Inhibitory Effects of Tunicamycin and 2-Deoxyglucose on Thyroglobulin Synthesis

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Abstract
The kinetic incorporation of labeled sugars and amino acids by rat thryoid hemilobes was measured in the presence of 2-deoxyglucose and tunicamycin, inhibitors of the glycosylation of glycoproteins. With either inhibitor the carbohydrate content of exocytosed thyroglobulin was only slightly decreased (< 20% of control), whereas the rate of exocytosis was strongly inhibited (by 60-80%). As no intracellular accumulation or proteolysis of non-glycosylated molecules was detected, the reduced rate of thyroglobulin release seems essentially due to a decrease in protein synthesis. In a whole cell system (hemilobes), it is impossible to uncouple glycosylation and protein synthesis by incubation with tunicamycin; 50 .mu.g/ml tunicamycin for 270 min inhibited total [3H]glucosamine and 14C-labeled amino acid incorporation by 65 and 33%, respectively. In cell-free incubation of thyroid rough microsomes, glycosylation was blocked by the same tunicamycin concentration (90% inhibition of N-[3H]acetylglucosamine transfer from UDP-N-[3H]acetylglucosamine) while ongoing protein synthesis was not significantly modified (< 4% inhibition). In thyroid follicular cells, a regulatory link evidently exists between the synthesis of the peptide moiety of a glycoprotein and its glycosylation.