Studies on Triiodothyronine-Induced Synthesis of Liver Mitochondrialα -Glycerophosphate Dehydrogenase in the Thyroidectomized Rat

Administration of a single small dose of triiodothymonine (T 3 ) greatly increased liver mitochondrial L-α-glycerophosphate dehydrogenase activity of thyroidectomized rats. The induction of liver mitochondrial L-α-glycerophoshate dehydrogenase by T 3 could be blocked by simultaneous administration of puromycin; in addition, time incorporation of L-leucine- 14 C into total liver proteins and into proteins of all subcellular fractions was greatly inhibited. Furthermore, puromycin blocked further induction when it was administered after the administration of T 3 . L-Ethionine prevented the induction of enzyme formation, and the inhibition could be partially reversed by L-methionine. "Pulse labeling" was used to study the incorporation of L-leucine- 14 C into liver proteins, and the data indicate that an increased rate of protein synthesis precedes the maximal increase in liver mitochondrial L-α-glycerophosphate dehydrogenase produced by T 3 -administration. These observations suggest that T 3 -induction of L-α-glycerophosphate dehydrogenase in the thyroidectomized rat results from acceleration of enzyme synthesis. Similar observations were reported earlier with the euthyroid rat. Administration of actinomycin D along with the T 3 abolished the increase of L-α-glycerophosphate dehydrogenase in liver mitochondria. The induction was also partially inhibited by 5-fluorouracil. These results indicate that the induction process depends on the formation of an adequate amount of renewable messenger-RNA molecules.