The effects of 15-ketosterol on cholesterol metabolism in cultured rabbit hepatocytes were characterized by the following parameters: a) cholesterol synthesis, b) apo B and apo E secretion, c) bile acid synthesis. 15-Ketosterol used at therapeutic concentration (0.25 microM) reduced cholesterol synthesis (by 50%). Marked inhibition (by 70%) of apo B and apo E secretion was observed for this agent. Synthesis and secretion of the total [14C]-labeled protein remaining unchanged. 15-Ketosterol did not influence the bile acid synthesis in primary culture of rabbit hepatocytes. These results are suggestive of a new putative mechanism of hyperlipidemic action of 15-ketosterol by a simultaneous decrease of hepatic cholesterol synthesis and secretion of apo B-containing particles.
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