The relative roles of iodination and iodothyronine content on thyroglobulin stability.

We have independently varied the degree of iodination and of iodothyronine formation over a wide range by acutely administering various doses of perchlorate and/or methimazole to severely iodine-deficient rats 30 min before giving 131-I- with graded quantities (1-100 mug of 127-I-). Thyroids were removed 4 h later and the soluble protein analyzed for labelled iodoamino acid composition and with sucrose density gradient ultracentrifugation. Since the total thyroid iodine content before administering 127I- was less than 1 mug, calculation of the degree of iodination and iodothyronine content of the labelled Tgb could be made from the known specificity of the injected labelled iodide. Newly organified iodine ranged from smaller than 0.1 to 1.4 mug/thyroid and labelled iodothyronines from smaller than 5 to 962 pmoles/thyroid. Both the degree of iodination and iodothyronine content varied directly with Tgb stability in the absence of inhibitors. But when Tgb iodination was kept constant, Tgb stability at pH 10.1 varied directly with iodothyronine content. When iodothyronine content was kept constant, Tgb stability was independent of the degree of iodination. Correlation of stability with iodothyronine content was highly significant (r=0.79, Psmaller than 0.001) but not of stability with iodine content (r=0.49, P larger than 0.05). We conclude that the primary determinant of Tgb stability in mild alkali is the iodothyronine content and not the degree of iodination of the protein. The increased Tgb stability may be induced by coupling between iodotyrosil residues of different 12 S subunits rather than between residues of the same 12 S subunit.