This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mitchell, A. D. Articles by Goldfarb, S. Search for Related Content PubMed PubMed Citation Articles by Mitchell, A. D. Articles by Goldfarb, S.

Partial "Feedback Control" of ß-Hydroxy-ß-methylglutaryl Coenzyme A Reductase Activity in Primary Hepatocellular Carcinomas¹

Department of Pathology, The Medical School, University of Wisconsin, Madison, Wisconsin 53706

The activity of ß-hydroxy-ß-methylglutaryl coenzyme A reductase, the rate-controlling enzyme of cholesterol synthesis, was studied in normal livers and in 64 primary hepatocellular carcinomas from rats fed a basal diet or a diet containing either 2% cholestyramine or 5% cholesterol. The average enzyme activity in hepatocellular carcinomas from rats fed the basal diet was more than twice that in normal liver. Dietary cholesterol caused a reduction in activity to one-ninth of the normal hepatic enzyme activity, whereas cholestyramine feeding resulted in a 7-fold increase above the basal level. The data tended to confirm the previously documented observation that "diet-induced feedback inhibition" of cholesterol synthesis is not expressed in hepatomas, since the enzyme activity was reduced only slightly in cancers from rats fed cholesterol. However, the activities from cancers of cholestyramine-fed rats were 2.7 times greater than those from cholesterol-fed rats. Thus, a degree of control was clearly demonstrable, although it represented only 4% of that seen in normal liver. To our knowledge this is the first report of at least partial "feedback control" of ß-hydroxy-ß-methylglutaryl coenzyme A reductase activity in hepatocellular carcinomas grown in vivo.

¹ This work was supported by National Cancer Institute Grant CA15664.

² Recipient of Damon Runyon Postdoctoral Fellowship DRG-60-F.

³ Recipient of National Cancer Institute Postdoctoral Fellowship 1-F32-CA05785.

⁴ To whom requests for reprints should be addressed.

Received 10/11/77. Accepted 9/12/78.

This article has been cited by other articles:

				M. Axelson and O. Larsson 27-Hydroxylated Low Density Lipoprotein (LDL) Cholesterol Can Be Converted to 7alpha ,27-Dihydroxy-4-cholesten-3-one (Cytosterone) before Suppressing Cholesterol Production in Normal Human Fibroblasts. EVIDENCE THAT AN ALTERED METABOLISM OF LDL CHOLESTEROL CAN UNDERLIE A DEFECTIVE FEEDBACK CONTROL IN MALIGNANT CELLS J. Biol. Chem., May 31, 1996; 271(22): 12724 - 12736. [Abstract] [Full Text] [PDF]