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  • Title: LXR alpha is the dominant regulator of CYP7A1 transcription.
    Author: Gupta S, Pandak WM, Hylemon PB.
    Journal: Biochem Biophys Res Commun; 2002 Apr 26; 293(1):338-43. PubMed ID: 12054605.
    Abstract:
    Cholesterol 7 alpha-hydroxylase (CYP7A1) catalyzes the rate-limiting step in the classic pathway of bile acid biosynthesis. Dietary cholesterol stimulates CYP7A1 transcription via activation of oxysterol receptor, LXR alpha, whereas bile acids repress transcription through FXR-mediated induction of SHP protein. The aim of this study was to determine the quantitative role that LXR- and FXR-regulated pathways play in regulating CYP7A1 and SHP in both rat and hamster models. In rats fed a 2% cholesterol diet, both SHP and CYP7A1 mRNA levels were elevated. The inability to induce CYP7A1 mRNA levels by cholesterol feeding in hamsters led to a decline in SHP mRNA levels. Elimination of hepatic bile acid flux by cholestyramine or bile fistula resulted in a marked repression of rat SHP mRNA levels. These results suggest that under conditions of both SHP and LXR alpha activation, stimulatory effect of LXR alpha overrides the inhibitory effect of FXR and results in an induction of rat CYP7A1 mRNA levels.
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