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  • Title: Suppression of the expression of the CYP2B1/2 gene by retinoic acids.
    Author: Yamada H, Yamaguchi T, Oguri K.
    Journal: Biochem Biophys Res Commun; 2000 Oct 14; 277(1):66-71. PubMed ID: 11027641.
    Abstract:
    The effects of 5alpha-androsten-3alpha-ol (ASE), and retinoic acids (RAs) and their precursors on the phenobarbital (PB)-mediated induction of CYP2B1 and 2B2 were examined in cultured rat hepatocytes. Two isomers of RA, 9-cis- and all-trans-RA, suppressed markedly the effect of PB on CYP2B1/2 expression, while ASE had no suppressive effect. The effect of 9-cis-RA appeared at a lower concentration than the all-trans-isomer, indicating the dominant action of the former isomer. Suppression with 9-cis-retinal was also observed, but all-trans-retinol and -retinal were without effect. These results suggest that: (1) ASE, an inverse agonist for the constitutive androstane receptor (CAR), does not play a major role in the suppression of the CYP2B; (2) 9-cis-RA suppresses CYP2B induction by reducing ligand-free retinoid X-receptors (RXR) available for dimerization with the CAR; and (3) enzymes responsible for RA formation play an important role in the mechanism governing CYP2B regulation.
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