Injected 7-OXO Cholesterol and Plant Sterol Derivatives and Hepatic Cholesterogenesis

We have demonstrated that intravenously administered cholesterol is an effective inhibitor of hepatic cholesterogenesis, while comparable treatments with plant sterols are ineffective (1). A possible explanation for the divergence in the metabolic effects of the two sterol types exists in the observation (2,3) that rat liver enzymes are incapable of converting plant sterols to the 7a-hydroxy derivatives, which may be the active feed-back regulators of cholesterogenesis. Work with primary liver cell cultures and fibroblasts has shown that the 7-oxo derivatives of cholesterol are much more powerful inhibitors of cholesterol biosynthesis than is cholesterol itself (4). Furthermore, 7αhydroxylation is known to be the rate limiting step in bile acid formation (5), and both 7α and 7β-hydroxy cholesterols are inhibitors of bile acid biosynthesis (6).