Feedback regulation of hepatic 7α-hydroxylase expression by bile salts in the hamster

David K. Spady, Jennifer A. Cuthbert, Maureen N. Willard, Robert S. Meidell

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Hepatic 7α-hydroxylase activity appears to be regulated at the transcriptional level by the quantity of bile salts fluxing through the enterohepatic circulation. Whether bile salts directly suppress 7α- hydroxylase expression at the level of the hepatocyte or do so indirectly by promoting the release or absorption of an intestinal factor has not been resolved. We have investigated the ability of primary bile salts to suppress hepatic 7α-hydroxylase expression in bile-diverted hamsters. Biliary diversion was accompanied by derepression of both hepatic 7α-hydroxylase activity (4-5-fold) and bile salt secretion (~3-fold). Derepression of hepatic 7α-hydroxylase expression could be prevented by several interventions that increase the availability of bile salts within the hepatocyte including 1) overexpression of an exogenous 7α-hydroxylase gene by adenovirus-mediated gene transfer, 2) obstruction of the common bile duct, and 3) intravenous infusions of taurocholate. In contrast, none of these interventions prevented derepression of hepatic cholesterol synthesis or significantly down-regulated hepatic low density lipoprotein receptor expression over the relatively short time course (24 h) of these studies. Together, these data indicate that primary bile salts contribute to the regulation of bile salt synthesis through feedback repression of 7α- hydroxylase expression at the level of the hepatocyte.

Original languageEnglish (US)
Pages (from-to)18623-18631
Number of pages9
JournalJournal of Biological Chemistry
Volume271
Issue number31
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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