Thyroid hormone colloid

Figure 42-11. Model of iodide metabolism in the thyroid follicle. A follicular cell is shown facing the follicular lumen (top) and the extracellular space (at bottom). Iodide enters the thyroid primarily through a transporter (bottom left). Thyroid hormone synthesis occurs in the follicular space through a series of reactions, many of which are peroxidase-mediated. Thyroid hormones, stored in the colloid in the follicular space, are released from thyroglobulin by hydrolysis inside the thyroid cell. (Tgb, thyroglobulin MIT, monoiodotyrosine DIT, diiodotyro-sine Tj, triiodothyronine T4, tetraiodothyronine.) Asterisks indicate steps or processes that are inherited enzyme deficiencies which cause congenital goiter and often result in hypothyroidism.

Thyroglobulin A thyroid hormone-containing protein, usually stored in the colloid within the thyroid follicles. 

Thyroid hormones. Internally, the thyroid consists of follicles, which are spherical structures with walls formed by a single layer of epithelial cells called follicular cells. The center of each follicle contains a homogenous gel referred to as colloid. Thyroid hormones are stored here as a component of the larger molecule, thyroglobulin. The amount of thyroid hormones stored within the colloid is enough to supply the body for 2 to 3 months. 

Iodine, most ancient of the therapeutic agents for thyroid disorders, inhibits the secretion of thyroid hormone by retarding both the pinocyto-sis of colloid and proteolysis. This effect is observed in euthyroid as well as hyper thyroid persons. 

The first step in the release of thyroid hormones from the thyroid gland is through endocytosis of colloid from... 

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. 

The synthesis of T3, T4, DIT, and MIT in Tg molecules occurs mainly at the follicular ceU-colloid interface but also within the colloid. Tg is present m highest concentrations within the colloid, where it is stored. The follicular cells engulf colloid globules by endocytosis these globules then merge with lysosomes in the foUicular cell. Lysosomal proteases break the peptide bonds between iodinated residues and Tg, and T4, T3, DIT, and MIT are released into the cytoplasm of the follicular cell. T4 and T3 diffuse into the systemic circulation after their liberation from Tg. DIT and MIT are deiodinated by an intracellular microsomal iodoty-rosine dehalogenase. The freed iodide is then reused for thyroid hormone synthesis. 

Each step in the synthesis of thyroid hormones is regulated by pituitary TSH. TSH stimulates the iodide pump, Tg synthesis, and colloidal uptalce by foUicular cells. TSH also regulates the rate of proteolysis of Tg for the fib-eration of T4 and T3 is also regulated by TSH. In addition, TSH induces an increase in the size and number of the thyroid foUicular ceUs. Prolonged TSH stimulation leads to increased vascularity and eventual hypertrophic enlargement of the thyroid gland (goiter). 

The release of thyroid hormone following endocytosis of colloid is inhibited by iodide and is known to be reduced with high dietary intake of iodine. This inhibition is due to the inverse relationship between the iodide content of Tg and the digestibility of iodo-Tg by lysosomal peptidase that is, poorly iodinated Tg is more readily digested than richly iodinated Tg. 

Thyroglobulin is stored in the follicular lumen and must re-enter the cell, where the process of proteolysis liberates thyroid hormone into the bloodstream. Thyroid follicles active in hormone synthesis are identified histologically by columnar epithelial cells lining follicular lumens, which are depleted of colloid. Inactive follicles are lined by cuboidal epithelial cells and are replete with colloid. Both iodide and lithium block the release of preformed thyroid hormone, through poorly understood mechanisms. 

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. 

D. Thyroid hormones are synthesized from tyrosyl residues on thy-roglobuUn in the colloidal space of the thyroid foUicular cells. Although tyrosine can be obtained from the diet, it can also be synthesized from the essential amino acid phenylalanine by the action of phenylalanine hydroxylase. 

Thyroid hormone biosynthesis (Figure 45-2) involves the concentrative uptake of iodide into thyroid cells where it is converted into iodine by thyroid peroxidase in the colloid space of the folhcular lumen. Iodine is incorporated into tyrosine residues of thyroglobuhn contained within the colloid space at the basal surface of the thyroid follicular cell. Tyrosine residues are iodinated... 

Commercial PCB Mixtures. Various effects on the thyroid gland and thyroid hormone system have been observed in rats exposed to Aroclor 1254 by the oral route. Descriptions of the histological changes in the rat are reasonably consistent across studies. Typical findings, depending on the dose, include hyperplasia, hypertrophy, and increased vacuolization of follicular cells, depletion of follicular colloid and reduced follicular size, and thyroid enlargement (Collins and Capen 1980a Collins et al. 1977). 

BIOSYNTHESIS OF THYROID HORMONES The thyroid hormones are synthesized and stored as amino acid residues of thyroglobuUn, a complex glycoprotein that forms the bulk of thyroid folhcular colloid. The thyroid gland uniquely stores great quantities of potential hormone in this way, and extracellular thyroglobuUn can represent a large portion of the thyroid mass. 

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.

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 38.2 Possible sites of inhibitory actions of soy isoflavones on iodine utilization and thyroid hormone biosynthesis and actions. Soy isoflavonoids, genistein and daidzein, inhibit oxidation of iodide by thyroid peroxidase at the apical membrane of thyroid follicular cells, followed by iodination of tyrosine residues in thyroglobulin and their coupling in colloid. In addition, they may affect deiodination of iodothyronines and interfere with thyroid hormone binding to transthyretin. Full arrows indicate the sites of inhibition. So far, only few reports concern the effect of thyroid hormone actions in target cells.

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