FIGURE 6.

atRA represses CYP2D6 expression. A, hepatic levels of atRA and 13cRA in mouse liver tissues (n = 3–4; *, p < 0.05; **, p < 0.01, one-way ANOVA versus virgin). B, Tg-CYP2D6 mice were injected with atRA (5 mg/kg/day intraperitoneally for 5 days). CYP2D6 and Shp mRNA expression was determined by qRT-PCR. C, liver S9 fractions were prepared from the liver tissues of Tg-CYP2D6 mice treated with vehicle or atRA, and CYP2D6 phenotyping was performed using debrisoquine (200 μm) (n = 4, mean ± S.D.; *, p < 0.05, Student's t test versus vehicle). Data shown are the metabolite production rate in pmol/min/mg of protein. D, recruitment of SHP, HNF4α, and RNA polymerase II to CYP2D6 promoter was analyzed by ChIP assay (n = 4, mean ± S.D.; *, p < 0.05; **, p < 0.01, Student's t test versus vehicle). E, proposed model for CYP2D6 induction during pregnancy. The red arrows indicate pregnancy-related changes in the hepatic contents or expression levels.