Regulation of hepatic sterol metabolism in the rat. Parallel regulation of activity and mRNA for 7α-hydroxylase but not 3-hydroxy-3-methylglutaryl- coenzyme a reductase or low density lipoprotein receptor

David K. Spady, Jennifer A. Cuthbert

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

In vivo regulation of hepatic sterol metabolism was examined in the rat. Sodium cholate markedly suppressed hepatic 7α-hydroxylase mRNA levels and activity when fed to rats on a low cholesterol diet. Sterol balance was maintained solely by decreasing hepatic cholesterol synthesis. Compensatory mechanisms were inadequate when cholate was fed to rats on a high cholesterol diet and massive amounts of cholesterol accumulated in the liver and plasma. Suppression of bile salt synthesis was not responsible since cholate did not suppress 7α-hydroxylase activity when fed to rats on a high cholesterol diet. Moreover, total hepatic low density lipoprotein receptor activity was not suppressed even though liver cholesteryl ester levels were increased more than 350-fold. Changes in 7α-hydroxylase activity were always accompanied by parallel changes in mRNA, whereas mRNA levels for 3-hydroxy-3-methylglutaryl- coenzyme A (HMG-CoA) reductase were reduced by 50% or less, even when cholesterol synthesis was suppressed by 98%. HMG-CoA reductase and low density lipoprotein receptor activities were regulated independently although mRNA levels for these two proteins were coordinately regulated. These findings indicate that 7α-hydroxylase is controlled by mRNA levels, whereas in vivo cholesterol synthesis is predominantly controlled by posttranscriptional regulation of HMG-CoA reductase activity.

Original languageEnglish (US)
Pages (from-to)5584-5591
Number of pages8
JournalJournal of Biological Chemistry
Volume267
Issue number8
StatePublished - 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Regulation of hepatic sterol metabolism in the rat. Parallel regulation of activity and mRNA for 7α-hydroxylase but not 3-hydroxy-3-methylglutaryl- coenzyme a reductase or low density lipoprotein receptor'. Together they form a unique fingerprint.

  • Cite this