Molecular Pharmacology, Vol 3, 44-51, Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics

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

¹ Department of Biochemistry and the Nutrition and Metabolism Research Laboratory, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112

Administration of a single small dose of triiodothymonine (T₃) greatly increased liver mitochondrial L--glycerophosphate dehydrogenase activity of thyroidectomized rats.

The induction of liver mitochondrial L--glycerophoshate dehydrogenase by T₃ could be blocked by simultaneous administration of puromycin; in addition, time incorporation of L-leucine-¹⁴C 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 T₃. 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-¹⁴C into liver proteins, and the data indicate that an increased rate of protein synthesis precedes the maximal increase in liver mitochondrial L--glycerophosphate dehydrogenase produced by T₃-administration. These observations suggest that T₃-induction of L--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 T₃ abolished the increase of L--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.

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ACKNOWLEDGMENTS This work was supported by a grant from the United States Public Health Service, TIGM-648-05. Time experimental data are taken from a dissertation submitted by Kai-Lin Lee to the Graduate School of Tulane University in partial fulfillment of the requirements for the degree of Doctor of Philosophy, 1966.