scholarly journals Effect of Iodide on Human Choriogonadotropin, Sodium-Iodide Symporter Expression, and Iodide Uptake in BeWo Choriocarcinoma Cells

2007 ◽  
Vol 92 (10) ◽  
pp. 4046-4051 ◽  
Author(s):  
Huika Li ◽  
Kerry Richard ◽  
Brett McKinnon ◽  
Robin H. Mortimer
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Mrna Expression ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Hormone Synthesis ◽  
Human Choriogonadotropin ◽  
Fetal Thyroid ◽  
Choriocarcinoma Cells

Abstract Context: Active placental transport of maternal iodide by the thyroidal sodium iodide symporter (NIS) provides an essential substrate for fetal thyroid hormone synthesis. NIS is expressed in trophoblast and is regulated by human choriogonadotropin (hCG). In thyroid, iodide down-regulates expression of several genes including NIS. Placentas of iodine-deficient rats demonstrate up-regulation of NIS mRNA, suggesting a role for iodide in regulating placental NIS. Objectives and Methods: The objectives were to examine effects of iodide on expression of NIS and hCG in BeWo choriocarcinoma cells. Gene expression was studied by quantitative real-time PCR. Effects on NIS protein expression were assessed by Western blotting. Functional activity of NIS was measured by 125I uptake. Expression of hCG protein was assessed by immunoassay of secreted hormone. Results: Iodide inhibited NIS mRNA and membrane protein expression as well as 125I uptake, which were paralleled by decreased βhCG mRNA expression and protein secretion. Iodide had no effects on pendrin expression. Addition of hCG increased NIS mRNA expression. This effect was partially inhibited by addition of iodide. The inhibitory effects of iodide on NIS mRNA expression were abolished by propylthiouracil and dithiothreitol. Conclusions: We conclude that expression of placental NIS is modulated by maternal iodide. This may occur through modulation of hCG effects on NIS and hCG gene expression.

scholarly journals Propylthiouracil increases sodium/iodide symporter gene expression and iodide uptake in rat thyroid cells in the absence of TSH

Thyroid ◽  
2012 ◽  
pp. 120521124804007
Author(s):  
Sue Mariko ◽  
Takeshi Akama ◽  
Akira Kawashima ◽  
Hannah Nakamura ◽  
Takeshi Hara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Rat Thyroid

scholarly journals Iodide excess regulates its own efflux: a possible involvement of pendrin

2016 ◽  
Vol 310 (7) ◽  
pp. C576-C582 ◽  
Author(s):  
Jamile Calil-Silveira ◽  
Caroline Serrano-Nascimento ◽  
Peter Andreas Kopp ◽  
Maria Tereza Nunes
Keyword(s):  
Plasma Membrane ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Sodium Iodide ◽  
Inhibitory Effect ◽  
Membrane Insertion ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Hormone Synthesis ◽  
Rat Thyroid

Adequate iodide supply and metabolism are essential for thyroid hormones synthesis. In thyrocytes, iodide uptake is mediated by the sodium-iodide symporter, but several proteins appear to be involved in iodide efflux. Previous studies demonstrated that pendrin is able to mediate apical efflux of iodide in thyrocytes. Acute iodide excess transiently impairs thyroid hormone synthesis, a phenomenon known as the Wolff-Chaikoff effect. Although the escape from this inhibitory effect is not completely understood, it has been related to the inhibition of sodium-iodide symporter-mediated iodide uptake. However, the effects of iodide excess on iodide efflux have not been characterized. Herein, we investigated the consequences of iodide excess on pendrin abundance, subcellular localization, and iodide efflux in rat thyroid PCCl3 cells. Our results indicate that iodide excess increases pendrin abundance and plasma membrane insertion after 24 h of treatment. Moreover, iodide excess increases pendrin half-life. Finally, iodide exposure also increases iodide efflux from PCCl3 cells. In conclusion, these data suggest that pendrin may have an important role in mediating iodide efflux in thyrocytes, especially under conditions of iodide excess.

