PMID: 7513337Feb 1, 1994Paper

Stimulation of HMG-CoA reductase as a consequence of phenobarbital-induced primary stimulation of cholesterol 7 alpha-hydroxylase in rat liver.

Journal of Lipid Research
E Sudjana-SugiamanI Björkhem

Abstract

Among nine strains of rat, two were found that responded to phenobarbital treatment with increased activity of hepatic cholesterol 7 alpha-hydroxylase. This effect was maximal after 2-3 days of treatment and was then reduced. Interestingly the increased cholesterol 7 alpha-hydroxylase activity was associated with increased activity of hepatic HMG-CoA reductase in the two responding strains but not in the non-responding strains. In tissues other than the liver, HMG-CoA reductase activity was unaffected in responding rats. Most of the above stimulation occurred at a pretranslatory level and the mRNA levels corresponding to the two enzymes paralleled the activities. The phenobarbital treatment resulted in decreased content of free cholesterol in liver microsomes in a strain of rat that responded with increased cholesterol 7 alpha-hydroxylase activity. It was shown that depletion of cholesterol in the responding strain of rats by lymph fistulation also was associated with a parallel increase in levels of HMG-CoA reductase activity and mRNA. The findings are discussed in relation to the link between HMG-CoA reductase and cholesterol 7 alpha-hydroxylase. A primary upregulation of the cholesterol 7 alpha-hydroxylase by the cytochrome ...Continue Reading

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