EPINEPHRINE AND CHOLESTEROL METABOLISM IN THE DOG. HEPATIC METABOLISM OF PYRUVATE AND MEVALONATE IN VITRO

¹ Department of Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana

The administration of epinephrine in oil, 1 mg free base/kg/day for 7 days to adult male dogs, resulted in significant increases in plasma and liver cholesterol concentrations. The in vitro incorporation of C¹⁴ from pyruvate-3-C¹⁴ into cholesterol, total lipid and CO₂ and from mevalonate-2-C¹⁴ into cholesterol and CO₂ by liver slices from epinephrine-treated dogs was not different from the metabolism of these substrates by liver slices from control dogs. Liver slices from dogs fed cholesterol for 9 to 11 days showed significant decreases in the incorporation of C¹⁴ from pyruvate-3-C¹⁴ into cholesterol. Significant increases in plasma cholesterol concentrations were observed in cholesterol-fed dogs treated with epinephrine in oil, but C¹⁴ incorporation from pyruvate-3-C¹⁴ into cholesterol was almost completely inhibited in liver slices from these dogs. Decreases in C14 incorporation from pyruvate-3-C¹⁴ into cholesterol were demonstrated in liver slices taken from cholesterol-fed dogs treated with epinephrine for 2 days. Increased plasma cholesterol concentrations in epinephrinetreated dogs, therefore, did not result from increased hepatic cholesterol synthesis. Epinephrine-induced hypercholesterolemia probably resulted from an influx of extrahepatic sterol into the liver plasma cholesterol pool.