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

2010 ◽  
Vol 298 (4) ◽  
pp. C893-C899 ◽  
Author(s):  
Caroline Serrano-Nascimento ◽  
Jamile Calil-Silveira ◽  
Maria Tereza Nunes
Keyword(s):  
Mrna Expression ◽  
Posttranscriptional Regulation ◽  
Sodium Iodide ◽  
Tail Length ◽  
Northern Blotting ◽  
Mrna Abundance ◽  
Translation Efficiency ◽  
Sodium Iodide Symporter ◽  
Hormone Synthesis ◽  
Rat Thyroid

Iodide 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-β increase and production of iodolipids in the thyroid. These alterations take hours/days to occur, contrasting with the promptness of Wolff-Chaikoff 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 μg/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.

scholarly journals Cloning of the mouse sodium iodide symporter and its expression in the mammary gland and other tissues

2001 ◽  
Vol 170 (1) ◽  
pp. 185-196 ◽  
Author(s):  
B Perron ◽  
AM Rodriguez ◽  
G Leblanc ◽  
T Pourcher
Keyword(s):  
Mammary Gland ◽  
Mammalian Cells ◽  
Sodium Iodide ◽  
Distribution Analysis ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Reading Frame ◽  
Hormone Synthesis ◽  
Iodide Transport ◽  
Lactating Mammary Gland

Iodide concentration in milk by mammals is a necessary step for thyroid hormone synthesis by the newborn. With the purpose of using the mouse as an animal model to analyse the role of the sodium iodide symporter (NIS) in iodide transport and its regulation in the mammary gland, mouse NIS (mNIS) cDNA was isolated from lactating mice. The cloned sequence shows an open reading frame of 1854 nucleotides encoding a protein of 618 amino acids highly homologous to the rat and human NIS (95% and 81% identity respectively). Expression of mNIS in cultured mammalian cells induced cellular iodide accumulation. This iodide uptake process is sodium dependent and inhibited by thiocyanate and perchlorate. Tissue distribution analysis revealed that mNIS mRNAs are predominantly expressed in thyroid, stomach and in the lactating mammary gland and are present to a lower extent in several other tissues. Our data show for the first time that the level of mNIS mRNA is upregulated in the mammary gland during lactation.

scholarly journals Hydrocortisone and Purinergic Signaling Stimulate Sodium/Iodide Symporter (NIS)-Mediated Iodide Transport in Breast Cancer Cells

2006 ◽  
Vol 20 (5) ◽  
pp. 1121-1137 ◽  
Author(s):  
Orsolya Dohán ◽  
Antonio De la Vieja ◽  
Nancy Carrasco
Keyword(s):  
Breast Cancer ◽  
Thyroid Cancer ◽  
Protein Expression ◽  
Therapeutic Efficacy ◽  
Sodium Iodide ◽  
Purinergic Signaling ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Mcf 7

Abstract The sodium/iodide symporter (NIS) mediates a remarkably effective targeted radioiodide therapy in thyroid cancer; this approach is an emerging candidate for treating other cancers that express NIS, whether endogenously or by exogenous gene transfer. Thus far, the only extrathyroidal malignancy known to express functional NIS endogenously is breast cancer. Therapeutic efficacy in thyroid cancer requires that radioiodide uptake be maximized in tumor cells by manipulating well-known regulatory factors of NIS expression in thyroid cells, such as TSH, which stimulates NIS expression via cAMP. Similarly, therapeutic efficacy in breast cancer will likely depend on manipulating NIS regulation in mammary cells, which differs from that in the thyroid. Human breast adenocarcinoma MCF-7 cells modestly express endogenous NIS when treated with all-trans-retinoic acid (tRa). We report here that hydrocortisone and ATP each markedly stimulates tRa-induced NIS protein expression and plasma membrane targeting in MCF-7 cells, leading to at least a 100% increase in iodide uptake. Surprisingly, the adenyl cyclase activator forskolin, which promotes NIS expression in thyroid cells, markedly decreases tRa-induced NIS protein expression in MCF-7 cells. Isobutylmethylxanthine increases tRa-induced NIS expression in MCF-7 cells, probably through a purinergic signaling system independent of isobutylmethylxanthine’s action as a phosphodiesterase inhibitor. We also observed that neither iodide, which at high concentrations down-regulates NIS in the thyroid, nor cAMP has a significant effect on NIS expression in MCF-7 cells. Our findings may open new strategies for breast-selective pharmacological modulation of functional NIS expression, thus improving the feasibility of using radioiodide to effectively treat breast cancer.

