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

Arturi, Franco; Presta, Ivan; Scarpelli, Daniela; Bidart, Jean Michel; Schlumberger, Martin; Russo, Diego

doi:10.1530/eje.0.1470655

Cited by 19 publications

(13 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…hCG upregulates NIS expression in thyroid cells and placental cell lines (4,5,31,33). To examine whether the decrease of NIS expression in low O 2 levels could be contributed to by low hCG levels, we examined hCG mRNA expression and protein secretion in the same samples used for NIS.…”

Section: Discussionmentioning

confidence: 99%

“…Pendrin is an anion exchanger (37,50,53,55) and is activated by high concentrations of intracellular iodide (63). The pituitary glycoprotein TSH upregulates NIS expression and iodide uptake (5,29), whereas iodide has the opposite effect (15). In placenta, materno-fetal transfer of iodide involves iodide uptake through the apical trophoblast cell membrane and efflux through the basal cell membrane.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Effect of oxygen concentrations on sodium iodide symporter expression and iodide uptake and hCG expression in human choriocarcinoma BeWo cells

Landers

Patel

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Normal human fetal development requires an adequate supply of thyroid hormone from conception. Until about 16 wk gestation this is supplied entirely by placental transfer of maternal hormone. Subsequently, the fetal thyroid synthesizes thyroid hormones, requiring a supply of maternal iodide. Trophoblast iodide transfer is mediated by the apical sodium iodide symporter (NIS). Placental oxygen levels are low in early pregnancy (∼1%), rising with placental vascularisation to a plateau of ∼8% at about 16 wk. Although the impact of these changing oxygen levels on placental implantation is well recognized, effects on trophoblast materno-fetal exchange are less understood. We investigated expression of the NIS regulator hCG, NIS mRNA expression, and I125 uptake in choriocarcinoma BeWo cells (a model of the trophoblast) cultured in 1 and 8% oxygen and in room air (21% oxygen). Expression of NIS and hCG mRNA and protein was low at 1% oxygen but rose significantly at 8 and at 21%. This was reflected in significant increases in I125 uptake. Desferrioxamine, an iron chelator and hypoxia mimic, decreased NIS and hCG expression and I125 uptake in BeWo cells. NIS expression and I125 uptake in cells grown at 1% oxygen were not increased by addition of hCG (2,500 IU/l). We infer that placental NIS mRNA and protein expression are regulated by oxygen, rising with vascularization of the placenta in the late first trimester, a time when fetal iodide requirements are increasing.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effect of oxygen concentrations on sodium iodide symporter expression and iodide uptake and hCG expression in human choriocarcinoma BeWo cells

Landers

Patel

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…TSH stimulates the NIS promoter and NIS upstream enhancer (NUE; , Ohmori et al 1998, Ohno et al 1999, Taki et al 2002, increases the half-life of the NIS protein, and stimulates the trafficking of the NIS to the plasma membrane (Riedel et al 2001). Direct stimulation of the TSH receptor in Graves' disease by antibody (Saito et al 1997, Caillou et al 1998, Castro et al 1999, Lazar et al 1999, constitutive activating mutations of the TSH receptor in a hyperfunctioning thyroid adenoma (Mian et al 2001), or the weak agonist human chorionic gonadotropin (hCG; Hershman 1999, Arturi et al 2002, activate the cAMP pathway and result in marked NIS expression. In contrast, the expression of AIT is not increased in hyperfunctioning thyroid adenomas or Graves' disease (Lacroix et al 2004, Porra et al 2005.…”

Section: Tsh Regulation Of Nis and Other Iodide Transporters In Normamentioning

confidence: 99%

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

Kogai¹,

Taki²,

Brent³

2006

Endocr Relat Cancer

168

150

View full text Add to dashboard Cite

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 b-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.

show abstract

“…In the present study, we found that NIS gene expression is downregulated by ATDs. Genetic factors, such as the proximal promoters including thyroid transcription factor 1 (TTF1), NIS TSH-responsive factor 1 (NTF1) or NIS upstream enhancers, iodine, cytokines and anti-NIS antibody, are known to regulate NIS gene expression [21][22][23]. These factors may also have influenced NIS expression in the present study.…”

Section: Discussionmentioning

confidence: 72%

NIS mRNA Expression Level in Resected Thyroid Tissue as a Marker of Postoperative Hypothyroidism after Subtotal Thyroidectomy in Patients with Graves' Disease

et al. 2008

View full text Add to dashboard Cite

Abstract. Subtotal thyroidectomy for Graves' disease sometimes leads to hypothyroidism or relapse during long-term follow-up in a significant proportion of patients. Factors predictive of postoperative hypothyroidism after subtotal thyroidectomy are not known. The objective of this study was to determine the relation between clinical features and expression of transcripts associated with thyroid hormone synthesis in resected thyroid tissues of patients with Graves' disease. Thyroid tissues were obtained from 65 patients with Graves' disease who underwent subtotal thyroidectomy. Expression of mRNAs from thyroglobulin (Tg), TSH receptor (TSHR), thyroid peroxidase (TPO), sodium/iodide symporter (NIS), and the Pendred's syndrome (PDS) genes were analyzed by quantitative reverse transcriptionpolymerase chain reaction. Uni-and multivariate analyses were performed to identify for postoperative hypothyroidism. We detected significant correlations between the NIS mRNA level and levels of free T 3 (fT 3 ) and free T 4 (fT 4 ) and between the Tg mRNA level and goiter weight before initial drug treatment. Mean levels of expression of all five mRNAs were significantly higher in patients who did not require L-thyroxine replacement therapy than in those who required replacement therapy at 6 months after surgery. In patients who did not require replacement therapy, a significant correlation was found between NIS mRNA expression and fT 4 levels. Univariate analysis revealed that decreased NIS mRNA expression (NIS/PGK<1.69) and low TBII levels before initial treatment were significant of postoperative hypothyroidism. Multivariate analysis showed decreased expression of NIS mRNA (NIS/PGK<1.69) to be an independent risk factor for L-thyroxine replacement after surgery (risk ratio, 3.26, confidence interval, 1.36-9.08, p<0.01). NIS expression reflects the level of thyroid hormone synthesis in Graves' disease patients. Evaluation of NIS mRNA expression in thyroid tissues may help determine prognoses of Graves' disease patients, and therefore an appropriate treatment can be determined for each patient.

show abstract

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

Cited by 19 publications

References 40 publications

Effect of oxygen concentrations on sodium iodide symporter expression and iodide uptake and hCG expression in human choriocarcinoma BeWo cells

Effect of oxygen concentrations on sodium iodide symporter expression and iodide uptake and hCG expression in human choriocarcinoma BeWo cells

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

NIS mRNA Expression Level in Resected Thyroid Tissue as a Marker of Postoperative Hypothyroidism after Subtotal Thyroidectomy in Patients with Graves' Disease

Contact Info

Product

Resources

About