Thyroid hormone rapidly increases cholesterol 7 alpha-hydroxylase mRNA levels in hypophysectomized rats.
The induction of hepatic cholesterol 7 alpha-hydroxylase mRNA by triiodothyronine was investigated in hypophysectomized rats. These rats exhibited markedly decreased levels of cholesterol 7 alpha-hydroxylase mRNA compared to normal controls. An increase in this mRNA could be detected within 30 min after giving triiodothyronine. A triiodothyronine dose of 0.25 microgram per 100 g of body weight, which produces 50% occupancy of hepatic nuclear thyroid hormone receptors, caused significant increases in hydroxylase mRNA levels. The half-life of cholesterol 7 alpha-hydroxylase mRNA was about 30 min and was not affected by thyroid hormone. Administration of the protein synthesis inhibitor, cycloheximide, after triiodothyronine caused superinduction. Hepatic HMG-CoA reductase mRNA levels, which are also low in livers from hypophysectomized rats, were unaffected by these doses of hormone within the 2 h time-frame examined in these studies. The results suggest that thyroid hormone may exert a primary affect on the expression of the hepatic cholesterol 7 alpha-hydroxylase gene. This could explain, in part, the hypocholesterolemic effect of thyroid hormone.
Ness
G C
GC
Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa 33612.
Pendelton
L C
LC
Zhao
Z
Z
D000818:Animals; D002790:Cholesterol 7-alpha-Hydroxylase / Q000096:biosynthesis / Q000235:genetics*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D007016:Hypophysectomy; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000494:pharmacology*
D012333:RNA, Messenger; D013963:Thyroid Hormones; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase