Thyroglobulin secretion

Thyroid epithelial cells synthesize and secrete T4 and T3 and make up the functional units of thyroid glandular tissue, the thyroid follicles. Thyroid follicles are hollow vesicles formed by a single layer of epithelial cells that are filled with colloid. T4,T3, and iodine are stored in the follicular colloid. T4 and T3 are derived from tyrosyl residues of the protein thyroglobulin (Tg). Thyroid follicular cells synthesize and secrete Tg into the follicular lumen. Thyroid follicular cells also remove iodide (I ) from the blood and concentrate it within the follicular lumen. Within the follicles, some of the tyrosyl residues of Tg are iodinated, and a few specific pairs of iodoty-rosyl residues may be coupled to form T4 and T3. Thus, T4, T3, and iodine (in the form of iodinated tyrosyl residues) are found within the peptide structure of the Tg that is stored in the follicular lumen. 

Thyroxine (T4) and the more potent triiodothyronine (T3) are cleaved from a large precursor protein called thyroglob-ulin. Thyroglobulin exists as a dimer of two identical polypeptides (Mr 330,000). It is a storage protein for iodine and can be considered a prohormone of the circulating thyroid hormones. Thyroglobulin is secreted into the lumen of the thyroid gland, where specific residues are iodinated in... 

The secretion of thyroid hormones starts with endocy-tosis of the modified thyroglobulin, followed by fusion of the endocytotic vesicles with lysosomes. The lysosomal enzymes then degrade the thyroglobulin, liberating triiodothyronine and thyroxine into the circulation. Only about five molecules of T3 and T4 are generated from each molecule of thyroglobulin. Thyroid hormone secretion is stimulated by thyrotropin (TSH), a pituitary hormone that activates adenylate cyclase in its target cells. 

Radioactive isotopes of iodine are handled by the thyroid in the same way as stable iodine and are therefore actively concentrated, incorporated into thyroglobulin, stored, metabolized, and secreted as thyroid hormones. Small amounts of radioactive iodine are therefore ideal probes to analyse the uptake of iodine, the distribution of iodine in the gland, and possibly even its turnover and incorporation into thyroid hormones. Larger amounts of radioactive iodine selectively radiate the thyroid gland and therefore selectively impair the function of the follicular thyroid cells and eventually destroy them. 

The iodinated thyroglobulin is stored as a colloid in thyroidal follicular cells, and T3 and T4 are liberated from it by proteolysis as required. It is estimated that ca 90 Jig of T4 and 6 Jig of T3 are secreted daily by the thyroid gland, giving mean plasma concentrations of 80 and 2 lg/L, respectively, of which only 0.03 and 0.3% are in the free form, ie, not protein bound (21). The half-life of T4 in the body is long (6—7 d) (2) that of T3 is somewhat shorter... 

The thyroid gland is made up of multiple follicles that consist of a single layer of epithelial cells surrounding a lumen filled with colloid (thyroglobulin), the storage form of thyroid hormone. A diagram of the steps in thyroid hormone synthesis and secretion is shown in Figure 25.6. 

Correct answer = O. Propylthiouracil blocks the synthesis of the thyroid hormones, but does not affect the uptake of iodide, proteolytic cleavage of thyroglobulin, or the release of hormones from the thyroid gland. The thyroid hormones inhibit the secretion of thyroid-stimulating hormone from the anterior pituitary. ... 

G. Medeiros-Neto, H. M. Targovnik, and G. Vassart Defective thyroglobulin synthesis and secretion causing goiter and hypothyroidism. Endocrine Review 14, 165 (1993). 

FIGURE 73-2. Thyroid hormone synthesis. Iodide is transported from the plasma, through the cell, to the apical membrane where it is organified and coupled to the thyroglobulin (TG) synthesized within the thyroid cell. Hormone stored as colloid re-enters the cell through endocytosis and moves back toward the basal membrane, where T4 is secreted. 

Thyroglobulin (TG). This glycoprotein secreted by thyroid follicular cells is a major autoantigen in autoimmune thyroid diseases. Thyroglobulin autoantibodies were found in patients with autoimmune thyroiditis ( - thyroiditis, autoimmune) and Graves disease. 

The first measurable effect of TSH on thyroid hormone metabolism is increased secretion, which is detectable within minutes. AU phases of hormone synthesis and secretion are eventually stimulated iodide uptake and organification, endocytosis, and proteolysis of thyroglobulin. There also is increased vascularity of the gland and hypertrophy and hyperplasia of thyroid cells. 

Fig. 43.10. Synthesis of the thyroid hormones (T3 and T4). The protein thyroglobulin (Tgb) is synthesized in thyroid follicular cells and secreted into the colloid, lodination and coupling of tyrosine residues in Tgb produce T3 and T4 residues, which are released from Tgb by pinocytosis (endocytosis) and lysosomal action. The coupling of a monoiodotyrosine with a diiodotyrosine (DIT) to form triiodothyronine (Tj) is not depicted here.

Fig. 34.2. Summary of the major pathways for the biosynthesis and secretion of the thyroid hormones. When thyrotropin (TSH) binds to the TSH receptor at the basal membrane of the follicular cell, the biosynthesis of thyroglobulin (TG) is stimulated, as is that of thyroperoxidase (TPO) and the production of hydrogen peroxide. Noniodinated TG is synthesized by the rough endoplasmic reticulum of the follicular cell and secreted through the apical membrane of the follicular cell into the follicular lumen. Iodide enters the follicular cell by the iodide pump (NIS, sodium iodide symporter) and is then transported into the follicular lumen. In the lumen, the iodide is oxidized by TPO-O (a Ti-cation radical intermediate formed from TPO and hydrogen peroxide) at the apical...

Although shown as a sequential reaction, the iodination and coupling reactions occur simultaneously via TPO and hydrogen peroxide. Hydrogen peroxide is generated by a NADPH/FAD thyroid oxidase (THOX) at the apical membrane. Low plasma levels for T4 cause the iodinated TG to be resorbed into the follicular cell, where complete proteolysis occurs by lysosomal protease to T4, T3, DIT, MIT, and noniodinated amino acids. Both T4 and T3 are secreted by the cell into the blood T4 is deiodinated to active T3. Both DIT and MIT are recycled by a dehalogenase (or deiodinase) to free tyrosine and iodide, both of which are recycled back into iodinated thyroglobulin. 

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