2002年4月
Estrogen-dependent regulation of the expression of hepatic Cyp2b and 3a isoforms: Assessment using aromatase-deficient mice
TOXICOLOGY AND APPLIED PHARMACOLOGY
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- 巻
- 180
- 号
- 1
- 開始ページ
- 1
- 終了ページ
- 10
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1006/taap.2002.9366
- 出版者・発行元
- ACADEMIC PRESS INC ELSEVIER SCIENCE
The role of estrogen in the expression and induction of hepatic Cyp2b and Cyp3a isoforms was studied using mice [Ar (-/-) mice] lacking aromatase, a key enzyme for estrogen biosynthesis. The expression of P450s was determined by reverse transcription-polymerase chain reaction, immunoblotting, and measuring testosterone 6beta- and 16alpha-hydroxylase activity as markers. Basic expression of Cyp3a11 mRNA and protein was seen in both sexes of Ar (+/+) mice. Disruption of the aromatase gene caused an increase in the expression of Cyp3a11 protein, although the mRNA level remained unchanged. Female-specific Cyp3a41 disappeared in Ar (-/-) mice, and this could not be reversed by administration of exogenous beta-estradiol to adult knockout mice. The constitutive expression of female-specific Cyp2b9 also disappeared on disrupting the aromatase gene. However, in clear contrast to Cyp3a41, some individual Ar (-/-) mice exhibited expression of this form following treatment with exogenous beta-estradiol. Disruption of the aromatase gene had no effect on PB-mediated induction of Cyp2b10 or on the noninducible nature of Cyp2b9, Cyp3a11, and Cyp3a41. These results suggest that (1) Cyp3a11 is suppressed by estrogen; (2) the expression of female-specific Cyp3a41. is programmed by neonatal and/or infantile exposure to estrogen; (3) maintenance of the expression of female-specific Cyp2b9 requires estrogen in adults; and (4) endogenous estrogen plays little, if any, role in the mechanism by which PB induces Cyp2b10. (C) 2002 Elsevier Science (USA).
- リンク情報
- ID情報
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- DOI : 10.1006/taap.2002.9366
- ISSN : 0041-008X
- PubMed ID : 11922772
- Web of Science ID : WOS:000175023300001