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L. LAMAS, S. H. INGBAR, The Effect of Varying Iodine Content on the Susceptibility of Thyroglobulin to Hydrolysis by Thyroid Acid Protease, Endocrinology, Volume 102, Issue 1, 1 January 1978, Pages 188–197, https://doi.org/10.1210/endo-102-1-188
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To examine the mechanism whereby iodine inhibits the proteolysis of thyroglobulin (Tgb) and hormone release, hydrolysis of Tgb preparations of varying iodine content by a standardized hog thyroid particulate fraction (P20) was studied. Rats receiving low iodine diet plus iodine supplements were given 125I 72 and 48 h and 131I 3 h before death. Tgb was purified by sucrose density gradient centrifugation and incubated with P20 at pH 3.7 for varying periods. The extent and products of hydrolysis were assessed by paper chromatography. As expected, iodine-rich Tgb contained greater proportions of thyroxine and diiodotyrosine and lower proportions of triiodothyronine and monoiodotyrosine than did iodine-poor Tgb. Hydrolysis was consistently slower in iodine-rich than in iodine-poor Tgb and was accelerated in both by reduced glutathione (1–2 × 10-3 M), especially in the iodine-rich Tgb. In iodine-rich Tgb, [131I]iodoamino acids (new label) consistently were released slightly faster than [125I]iodoamino acids (old label); this difference was less consistently seen in iodine-poor Tgb.
Dietary supplements of 10 μg iodine/day significantly increased both the iodine content of Tgb and its resistance to proteolysis by P20, but larger supplements had no further effect on either iodine content or resistance to proteolysis of the isolated Tgb. Enrichment of iodinepoor Tgb by a single acute injection of iodide 3 h before death also decreased the susceptibility of Tgb to hydrolysis. In vitro, inorganic iodide had no effect.
The data indicate that in vivo iodination of iodinepoor Tgb renders it less susceptible to hydrolysis by the thyroid acid protease. This effect probably results largely from increased disulfide bonding, but configurational changes secondary to increased coupling may also play a role. The more rapid hydrolysis of iodine-poor Tgb may provide an efficient mechanism for accelerating hormone release from the iodine-deficient thyroid. Conversely, the resistance to hydrolysis of iodine-rich Tgb may partly explain the inhibitory effect of iodine on thyroid hormone release in some states. (Endocrinology102: 188, 1978)
