Modulation of MDR1 and CYP3A Expression by Dexamethasone: Evidence for an Inverse Regulation in Adrenals

A strong overlap exists between gp170 and CYP3A substrates and inducers. In order to investigate a putative coregulation of MDR and CYPA gene expression, we measured their transcripts in human liver and after dexamethasone treatment in HepG2 cells or in different mouse tissues. In human liver, we ob...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1998-11, Vol.252 (2), p.392-395
Main Authors: Sérée, E., Villard, P.H., Hevér, A., Guigal, N., Puyoou, F., Charvet, B., Point-Scomma, H., Lechevalier, E., Lacarelle, B., Barra, Y.
Format: Article
Language:English
Subjects:
Adrenal Glands - drug effects
Adrenal Glands - metabolism
Animals
Aryl Hydrocarbon Hydroxylases
ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis
Base Sequence
Cell Line
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System - biosynthesis
Cytochrome P-450 Enzyme System - genetics
Dexamethasone - pharmacology
DNA Primers - genetics
Enzyme Induction - drug effects
Gene Expression - drug effects
Genes, MDR - drug effects
Humans
In Vitro Techniques
Liver - drug effects
Liver - metabolism
Mice
Oxidoreductases, N-Demethylating - biosynthesis
Oxidoreductases, N-Demethylating - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
Tissue Distribution
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Summary:A strong overlap exists between gp170 and CYP3A substrates and inducers. In order to investigate a putative coregulation of MDR and CYPA gene expression, we measured their transcripts in human liver and after dexamethasone treatment in HepG2 cells or in different mouse tissues. In human liver, we observed no correlation between MDR1 and CYP3A4 expression, whereas these genes were coinduced by dexamethasone in HepG2 cells. In mouse liver treated with dexamethasone, mdr1b and Cyp3a were induced (5- and 2-fold, respectively). In adrenals, the main expressing gp170 tissue, Cyp3a, was increased while mdr1b was repressed (−51%). The expression of mdr1b increased in heart, brain, and colon and decreased in lung and kidney but Cyp3a was not detectable. In conclusion, human hepatic CYP3A4 and MDR1 are not corregulated but are coinducible.In vivomurine mdr1b and Cyp3a are coregulated by dexamethasone in liver and inversely regulated in adrenals.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1998.9662