Thyroid follicle

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. 

Fukayama H, Nasu M, Murakami S, et al. 1992. Examination of antithyroid effects of smoking products in cultured thyroid follicles only thiocyanate is a potent antithyroid agent. Acta Endocrinol (Copenh) 127(6) 520-525. 

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). 

Keywords Goitrogens, Thyroid follicle, Thyroid gland, Thyroid gland function dismptor, Thyroid hormone, Zebrafish... 

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... 

Fig. 2 Whole-mount T4 Immunofluorescence staining superposed on brightfield illumination of thyroid follicles in (a) 5 dpf control (0.1% DMSO used as a vehicle control), (b) 1.5 mM MMI-treated larvae, (c) 1 pM amiodarone-treated larvae, and (d) 50 nM T3-treated larvae. Heads of representative larvae are shown in ventral view with the anterior part on the left. Abbreviation e eye. Reprinted with permission from [46], Copyright 2009 American Chemical Society.

Fig. 3 Quantitative analysis of whole-mount T4-immunofluorescence signals for the Thyroxine Immunofluorescence Quantitative Disruption Test (TIQDT). The intrafollicular T4-content was calculated in the initial development of the TIQDT by measuring the average pixel intensity of the thyroid follicles. Reprinted with permission from [46],Copyright 2009 American Chemical Society.

In spite of the promising results obtained by using TIQDT, we found also some problems to be fixed. The main detected problems were (1) the variability in the size and number of thyroid follicles in each animal, (2) the fact that some TGFDs could impair the size or the number of thyroid follicles, but not the concentration/API of T4 signal inside of the quantified follicles, (3) some autofluorescence may be found with the set of immunofluorescence filters used, and (4) clear signs of systemic toxicity were found in eleutheroembryos exposed to some chemicals at the maximum tolerated concentration. For an optimized TIQDT protocol, we increased the... 

Wendl T, Lun K, Mione M, Eavor J, Brand M, Wilson SW et al (2002) Pax2.1 is required for development of thyroid follicles in zebrafish. Development 129 3751-3760... 

In older patients with goiter due to iodine deficiency there is a risk of provoking hyperthyroidism by increasing iodine intake (p. 247) During chronic maximal stimulation, thyroid follicles can become independent of TSH stimulation ( autonomic tissue"). If the iodine supply is increased, thyroid hormone production increases while TSH secretion decreases due to feedback inhibition. The activity of autonomic tissue, however, persists at a high level thyroxine is released in excess, resulting in iodine-induced hyperthyroidism. 

III.b.1.6. Radioactive iodine. Radioactive iodine (Iodine-131) is a radioactive isotope of iodine, usually taken in an oral solution formulation as sodium 1. Given orally as sodium I, radioactive iodine is rapidly absorbed, concentrated and stored in the thyroid follicles. The therapeutic effect depends on beta-ray emission and destruction of thyroid parenchyma manifests some weeks after treatment. It is relatively safe, cheap, painless and avoids side effects associated with surgery. It is widely regarded as the treatment of choice in adults with toxic multinodular goiter, toxic nodule and people who relapse after a course of antithyroid medication. 

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. 

Yamazaki K, Kanaji Y, Shizume K, Yamakawa Y, Demura H, Kanaji Y, Obara T, Sato K. Reversible inhibition by interferons alpha and beta of 125I incorporation and thyroid hormone release by human thyroid follicles in vitro. J Clin Endocrinol Metab 1993 77(5) 1439-41. 

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). 

Eales, J.G. Iodine metabolism and thyroid-related functions in organisms lacking thyroid follicles are thyroid hormones also vitamins Proc. Soc. Exp. Biol. Med. 214 302-317, 1997. 

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