A direct relationship between the amount of sterol lost from rat hepatocytes and the increase in activity of HMG-CoA reductase.

Incubation of rat hepatocytes in a sterol-free medium containing 1.5% albumin resulted in loss of cholesterol from the cells and increased activity of HMG-CoA reductase. Addition of egg-lecithin dispersions to the hepatocytes resulted in increased rates of sterol efflux and increased levels of reductase. The increase in enzyme activity after three hours incubation was directly proportional to the amount of cholesterol lost by the cells to the medium during the first 45 min of incubation. Sterol loss preceded the increase in enzyme activity. The data support the view that one mode of regulation of hepatic HMG-CoA reductase is dependent on the relative rates of movement of cholesterol into and out of cells.