Failure of intravenous infusion of taurocholate to down-regulate cholesterol 7α-hydroxylase in rats with biliary fistulas

Background/Aims: The decrease in cholesterol 7α-hydroxylase induced by intraduodenal infusion of taurocholate in bile fistula rats may be indirect, i.e., mediated through release or absorption of an intestinal factor in response to the presence of bile salts in the intestine. The aim of this study was to determine if negative feedback regulation of cholesterol 7α-hydroxylase can be shown when equimolar concentrations of taurocholate are administered intravenously, thus bypassing the intestine. Methods: After 96 hours of biliary diversion, taurocholate (36 μmol·h −1·100 g rat −1) was infused into the rats either intravenously or intraduodenally for the final 24 hours. Livers were then harvested for analysis of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase specific activity, cholesterol 7α-hydroxylase specific activity, messenger RNA levels, and transcriptional activity. Results: Intraduodenally administered taurocholate significantly decreased HMG-CoA reductase and cholesterol 7α-hydroxylase specific activity by more than 50% and cholesterol 7α-hydroxylase steady-state messenger RNA levels and transcriptional activity by 50%–75%. In contrast, intravenous administration of taurocholate failed to down-regulate either cholesterol 7α-hydroxylase or HMG-CoA reductase. Conclusions: Passage of taurocholate through the intestine strongly potentiates negative feedback regulation of cholesterol 7α-hydroxylase. A putative intestinal factor, released or absorbed in the presence of bile acids in the intestinal lumen, may play a role in the regulation of bile acid synthesis.