Thyroglobulin function

Since OVA and BSA possess some immunologically similar epitopes, a population of the antibodies produced against one often will cross-react against the other. Therefore, OVA cannot function as a non-relevant carrier for BSA and vice versa. Either OVA or BSA, however, may be used as non-relevant carriers for KLH, thyroglobulin, or the various toxoid proteins used as immunogen conjugates. 

Thyrotoxicosis factitia should be suspected in a thyrotoxic patient without evidence of increased hormone production, thyroidal inflammation, or ectopic thyroid tissue. The RAIU is low because thyroid gland function is suppressed by the exogenous thyroid hormone. Measurement of plasma thyroglobulin reveals the presence of very low levels. 

Fig. 1 Thyroid hormone synthesis in a thyroid follicular cell. NIS and TPO (organification and coupling reaction) have been marked in red dashed line as the two main targets for direct thyroid gland function disrupters. DEHALl iodotyrosine dehalogenase 1, DIT diiodotyrosine, DUOX2 dual oxidase 2, MIT monoiodotyrosine, Na/K-ATPase sodium-potassium ATPase, NIS sodium-iodide symporter, PSD pendrin, TG thyroglobulin, TPO thyroperoxidase. Reprinted from [7] with permission from Elsevier...

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. 

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. 

Lithium affects thyroid function (52-56), and in most patients, after 4 months of treatment, there is a transient fall in serum levels of thyroxine (T4) and a rise in thyrotropic hormone (thyroid-stimulating hormone, TSH). After 1 year of treatment, these hormones have generally returned to their baseline. The mechanisms for this are obscure, but lithium inhibits both thyroxine synthesis and its release from the gland (201). Lithium may inhibit endocytosis in the thyroid gland, which results in an accumulation of colloid and thyroglobulin within the follicles, thereby reducing hormone release (202). Thyroid volume... 

The expression of the sodium iodide symporter is perhaps nowhere more important than in the thyroid gland. A complete review of the physiological importance of the thyroid is beyond the scope of this chapter. It is sufficient to say that the symporter provides the iodine needed for normal thyroid function. Once the symporter has been trafficked to the basolateral surface of the thyrocyte, it can transport iodine from the blood into the cell. Once inside the cells, iodine is transported to the apical membrane where it is organified through attachment to a tyrosine residue and incorporated into the thyroid hormone thyroglobulin. The thyroglobu-lin is then stored inside thyroid follicles as colloid, to be released into the bloodstream as thyroid hormones (thyroxine and triiodothyronine) via TSH stimulation. 

Figure 32.3 Inhibitory effects of iodide on human thyrocytes function, r, iodide NiS, sodium iodide symporter DUOX, duai oxidase TPO, thyroperoxidase TG, thyroglobulin TGI, iodinated thyroglobuiin X, the substrate converted into the active inhibitory iodinated molecule XI micro, micropinocytosis macro, macropinocytosis prolif, proliferation G.I., gene induction R, receptor Gs, stimulatory G protein of adenylyl cyclase AC, adenylyl cyclase cAMP, cyclic 3 -5 adenosine monophosphate PGE, prostaglandin E1 NE, norepinephrine Gq, stimulatory G protein of phospholipase C DAG, diacylglycerol IPS, inositol 1,4,5-trisphosphate Aa, amino acid ...

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