Ting Zhu |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Peroxisome proliferator-activated receptor Receptors Cytoplasmic and Nuclear Mice Endocrinology Internal medicine medicine Gemfibrozil Animals Testosterone Clofibrate chemistry.chemical_classification Mice Knockout Esterification Estradiol Fatty acid Peroxisome Pyrimidines chemistry Estrogen Acyltransferase Microsomes Liver Female Peroxisome Proliferators hormones hormone substitutes and hormone antagonists Acyltransferases medicine.drug Transcription Factors |
| Zdroj: | Endocrinology. 142(8) |
| ISSN: | 0013-7227 |
| Popis: | 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 PPARa in the induction of fatty acyl-coenzyme A:estradiol acyltransferase and fatty acylcoenzyme A:testosterone acyltransferase activities by peroxisome proliferators, we fed 0.1% Wy-14,643 to female wild-type and PPARa null mice for 11 d. The liver microsomal acylcoenzyme 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 acylcoenzyme A:testosterone acyltransferase activities by a prototypical peroxisome proliferator is dependent on PPARa. (Endocrinology 142: 3554 ‐3557, 2001) |
| Databáze: | OpenAIRE |
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