Iodine Suppression of Iodide Uptake in FRTL-5 Thyroid Cells

Grollman, Evelyn F.; Smolar, Andrew I.; A, Ommaya; Tombaccini, Donatella; Santisteban, Pilar

doi:10.1210/endo-118-6-2477

Cited by 59 publications

(36 citation statements)

References 26 publications

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“…NaI treatment is unable to reduce radioiodide transport when TPO activity was concomitantly inhibited by MMI administration, showing that NIS function is reduced by iodide only when TPO activity is present. These results support the idea that organified iodine (IX) rather than iodide itself is responsible for the inhibition of the basolateral transport of I -, as previously suggested (29). The iodinated compounds that are candidates for iodine organification blockade are iodolipids (iodohexadecanal and iodolactones) (30,31).…”

Section: Regulation Of Expression and Function In Thyroid Cellssupporting

confidence: 86%

The importance of sodium/iodide symporter (NIS) for thyroid cancer management

Carvalho

Ferreira

2007

Arq Bras Endocrinol Metab

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The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124 I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors. A glândula tireóide tem capacidade de captar e concentrar iodeto, etapa fundamental na biossíntese dos hormônios tireóideos. O uso de iodo radioativo para fins de diagnóstico e terapia das doenças da tireóide vem sendo feito há muitos anos. Entretanto, somente após a clonagem do gene que codifica o cotransportador de sódio/iodeto (NIS) houve aumento significativo dos estudos relacionados ao mecanismo de transporte de iodeto. Os estudos sobre a regulação da expressão do NIS e a possibilidade de terapia gênica visando à transferência do gene NIS para células que normalmente não expressam esse transportador, foram também viabilizados. Na maior parte dos nódulos tireóideos hipofuncionantes, tanto benignos quanto malignos, a expressão do gene do NIS está presente, mas a proteína NIS fica retida no compartimento intracelular. A transferência do gene usando-se promotores tecido-específicos possibilitou a expressão do NIS em células tumorais não-tireóideas in vivo. Além do seu uso terapêutico, o NIS também vem sendo usado para a localização de metástases tumorais através da cintilografia ou do PET-scan usando-se 124 I. Em conclusão, a clonagem do NIS possibilitou enorme avanço na área de fisiopatologia tireóidea e foi também fundamental para estender o uso do radioiodo para tumores não tireóideos.

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Section: Regulation Of Expression and Function In Thyroid Cellssupporting

confidence: 86%

The importance of sodium/iodide symporter (NIS) for thyroid cancer management

Carvalho

Ferreira

2007

Arq Bras Endocrinol Metab

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“…Another fact to be highlighted is that the inhibitory effect promoted by iodide excess on the thyroid gland has been ascribed to the iodolipids production by TPO (17,20). In fact, we cannot exclude the possibility of a role of iodolipid production in the regulation of NIS gene expression, because a higher reduction of NIS mRNA content was observed after iodide excess administration in rats that did not undergo .…”

Section: Discussionmentioning

confidence: 90%

Posttranscriptional regulation of sodium-iodide symporter mRNA expression in the rat thyroid gland by acute iodide administration

