PPARα-dependent induction of liver microsomal esterification of estradiol and testosterone by a prototypical peroxisome proliferator

Shiyao Xu, Bao Ting Zhu, Valerie Turan, Ivan Rusyn, Ronald Thurman, Jeffrey Maurice Peters, Frank J. Gonzalez, Allan H. Conney

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 PPARα 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 PPARα 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 PPARα.

Original languageEnglish (US)
Pages (from-to)3554-3557
Number of pages4
JournalEndocrinology
Volume142
Issue number8
DOIs
StatePublished - Jan 1 2001

Fingerprint

Peroxisome Proliferators
Acyltransferases
Peroxisome Proliferator-Activated Receptors
Esterification
Acyl Coenzyme A
Testosterone
Estradiol
Liver
Clofibrate
Esters
Gemfibrozil
Hypolipidemic Agents
Liver Microsomes
Fatty Liver
Estrogens
Fatty Acids

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Xu, Shiyao ; Zhu, Bao Ting ; Turan, Valerie ; Rusyn, Ivan ; Thurman, Ronald ; Peters, Jeffrey Maurice ; Gonzalez, Frank J. ; Conney, Allan H. / PPARα-dependent induction of liver microsomal esterification of estradiol and testosterone by a prototypical peroxisome proliferator. In: Endocrinology. 2001 ; Vol. 142, No. 8. pp. 3554-3557.
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abstract = "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 PPARα 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 PPARα 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 PPARα.",
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PPARα-dependent induction of liver microsomal esterification of estradiol and testosterone by a prototypical peroxisome proliferator. / Xu, Shiyao; Zhu, Bao Ting; Turan, Valerie; Rusyn, Ivan; Thurman, Ronald; Peters, Jeffrey Maurice; Gonzalez, Frank J.; Conney, Allan H.

In: Endocrinology, Vol. 142, No. 8, 01.01.2001, p. 3554-3557.

Research output: Contribution to journalArticle

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T1 - PPARα-dependent induction of liver microsomal esterification of estradiol and testosterone by a prototypical peroxisome proliferator

AU - Xu, Shiyao

AU - Zhu, Bao Ting

AU - Turan, Valerie

AU - Rusyn, Ivan

AU - Thurman, Ronald

AU - Peters, Jeffrey Maurice

AU - Gonzalez, Frank J.

AU - Conney, Allan H.

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N2 - 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 PPARα 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 PPARα 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 PPARα.

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