scholarly journals Expression of sodium-iodide symporter mRNA in the thyroid gland of Xenopus laevis tadpoles: developmental expression, effects of antithyroidal compounds, and regulation by TSH

2006 ◽  
Vol 190 (1) ◽  
pp. 157-170 ◽  
Author(s):  
Robert Opitz ◽  
Achim Trubiroha ◽  
Claudia Lorenz ◽  
Ilka Lutz ◽  
Sabine Hartmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Gland ◽  
Xenopus Laevis ◽  
Mrna Expression ◽  
Sodium Iodide ◽  
Developmental Expression ◽  
Intracellular Camp ◽  
Sodium Iodide Symporter ◽  
Thyroid Glands

The uptake of iodide represents the first step in thyroid hormone synthesis by thyroid follicular cells and is mediated by the sodium-iodide symporter (NIS). In mammals, expression of NIS is stimulated by TSH and transcription of the NIS gene involves regulation by the thyroid-specific transcription factors Pax8 and Nkx2.1. In this study, we examined the mRNA expression of NIS, Pax8 and Nkx2.1 in the thyroid gland of Xenopus laevis tadpoles by semi-quantitative reverse transcriptase (RT)-PCR. During spontaneous metamorphosis, NIS mRNA expression was low in premetamorphic tadpoles, increased throughout prometamorphosis, and peaked at climax stage 60. Analysis of TSH β-subunit (TSHβ) mRNA in the pituitary of the same tadpoles revealed a close temporal relationship in the expression of the two genes during metamorphosis, suggesting a regulatory role of TSH in the developmental expression of NIS. Treatment of tadpoles with goitrogenic compounds (sodium perchlorate and ethylenethiourea) increased TSHβ mRNA expression (approximately twofold) and caused thyroid gland hyperplasia, confirming that feedback along the pituitary–thyroid axis was operative. Analysis of gene expression in the thyroid gland revealed that goitrogen treatment was correlated with increased expression of NIS mRNA (~20-fold). In the thyroid gland organ culture experiments, bovine TSH (bTSH; 1 mU/ml) strongly induced NIS mRNA expression. This effect was mimicked by co-culture of thyroid glands with pituitaries from stage 58 tadpoles and by agents that increase intracellular cAMP (forskolin, dibutyryl-cAMP). In addition, it could be shown that thyroid glands of X. laevis tadpoles express Pax8 and Nkx2.1 mRNA in a developmentally regulated manner and that ex vivo treatment of thyroid glands with bTSH, forskolin, and cAMP analogs increased the expression of Pax8 and Nkx2.1 mRNA. This is the first report on developmental profiles and hormonal regulation of thyroid gland gene expression in amphibian tadpoles and, together, results reveal a critical role of TSH in the regulation of NIS mRNA expression in the thyroid gland of X. laevis tadpoles.

scholarly journals Propylthiouracil Increases Sodium/Iodide Symporter Gene Expression and Iodide Uptake in Rat Thyroid Cells in the Absence of TSH

Thyroid ◽  
2012 ◽  
Vol 22 (8) ◽  
pp. 844-852 ◽  
Author(s):  
Mariko Sue ◽  
Takeshi Akama ◽  
Akira Kawashima ◽  
Hannah Nakamura ◽  
Takeshi Hara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Rat Thyroid

scholarly journals Enhancement of sodium/iodide symporter expression in thyroid and breast cancer

2006 ◽  
Vol 13 (3) ◽  
pp. 797-826 ◽  
Author(s):  
T Kogai ◽  
K Taki ◽  
G A Brent
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Thyroid Cancer ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Wide Range ◽  
Nis Gene ◽  
Tsh Stimulation

