Rapid increase in hepatic HMG CoA reductase activity and in vivo cholesterol synthesis after Triton WR 1339 injection.

Triton WR 1339, injected intravenously into rats, caused a 12% decrease in hepatic cholesterol within 30 minutes and a 34% decrease after 2 hours. An early and progressive increase in plasma cholesterol and triglycerides was also confirmed. Although hepatic HMG Coa reductase activity was unchanged after 30 minutes, it had increased seven-fold after 105 minutes. In vivo cholesterol synthesis measured by determining incorporation of intraperitoneally-injected 3H2O into cholesterol also showed an early increase, suggesting that the enzyme was rate controlling for cholesterogenesis under conditions of rapid stimulation. These findings strongly suggest that Triton WR 1339 stimulates hepatic cholesterogenesis by depleting hepatic cholesterol and trapping it in the blood compartment. The rapidity with which the drug acts supports the hypothesis that hepatocellular flux of cholesterol or its derivatized product could mediate the diurnal and hormonally induced fluctuations of cholesterogenesis.