EFFECT OF 5H-ALPHA-CHOLEST-8(14)-EN-3-BETA-OL-15-ONE ON CHOLESTEROL-METABOLISM IN CULTURED RABBIT HEPATOCYTES

The effects of 15-ketosterol on the following parameters of cholestero l metabolism were studied: a) cholesterol synthesis, b) apolipoprotein secretion; c) bile acid synthesis. 15-Ketosterol used at its therapeu tic concentration (0.25 muM) inhibits cholesterol synthesis by 50%. De creases in total apo B and apo E secretion by 70-80 and 40-50%, respec tively, were observed at this concentration of the drug. Synthesis and secretion of the total C-14-labeled protein fraction remained unchang ed. Addition of 15-ketosterol to incubation medium containing HDL2 did not decrease bile acid synthesis in hepatocytes. The results indicate that 15-ketosterol may manifest its hypocholesterolemic effect by inh ibiting cholesterol synthesis in liver and simultaneously decreasing s ecretion of apo B-containing lipoprotein particles.