Thyroid follicle cells

Thyroxine synthesis begins when iodide (I-) is transferred from the blood stream to the thyroid follicle cell by an active ATP-driven membrane pump mechanism this process is stimulated by cAMP following TSH stimulation of the gland. Iodide is transported through the follicular cell and secreted into the lumen of the follicle where it is oxidized to iodine and incorporated in to tyrosine residues by the enzyme thyroid peroxidase (TPO). 

The primary steps in thyroid hormone biosynthesis are shown schematically in Figure 31-2. Thyroid follicle cells take up and concentrate iodide from the bloodstream—this is significant because there must be a sufficient amount of iodine in the diet to provide what is needed for thyroid hormone production.55 Thyroid cells also manufacture a protein known as thy-... 

Iodide. Relatively large dosages of iodide (exceeding 6 mg/d) cause a rapid and dramatic decrease in thyroid function.35 In sufficient amounts, iodide inhibits virtually all the steps involved in thyroid hormone biosynthesis. For instance, high iodide levels limit the uptake of iodide into thyroid follicle cells, inhibit the formation of T4 and T3, and decrease the secretion of the completed hormones from the thyroid cell. 

Nilsson M, Engstrom G, Ericson LE (1986) Graded response in the individual thyroid follicle cell to increasing doses of TSH. Mol Cell Endocrinol 44 165-9 O Connor JC, Frame SR, Davis LG, Cook JC (1999) Detection of thyroid toxicants in a tier I screening battery and alterations in thyroid endpoints over 28 days of exposure. Toxicol Sci 51 54-70... 

Primary thyroid cells from rat, dog, pig, cow, sheep, and human have also been used for in vitro studies of thyroid follicle cells [70], They act similar to the cell lines described above in culture, and cultured conditions, media, and additives are the same. Fewer reagents are available for porcine or bovine cells however, thyroid tissue is fairly readily obtained and provides more cells than most common preclinical animals (e.g., rat, mouse). We have not detected T3 or T4 in culture medium of either porcine or bovine thyroid cells, but they respond to TSH or forskolin with concentration-dependent increases in intracellular levels of cAMP. Decreased expression of TSH-R and increased NIS and Tg expression were measured in the presence of TSH or forskolin (our unpublished data). 

Cytokeratin 7 (CK7) Adenocarcinoma of lung, GIT, pancreas, biliary tract, breast, endometrium, transitional cell carcinoma, serous ovarian tumors Merkel cell carcinoma, cloacogenic carcinoma Epithelium of GIT, salivary glands, biliary tract, pancreas, lung, female genital tract, renal collecting ducts transitional epithelium, mesothelial cells, thyroid follicle cells... 

Epithelium of GIT, salivary glands, biliary tract, pancreas, lung, female genital tract, transitional epithelium, mesothehal cells, thyroid follicle cells, basal squamous epithelium... 

Thyroglobuliii Thyroid tumors Thyroid follicle cells... 

K. Westermark, B. Westermark, F.A. Karlsson and L.E. Ericson, Location of Epidermal Growth Factor Receptors on Porcine Thyroid Follicle Cells and Receptor Regulation by Thyrotropin, Endorinology 118 1040 (1986). 

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.

There is no information existing about the exact stage when NIS and TPO, the two main targets for direct TGFD, become functional in zebrafish follicular cells. The presence of T4 in the first thyroid follicle at about 72 hpf suggests that both mechanisms are likely to be functional by that time. Moreover, exposing 48 hpf larvae... 

In some cases it is recommended to take radioactive iodine drugs such as iodotop (NaT ). It accumulates in the thyroid gland along with L-thyroxine and L-triiodothyronin, where radioactive decay takes place—weak 8-radiation destroys thyroid gland follicle cells, which leads to a gradual decline in thyroid hormone 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. 

Once taken up by the thyroid gland, iodide undergoes a series of enzymatic reactions that incorporate it into active thyroid hormone (Figure 38-1). The first step is the transport of iodide into the thyroid gland by an intrinsic follicle cell basement... 

FIGURE 31-2 Thyroid hormone biosynthesis. Iodide is taken into the follicle cell, where it is converted by thyroid peroxidase to an oxidized form of iodine (Ip). h is transported to the follicle lumen, where it is bonded to tyrosine residues of the thyroglobulin [TGB] molecule. Iodinated TGB is incorporated back into the cell, where it undergoes lysis to yield the thyroid hormones T3 and T4. See text for further discussion. 

The follicle cells, called thyrocytes, produce the thyroid hormones and are derived from the entodermal pharynx. Interspersed between follicles are specialized APUD cells derived from the neural crest, called C-cells or parafollicular cells. These cells produce calcitonin (CT), a polypeptide hormone discussed in Chapter 37. 

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. 

The elimination half-life of the drug is relatively short—around 5 hours. This is primarily caused by the uptake of the drug by thyroid follicular cells. This is also the reason for the relatively extended therapeutic half-life of the drug (> 40 hours)—once concentrated within follicular cells, it acts as an iodination substrate before degradation within the follicle. 

Oxidation and Iodination. The oxidation of iodide to its active form and the iodination of tyrosine are catalyzed by thyroid peroxidase, a heme-containing enzyme that utilizes hydrogen peroxide (HjOj) as the oxidant. The peroxidase is membrane-bound and concentrated at the apical surface of the thyroid cells. The reaction forms mono- and diiodotyrosyl residues in thyroglobulin just prior to its extracellular storage in the lumen of the thyroid follicle. is formed near its site of utilization and is stimulated by a rise in cytosolic Cd . ... 

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. 

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