RXR is able to regulate the expression of many xenochemical metabolizing enzymes of the cytochrome P450 family acting as a dimerization agent for PPAR, LXR, PXR [100–103], but its ability to regulate the cytochrome P450 CYP2E1, involved in ethanol oxidation to acetaldehyde, needs further investigation. The promoter region of cytochrome P4504A contains an imperfect direct repeat sequence recognized by PPARα/RXR heterodimers and P4504A is induced by peroxisome proliferators [104] whereas CYP2B is induced by androstane receptor/RXR heterodimers [105]. It has been demonstrated that ethanol-fed animals show a reduced RXR expression whereas CYP2E1 mRNA increases [42, 97]. In an RXR null background, male mice but not female have a reduced expression of CYP4A, 3A, CYP2A and CYP2B mRNA [10, 106] but not of CYP2E1 [106] compared to male wild-type mice. Furthermore, when RXR null mice were challenged with ethanol, induction of CYPs expression was lower in mutant mice compared to wild-type mice [10]. In RXR KO mice CYP2E1 activity is reduced [12] and the enzyme is not induced by ethanol [107]. The apparent discrepancy between wild-type and RXR KO mice in
