Abstract
This study reports that dexamethasone (DEX) significantly induces CYP3A11, CYP3A13 and CYP3A25 mRNA expression in male and female 4 days, 3 weeks and 18 weeks old C57BL/6J mice. Furthermore, CYP3A activity, as measured by erythromycin-N-demethylation, is also significantly increased. PXR, RXRalpha and CAR are known to be involved in the induction of CYP3As. Here we report nuclear receptors PXR and RXRalpha but not CAR demonstrate gender- and age-dependent expression. Also, treatment of C57BL/6J mice with DEX induces PXR but not RXRalpha or CAR. In summary, we demonstrate DEX is not only able to up-regulate CYP3A expression and activity, but also the nuclear receptor PXR through which it may exert this effect. Furthermore, the gender- and age-dependent pattern of basal PXR and RXRalpha expression is similar to the 3 CYP3As analysed.
MeSH terms
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Age Factors
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Animals
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Constitutive Androstane Receptor
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Cytochrome P-450 CYP3A / biosynthesis*
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Dexamethasone / pharmacology
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Enzyme Induction
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Female
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Glucocorticoids / pharmacology
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Liver / drug effects
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Liver / metabolism*
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Liver Extracts / metabolism
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Male
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Membrane Proteins / biosynthesis*
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Mice
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Mice, Inbred C57BL
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Pregnane X Receptor
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RNA, Messenger / biosynthesis
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Receptors, Cytoplasmic and Nuclear / biosynthesis
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Receptors, Steroid / biosynthesis
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Retinoid X Receptor alpha / biosynthesis
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Sex Factors
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Transcription Factors / biosynthesis
Substances
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Constitutive Androstane Receptor
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Glucocorticoids
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Liver Extracts
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Membrane Proteins
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Pregnane X Receptor
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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Retinoid X Receptor alpha
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Transcription Factors
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Dexamethasone
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Cyp3a11 protein, mouse
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Cyp3a13 protein, mouse
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Cyp3a25 protein, mouse
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Cytochrome P-450 CYP3A