A rapid effect of thyroxine on accumulation of diacylglycerols and on activation of protein kinase C in liver cells

L-Thyroxine rapidly stimulated the accumulation of diacylglycerols in isola ted hepatocytes and in liver when lipids were prelabeled with [C-14]oleic a cid or with [C-14]CH3COONa. Perfusion of the liver of hypothyroid animals w ith L-thyroxine-containing solution or incubation of liver fragments with t he hormone increased the content of diacylglycerols in the liver cells. The increase in [C-14]diacylglycerol level in the liver cells was accompanied by a decrease in the level of [C-14]phosphatidylcholine, whereas contents o f other C-14-labeled phospholipids, such as phosphatidylethanolamine, sphin gomyelin, lysophosphatidylcholine, phosphatidylinositol (PtdIns), phosphati dylinositol-4-phosphate (PtdIns4P), and phosphatidylinositol-4,5-bis-phosph ate (PtdIns(4,5)P-2), and of C-14-labeled fatty acids were the same as in t he control. The L-thyroxine- induced accumulation of diacylglycerols in hep atocytes was not affected by neomycin but was inhibited by propranolol. Inc ubation of hepatocytes prelabeled with [C-14]oleic acid with L-thyroxine an d ethanol (300 mM) was accompanied by generation and accumulation of [C-14] phosphatidylethanol that was partially suppressed by 1-(5-isoquinolinesulfo nyl)-2-methylpiperazine (H7). L-Thyroxine was responsible for the transloca tion of protein kinase C from the cytosol into the membrane fraction and fo r a many-fold activation of the membrane-bound enzyme. D-Thyroxine failed t o affect the generation of diacylglycerols in hepatocytes and the activity of protein kinase C.