Constitutive Androstane Receptor-vitamin D Receptor Crosstalk: Consequence on Cyp24 Gene Expression.
From: Inserm, Université Montpellier1, UMR-632, Montpellier F-34293, France.
Biochemical and biophysical research communications
- Publish Date: Aug 2007
- ISSN: 0006-291X
- Volume: 360
- Issue: 1
- Pages: 76-82
- Medium: Print
- Language: English
- Citation (JAMA): Moreau Amélie, Maurel Patrick, Vilarem Marie-José, et al. Constitutive Androstane Receptor-vitamin D Receptor Crosstalk: Consequence on Cyp24 Gene Expression.. Biochem. Biophys. Res. Commun. Aug 2007;360:76-82
Abstract
We previously reported that the pregnane X receptor (PXR) interferes with vitamin D receptor (VDR) target genes, notably CYP24, by targeting the same responsive elements. Since PXR and constitutive androstane receptor (CAR) share responsive elements in the promoter of their target genes, we wondered whether CAR also interferes with CYP24 expression. The current study shows that: (i) CAR-RXR heterodimer binds to and transactivates the proximal promoter of CYP24 (-1200/+22) and both VDRE-1 and VDRE-2 which control its expression in response to 1,25-dihydroxyvitamin D(3), (ii) androstanol an inverse agonist of hCAR inhibits transactivation of VDREs by hCAR, (iii) mutations of either VDRE-1 or -2 half sites inhibit hCAR-mediated transactivation, and (iv) in primary human hepatocytes (n =11) CITCO, a specific hCAR agonist, is an inducer of CYP24 as well as of CYP2B6 and CYP3A4 mRNAs. In conclusion, CAR/PXR and VDR bind to and transactivate the same response elements in CYP24 promoter.
Mesh Headings (Keywords): Cells, Cultured, Gene Expression, Hepatocytes, Humans, Receptors, Calcitriol, Receptors, Cytoplasmic and Nuclear, Signal Transduction, Steroid Hydroxylases, Transcription Factors
Check for Full Text / PubMed Unique Identifier (PMID): 17585873
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