The sodium/iodide symporter (NIS) mediates iodide uptake in the thyroid gland and lactating breast. NIS mRNA and protein expression are detected in most thyroid cancer specimens, although functional iodide uptake is usually reduced resulting in the characteristic finding of a ‘cold’ or non-functioning lesion on a radioiodine image. Iodide uptake after thyroid stimulating hormone (TSH) stimulation, however, is sufficient in most differentiated thyroid cancer to utilize β-emitting radioactive iodide for the treatment of residual and metastatic disease. Elevated serum TSH, achieved by thyroid hormone withdrawal in athyreotic patients or after recombinant human thyrotropin administration, directly stimulates NIS gene expression and/or NIS trafficking to the plasma membrane, increasing radioiodide uptake. Approximately 10–20% differentiated thyroid cancers, however, do not express the NIS gene despite TSH stimulation. These tumors are generally associated with a poor prognosis. Reduced NIS gene expression in thyroid cancer is likely due in part, to impaired trans-activation at the proximal promoter and/or the upstream enhancer. Basal NIS gene expression is detected in about 80% breast cancer specimens, but the fraction with functional iodide transport is relatively low. Lactogenic hormones and various nuclear hormone receptor ligands increase iodide uptake in breast cancer cells in vitro, but TSH has no effect. A wide range of ‘differentiation’ agents have been utilized to stimulate NIS expression in thyroid and breast cancer using in vitro and in vivo models, and a few have been used in clinical studies. Retinoic acid has been used to stimulate NIS expression in both thyroid and breast cancer. There are similarities and differences in NIS gene regulation and expression in thyroid and breast cancer. The various agents used to enhance NIS expression in thyroid and breast cancer will be reviewed with a focus on the mechanism of action. Agents that promote tumor differentiation, or directly stimulate NIS gene expression, may result in iodine concentration in ‘scan-negative’ thyroid cancer and some breast cancer.

scholarly journals Transcriptional Regulation of Human Sodium/Iodide Symporter Gene: A Role for Redox Factor-1

Endocrinology ◽  
2004 ◽  
Vol 145 (3) ◽  
pp. 1290-1293 ◽  
Author(s):  
Cinzia Puppin ◽  
Franco Arturi ◽  
Elisabetta Ferretti ◽  
Diego Russo ◽  
Rosario Sacco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Promoter Activity ◽  
Sodium Iodide ◽  
Independent Effect ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Expression Plasmid ◽  
Thyroid Cells ◽  
Nis Gene

Abstract The transcriptional regulation of the human sodium/iodide symporter (NIS) gene in normal and transformed thyroid cells is a crucial issue in attempting to restore iodide uptake and use radioiodine as a therapeutic treatment of thyroid cancer. Previous investigations have shown that the multifunctional protein apurinic apyrimidinic endonuclease/redox factor 1 (APE/Ref-1) plays an important role in regulation of thyroid-specific gene transcription. In this study, we investigated the effects of APE/Ref-1 on human NIS promoter activity. Cotransfection experiments performed in nonthyroid HeLa cells demonstrated that APE/Ref-1 exerts both PAX8-dependent and PAX8-independent effects. In fact, in the absence of PAX8, overexpression of APE/Ref-1 enhanced NIS promoter activity 2-fold. When the expression plasmid of APE/Ref-1 was transfected together with an expression plasmid for PAX8, a strong cooperative effect was detected with an increase of NIS promoter activity 9-fold over control. The PAX8-independent effect of APE/Ref-1 was specific for the NIS promoter, resulting not present for the promoter of the thyroperoxidase (TPO) gene. It was, at least in part, due to the up-regulation of the transcriptional activity of the ubiquitous factor early growth response-1 (Egr-1). In the thyroid tumor cell lines TPC-1 and B-CPAP, APE/Ref-1 was not effective by itself, and it also failed to increase PAX8 stimulation on NIS promoter activity. These data demonstrate a role for APE/Ref-1 protein in the transcriptional regulation of NIS gene expression by itself and in cooperation with PAX8. However, restoring the PAX8-APE/Ref-1 expression in tumor cells may not be sufficient to obtain adequate levels of NIS gene expression.

Identification of novel sodium iodide symporter (NIS) interactors which modulate iodide uptake

2016 ◽  
Author(s):  
Alice Fletcher ◽  
Vikki Poole ◽  
Bhavika Modasia ◽  
Waraporn Imruetaicharoenchoke ◽  
Rebecca Thompson ◽  
...  
Keyword(s):  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake
Sign in / Sign up

Export Citation Format

Share Document