Regulation and induction of CYP3A11, CYP3A13 and CYP3A25 in C57BL/6J mouse liver.
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.
Down
M J
MJ
Department of Pharmacology, School of Pharmacy and Biomedical Sciences, St Michaels Building, University of Portsmouth, White Swan Road, Portsmouth, UK.
Arkle
S
S
Mills
J J
JJ
D000367:Age Factors; D000818:Animals; D000090702:Constitutive Androstane Receptor; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008110:Liver Extracts / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D011987:Receptors, Steroid / Q000096:biosynthesis; D047490:Retinoid X Receptor alpha / Q000096:biosynthesis; D012737:Sex Factors; D014157:Transcription Factors / Q000096:biosynthesis
D000090702:Constitutive Androstane Receptor; D005938:Glucocorticoids; D008110:Liver Extracts; D008565:Membrane Proteins; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D047490:Retinoid X Receptor alpha; D014157:Transcription Factors; D003907:Dexamethasone; C496508:Cyp3a11 protein, mouse; C496509:Cyp3a13 protein, mouse; C517429:Cyp3a25 protein, mouse; D051544:Cytochrome P-450 CYP3A