Lipoprotein mediated regulation of 3 hydroxy 3 methylglutaryl coenzyme A reductase activity and cholesteryl ester metabolism in the adrenal gland of the rat

S. Balasubramaniam, J. L. Goldstein, J. R. Faust, G. Y. Brunschede, M. S. Brown

Research output: Contribution to journalArticle

139 Scopus citations

Abstract

In the adrenal gland of the rat, the activity of 3 hydroxy 3 methylglutaryl coenzyme A reductase, the rate controlling enzyme of cholesterol synthesis, is shown to be regulated by cholesterol carried in plasma lipoproteins. When plasma cholesterol levels were lowered 90% by administration of the drug 4 aminopyrazolopyrimidine, the cholesteryl ester content of the adrenal gland declined by more than 90%, and this was associated with a 150 to 200 fold increase in the activity of adrenal 3 hydroxy 3 methylglutaryl coenzyme A reductase and a 30 fold increase in cholesterol synthesis from [ 14C]acetate. The subsequent intravenous infusion of cholesterol contained in either rat or human high density or low density lipoproteins restored the adrenal content of cholesteryl esters and reduced the activity of 3 hydroxy 3 methylglutaryl coenzyme A reductase to basal levels. The depletion of adrenal cholesteryl esters and the enhancement in the activity of 3 hydroxy 3 methylglutaryl coenzyme A reductase that occurred in the 4 aminopyrazolopyrimidine treated rat required the action of adrenocorticotropic hormone (ACTH) since neither was observed when ACTH secretion was blocked by administration of dexamethasone. The current data indicate that the low rate of cholesterol synthesis normally observed in the rat adrenal gland is due to a suppression of the activity of 3 hydroxy 3 methylglutaryl coenzyme A reductase that is mediated by plasma lipoproteins.

Original languageEnglish (US)
Pages (from-to)1771-1779
Number of pages9
JournalJournal of Biological Chemistry
Volume252
Issue number5
StatePublished - Nov 6 1977

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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