CHOLESTEROL-SYNTHESIS IN ISOLATED RAT HEPATOCYTES - INVITRO EFFECT OF STEROLS AND BILE-ACIDS

The in vitro effects of various sterols and bile acids on the overall rate of cholesterol synthesis in isolated adult rat hepatocytes were investigated. When rat hepatocytes were incubated with sodium-taurocholate or sodium cholate (up to 50 .mu.mol/l), no inhibition of cholesterogenesis was found. Sodium glycochenodeoxycholate reduced cholesterogenesis to a significant extent, but only at concentrations (10-50 .mu.mol/l) which were higher than those usually found in both the liver and the portal blood of the rat. When hepatocytes were incubated in the presence of protonated free bile acids (10-30 .mu.mol/l), cholesterogenesis was greatly reduced. Mono- and dihydroxy bile acids were more powerful inhibitors than the trihydroxy ones. The exposure of hepatocytes to free cholesterol (up to 200 .mu.mol/l) produced only a slight reduction of cholesterogenesis (20%); the addition of oxygenated sterols to the medium (7-ketocholesterol, 7-.alpha.-hydroxycholesterol and 25-hydrocholesterol) inhibited cholesterogenesis at concentrations lower than 40 .mu.mol/l. Cholesterol derivatives (both oxygenated sterols and free protonated bile acids) rather than cholesterol itself may be the modulators of hepatic cholesterogenesis.