Regulation of the sodium iodide symporter by iodide in FRTL-5 cells

Abstract

Objective: The acute decrease in iodide organification in the thyroid in response to excess iodide is termed the acute Wolff±Chaikoff effect and normal organification resumes in spite of continued high plasma iodide concentrations (escape from the acute Wolff±Chaikoff effect). We have recently reported that large doses of iodide given to rats chronically decrease the sodium/iodide symporter (NIS) mRNA and protein, suggesting that escape is due to a decrease in NIS and subsequent iodide transport. We have now studied the effect of excess iodide on NIS in FRTL-5 cells to further explore the mechanisms whereby excess iodide decreases NIS. Design: FRTL-5 cells were employed and were incubated in the presence or absence of various concentrations of iodide. NIS mRNA and protein and the turnover of NIS were assessed. Methods: NIS mRNA was measured by Northern analysis, NIS protein by Western analysis and NIS turnover by pulse±chase labeling experiments. Results: Iodide (10 23 mol/l) had no effect on NIS mRNA in FRTL-5 cells at 24 and 48 h compared with cells cultured in the absence of iodide. However, excess iodide decreased NIS protein by 50% of control values at 24 h and by 70% at 48 h. This effect of iodide was dose dependent. Pulse±chase experiments demonstrated that there was no effect of iodide on new NIS protein synthesis and that the turnover of NIS protein in the presence of iodide was 27% faster than in the absence of added iodide. Conclusions: Excess iodide does not decrease NIS mRNA in FRTL-5 cells but does decrease NIS protein, suggesting that in this in vitro thyroid cell model iodide modulates NIS, at least in part, at a posttranscriptional level. This iodide-induced decrease in NIS protein appears to be due, at least partially, to an increase in NIS protein turnover.

A perspective view of sodium iodide symporter research and its clinical implications

“…The same group studied the effect of high doses of iodide on NIS regulation in FRTL-5 cells. Surprisingly, high doses of iodide during 24 and 48 h did not decrease the NIS mRNA levels, but did decrease the NIS protein levels in a dose-dependent manner, suggesting that in this in vitro thyroid cell model, iodide modulates NIS at a post-transcriptional level (22). These results are in sharp contrast with the previous in vivo study reported by the same authors.…”

Differentiated Thyroid Carcinoma That Express Sodium-Iodide Symporter Have a Lower Risk of Recurrence for Children and Adolescents

“…Expression of NIS is a marker of differentiated thyroid function, and at least some level of NIS expression is essential for successful therapy of thyroid carcinoma using radioactive iodine ablation (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). The utility of NIS immunostaining has been previously studied but only on a limited number of adult thyroid carcinomas.…”

“…NIS is essential for the uptake of iodide and thyroid hormone synthesis and is directly related to the level of thyroid differentiation (5-9). NIS expression is controlled by TSH and dependent on TTF-1 as well as [10][11][12][13][14][15]. Because of the central role of NIS in determining radioactive iodine uptake, it has been postulated that thyroid carcinoma that fail to express NIS would be resistant to radioactive iodine ablation (16).…”

Stimulation of iodide uptake by human chorionic gonadotropin in FRTL-5 cells: effects on sodium/iodide symporter gene and protein expression

“…These latter effects are likely to play an important role during pregnancy. Considering that many other factors, including iodide (30), estradiol (31,32) and certain cytokines (11,12), can also modify iodide uptake by acting on NIS expression, and that these factors are themselves subject to pregnancy related modifications, we feel that elucidation of the mechanisms that regulate NIS expression may help to clarify the pathogenesis of a number of thyroid disorders that are associated with pregnancy.…”