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.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
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
C2 - 1544932
AN - SCOPUS:0026775156
SN - 0021-9258
VL - 267
SP - 5584
EP - 5591
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 8
ER -