Presence of cholesterol 7 alpha-hydroxylase enzyme protein in COS-cells leads to increased HMG CoA reductase activity.

Transfection of COS-cells with a cDNA coding for human cholesterol 7 alpha-hydroxylase resulted in significant production of cholesterol 7 alpha-hydroxylase enzyme and intracellular accumulation of the product, 7 alpha-hydroxycholesterol. Presence of this enzyme activity was always associated with increased HMG CoA reductase activity. In five different independent transfection experiments resulting in a cholesterol 7 alpha-hydroxylase activity of 0.26 +/- 0.05 pmol/min/mg in the transfected cells, the HMG CoA reductase activity increased to 158 +/- 14% of that of the control cells (p < 0.01). This change was not associated with significant changes in the cholesterol content or LDL-receptor expression of the COS-cells. It is evident that the two key enzymes in cholesterol synthesis and degradation interact with each other also in extra-hepatic cells that are unable to degrade cholesterol into bile acids. Possible mechanisms for the finding is discussed.