COORDINATE REGULATION OF BILE-ACID BIOSYNTHETIC AND RECOVERY PATHWAYS

Intestinal and hepatic recovery of bile acids is principally mediated by sodium dependent bile acid transporters. Of these, the ileal sodium bile acid transporter (isbt) and the hepatic sodium bile acid cotrans porting polypeptide (ntcp) may be most important in determining the ef ficiency of bile mid recovery within the enterohepatic circulation. We used molecular probes to explore the relationship between the bile ac id recovery pathway, at the level of isbt and ntcp, and the biosynthet ic pathway, at the level of cholesterol 7 alpha-hydroxylase (cyp7). Ta urocholate feeding of mice suppressed ntcp, isbt and cyp7 mRNA levels as compared to controls. Cholestyramine feeding induced both cyp7 and isbt mRNA gene expression. Cholesterol feeding induced cyp7 mRNA level s but suppressed isbt gene expression. These results suggest that in m ice the bile acid recovery and biosynthetic pathways are coordinately regulated and these pathways may be responsive to the size of the bile . (C) 1996 Academic Press, Inc.