FIG. 4.

Cyp8b1, but not Cyp7A1, is critically dependent on LRH-1. (A) Scheme depicting neutral BA biosynthetic enzymatic pathway. (B) Expression profile of key genes involved in BA biosynthesis with Cyp8b1, but not Cyp7a1, and impaired in LRH-1^hep−/− mice. Relative mRNA expression levels of the indicated genes of the BA synthesis pathway in the livers of control LRH-1^L2/L2 (n = 9) and mutant LRH-1^hep−/− (n = 9) littermates are shown. Values were normalized to cyclophilin and expressed as percent change to control LRH-1^L2/L2 mice. (C) CYP8B1 immunoblotting performed on liver extracts of LRH-1^L2/L2 and LRH-1^hep−/− mice. (D and E) LXR-mediated activation of Cyp7a1 is not dependent on the presence of LRH-1. (D) Relative mRNA expression levels of the indicated genes in the livers of either control LRH-1^L2/L2 (n = 4) mice treated with vehicle (Veh) or control LRH-1^L2/L2 (n = 5) and mutant LRH-1^hep−/− (n = 4) mice treated with the LXR agonist T0901317 (T09; 50 mg/kg/day) for 7 days. Significant differences between vehicle and T0901317-treated cohorts are indicated with lowercase a's (P < 0.05), while significant differences between T0901317-treated control and mutant cohorts are indicated with asterisks. *, P < 0.05; **, P < 0.01; ***, P < 0.001. (E) Relative mRNA expression levels of Lrh-1 and Cyp7a1 in the livers of control LRH-1^L2/L2 (n = 4) and mutant LRH-1^hep−/− (n = 10) mice fed a high-cholesterol (2%) diet for 1 week. Significant differences between groups are indicated. ***, P < 0.001.