Iodide thyroid uptake

What is the basic mechanism of action of thiocyanate in inhibiting iodide uptake by the thyroid gland ... 

C) Thiocyanate competitively inhibits iodide uptake by the thyroid follicular cells. 

C. Thiocyanate and other monovalent anions, such as perchlorate, inhibit iodide uptake by acting as competitive inhibitors of iodide uptake by the thyroid follicular cells. This is the only relevant action of these anions in this situation. 

The thyroid gland also regulates its uptake of iodide and thyroid hormone synthesis by intrathyroidal mechanisms that are independent of TSH. These mechanisms are primarily related to the level of iodine in the blood. Large doses of iodine inhibit iodide organification (Wolff-Chaikoff block, see Figure 38-1). In certain disease states (eg, Hashimoto s thyroiditis), this can inhibit thyroid hormone synthesis and result in hypothyroidism. Hyperthyroidism can result from the loss of the Wolff-Chaikoff block in susceptible individuals (eg, multinodular goiter). 

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. 

In thyroid cells in culture, ceilcitriol reduces production of cAMP in response to thyr oid stimulating hormone by a nuclear- action on the synthesis of G-protein subunits. However, it also reduces the responsiveness to cAMP, emd attenuates cell growth and iodide uptake in response to thyroid stimulating hormone, with a rapid time course from direct action on protein kinase A (Berg andHaug, 1999). 

FIGURE 18.14 Iodide uptake, transport, metabolism, and salvage in thyroid follicular cells. (Adapted from Rokita, Adler, McTarrmey, Watson, 2010.)... 

Iodide Uptake and Gene Expression as Endpoints in Thyroid Cell Models... 

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... 

Three- to four-day old northern bobwhite were used to evaluate the influence of ammonium perchlorate (AP) on thyroid function, as well as thyroidal hormone level systemic effects on the hypothalamic-pituitary-thyroid axis [46], The perchlorate ion competitively inhibits iodide uptake, thus with time AP has the potential to reduce... 

Uptake of Iodide. Dietary iodine reaches the circulation as iodide. Normally, its concentration in the blood is very low (0.2-0.4 ag/dL about 15-30 uM), but the thyroid actively transports the ion via a specific, membrane-bound protein termed the sodium-iodide symporter (NIS). The ratio of thyroid to plasma iodide concentration is usually between 20 and 50 and can far exceed 100 when the gland is stimulated. The NIS is inhibited by a number of ions such as thiocyanate and perchlorate (Figure 56-3). Thyrotropin (see below) stimulates the NIS, which is controlled by an autoregulatory mechanism. Thus, decreased stores of thyroid iodine enhance iodide uptake, and the administration of iodide can reverse this situation by decreasing NIS protein expression. 

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. 

Histone deacetylase inhibitors, depsipeptide (FR901228), trichostatin A (TSA), and valproic acid, increase NIS expression in thyroid cancer cell lines (Kitazono et al., 2001 Kogai et al., 2006). Depsipeptide significantly induces NIS mRNA and iodide uptake in follicular thyroid cancer cell lines (FTC 133 and FTC 236) and two anaplastic cancer cell lines (SW-1736 and KAT-4) at a low concentration (Ing/ml) in vitro (Kitazono et al., 2001). Pharmacokinetics of depsipeptide in patients have indicated that levels of more than 500ng/ml are... 

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