Nh2

FIGURE 5 Hypothetical coupling scheme for intramolecular formation of T4 based on model reaction with purified thyroid peroxidase. (From Taurog A. in Braverman LE, Utiger RD, eds., Werner's the thyroid, 8th ed., Philadelphia: Lippincott Williams and Wilkins, p. 71.)

vesicles (Fig. 6). In chronic situations uptake is probably less dramatic than that shown in Fig. 6, but nevertheless requires an ongoing endocytic process. The endocytic vesicles migrate toward the basal portion of the cells and fuse with lysosomes, which simultaneously migrate from the basal to the apical region of the cells to meet the incoming endocytic vesicles. As fused lysoendosomes migrate toward the basement membrane, thyroglobulin is degraded to peptide fragments and free amino acids, including T4, T3, MIT, and DIT. Of these, only T4 and T3 are released into the bloodstream, in a ratio of about 20:1, perhaps by a process of simple diffusion down a concentration gradient.

39. Thyroid Gland

FIGURE 6 Scanning electron micrographs of the luminal microvilli of dog thyroid follicular cells. (A) TSH secretion suppressed by feeding thyroid hormone. (B) At 1 hr after TSH. A, 36,000x; B, 16,500x. (From Balasse PD, Rodesch FR, Neve PE, et al. Observations en microscopie a balayage de la surface apicale y de cellules folliculares thyroidiennes chez le chien. C Roy Acad Sci [D] (Paris), 1972;274:2332.)

Monoiodotyrosine and DIT cannot be utilized for synthesis of thyroglobulin and are rapidly deiodinated by a specific microsomal deiodinase. Virtually all of the iodide released from iodotyrosines is recycled into thyroglobulin. Deiodination of iodotyrosine provides about twice as much iodide for hormone synthesis as the iodide pump and is therefore of great significance in hormone biosynthesis. Patients who are genetically deficient in thyroidal tyrosine deiodinase readily suffer symptoms of iodine deficiency and excrete MIT and DIT in their urine. Normally, virtually no MIT or DIT escape from the gland.

Synthesis of thyroglobulin and its export in vesicles into the follicular lumen is an ongoing process that takes place simultaneously with uptake of thyroglobulin in other vesicles moving in the opposite direction. These opposite processes, involving vesicles laden with thyro-globulin moving into and out of the cells, are somehow regulated so that under normal circumstances thyro-globulin neither accumulates in the cells or follicular lumens nor is depleted. The physiologic mechanisms for such traffic control are not yet understood.

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