Serrano‐Nascimento

Calil-Silveira

Nunes

2010

American Journal of Physiology-Cell Physiology

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Serrano-Nascimento C, Calil-Silveira J, Nunes MT. Posttranscriptional regulation of sodium-iodide symporter mRNA expression in the rat thyroid gland by acute iodide administration. Am J Physiol Cell Physiol 298: C893-C899, 2010. First published January 27, 2010 doi:10.1152/ajpcell.00224.2009Iodide is an important regulator of thyroid activity. Its excess elicits the Wolff-Chaikoff effect, characterized by an acute suppression of thyroid hormone synthesis, which has been ascribed to serum TSH reduction or TGF-␤ increase and production of iodolipids in the thyroid. These alterations take hours/days to occur, contrasting with the promptness of WolffChaikoff effect. We investigated whether acute iodide administration could trigger events that precede those changes, such as reduction of sodium-iodide symporter (NIS) mRNA abundance and adenylation, and if perchlorate treatment could counteract them. Rats subjected or not to methylmercaptoimidazole treatment (0.03%) received NaI (2,000 g/0.5 ml saline) or saline intraperitoneally and were killed 30 min up to 24 h later. Another set of animals was treated with iodide and perchlorate, in equimolar doses. NIS mRNA content was evaluated by Northern blotting and real-time PCR, and NIS mRNA poly(A) tail length by rapid amplification of cDNA ends-poly(A) test (RACE-PAT). We observed that NIS mRNA abundance and poly(A) tail length were significantly reduced in all periods of iodide treatment. Perchlorate reversed these effects, indicating that iodide was the agent that triggered the modifications observed. Since the poly(A) tail length of mRNAs is directly associated with their stability and translation efficiency, we can assume that the rapid decay of NIS mRNA abundance observed was due to a reduction of its stability, a condition in which its translation could be impaired. Our data show for the first time that iodide regulates NIS mRNA expression at posttranscriptional level, providing a new mechanism by which iodide exerts its autoregulatory effect on thyroid.NIS mRNA poly(A) tail; RACE-PAT; perchlorate THERE IS A GROWING body of evidence showing that trace elements, such as iron and selenium, modify the expression of proteins that are involved in their transport and metabolism by posttranscriptionally regulating the expression of the mRNAs that encode them. This posttranscriptional regulation mechanism rapidly changes gene expression patterns and occurs mainly at the transcript polyadenylation level, leading to alterations of the mRNA poly(A) tail length, which has been directly associated to transcript stability and translation efficiency (1-3, 34).Iodine is known to acutely regulate the expression of the sodium-iodide symporter (NIS), a specific protein present in the basement membrane of thyroid cells and that mediates iodide uptake (8). This trace element is essential for thyroid hormone synthesis, although its excess causes a blockade of the thyroid function, which is known as the Wolff-Chaikoff effect (29,49). This effect is rapid and transitory, and the mechanisms ...

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“…This phenomenon shows that the Wolff-chaikoff effect may be mediated by intracellular or follicular iodinated compounds, such as iodine lipids, which have been confirmed to inhibit TSH-mediated adenylate cyclase activity (16,17).…”

Section: Introductionmentioning

confidence: 87%

Intracellular iodinated compounds affect sodium iodide symporter expression through TSH-mediated signaling pathways

et al. 2010

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Abstract.The mechanisms by which thyroid stimulating hormone (TSH) regulates the expression and activity of sodium iodide symporter (niS) through caMP-PKa have been partially elucidated by many studies. However, the effects of the TSH-mediated Plc-iP3 signaling pathway on the expression of niS and how intracellular iodinated compounds interfere with these signaling pathways are poorly understood. in this study, we investigated the effects of the TSH-mediated caMP-PKa and Plc-iP3 pathways on the expression of niS in the presence of various intracellular iodinated compounds. The intracellular iodinated compounds were formed by treating cells with different concentrations of iodine with or without methimazole (MMi), an inhibitor of iodine organification, in a pig monolayer thyrocyte in vitro. a high concentration of iodine increased niS expression at the mrna and protein levels; however, this phenomenon was not observed in the presence of MMi. Both the caMP-PKa and Plc-iP3 signaling pathways inhibited the expression of niS at low iodine concentrations; however, in thyrocytes treated with high concentrations of iodine, the effect of caMP-PKa on the expression of niS changed from inhibition to promotion, while the Plc-iP3 pathway continued to inhibit niS expression. These findings indicate that intracellular iodinated compounds affect niS expression through the TSH-mediated caMP-PKa and Plc-iP3 pathways.

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Iodine Suppression of Iodide Uptake in FRTL-5 Thyroid Cells

Cited by 59 publications

References 26 publications

The importance of sodium/iodide symporter (NIS) for thyroid cancer management

The importance of sodium/iodide symporter (NIS) for thyroid cancer management

Posttranscriptional regulation of sodium-iodide symporter mRNA expression in the rat thyroid gland by acute iodide administration

Intracellular iodinated compounds affect sodium iodide symporter expression through TSH-mediated signaling pathways

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