Estrogen-Dependent Regulation of the Expression of Hepatic Cyp2b and 3a Isoforms: Assessment Using Aromatase-Deficient Mice

doi:10.1006/taap.2002.9366

Toxicology and Applied Pharmacology

Volume 180, Issue 1, 1 April 2002, Pages 1-10

https://doi.org/10.1006/taap.2002.9366 Get rights and content

Abstract

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 6β- and 16α-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 β-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 β-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.

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Regular ArticleEstrogen-Dependent Regulation of the Expression of Hepatic Cyp2b and 3a Isoforms: Assessment Using Aromatase-Deficient Mice

Abstract

Anal. Biochem.

J. Biol. Chem.

Dev. Brain Res.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun

Biochem. Pharmacol.

Toxicol. Lett.

Adv. Pharmacol.

Brain Res.

Arch. Biochem. Biophys.

Arch. Biochem. Biophys.

Arch. Biochem. Biophys.

Arch. Biochem. Biophys.

Arch. Biochem. Biophys.

Arch. Biochem. Biophys.

Biochim. Biophys. Acta

Comparison of three actin-coding sequences in the mouse: Evolutionary relationships between the actin genes of warm-blooded vertebrates

J. Mol. Evol.

Neuroanatomical specificity in the co-localization of aromatase and estrogen receptors

J. Neurobiol.

Human placental 17β-estradiol dehydrogenase: Enzymatic activity in the last weeks of pregnancy and electrophoretic data

Horm. Res.

Fetal testosterone in mice: Effect of gestational age and cannabinoid exposure

J. Endocrinol.

Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene

Proc. Natl. Acad. Sci. USA

Changes in aromatase activity in the rat brain during embryonic, neonatal, and infantile development

Endocrinology

Enzymology of rat liver cytochrome P-450

Novel properties of human placental aromatase as cytochrome P-450: Purification and characterization of a unique form of aromatase

J. Biochem.

Regular Article
Estrogen-Dependent Regulation of the Expression of Hepatic Cyp2b and 3a Isoforms: Assessment Using Aromatase-Deficient Mice