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 Citations (Scopus)

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 - Mar 15 1992

Fingerprint

LDL Receptors
Coenzymes
Sterols
Mixed Function Oxygenases
Metabolism
Rats
Oxidoreductases
Cholesterol
Messenger RNA
Liver
Nutrition
Cholates
Diet
Sodium Cholate
Cholesterol Esters
Bile Acids and Salts
Plasmas
3-hydroxy-3-methylglutaryl-coenzyme A
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{a41f9164077442b1b5b56fad83e43807,
title = "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",
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.",
author = "Spady, {David K.} and Cuthbert, {Jennifer A.}",
year = "1992",
month = "3",
day = "15",
language = "English (US)",
volume = "267",
pages = "5584--5591",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "8",

}

TY - JOUR

T1 - Regulation of hepatic sterol metabolism in the rat

T2 - Parallel regulation of activity and mRNA for 7α-hydroxylase but not 3-hydroxy-3-methylglutaryl-coenzyme a reductase or low density lipoprotein receptor

AU - Spady, David K.

AU - Cuthbert, Jennifer A.

PY - 1992/3/15

Y1 - 1992/3/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0026775156&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026775156&partnerID=8YFLogxK

M3 - Article

VL - 267

SP - 5584

EP - 5591

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 8

ER -