scholarly journals Induction of follicle formation in long-term cultured normal human thyroid cells treated with thyrotropin stimulates iodide uptake but not sodium/iodide symporter messenger RNA and protein expression

2000 ◽  
Vol 167 (1) ◽  
pp. 125-135 ◽  
Author(s):  
T Kogai ◽  
F Curcio ◽  
S Hyman ◽  
EM Cornford ◽  
GA Brent ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Sodium Iodide ◽  
Human Thyroid ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Protein Levels ◽  
Normal Human ◽  
Tsh Stimulation ◽  
Stimulation Of

Iodide uptake by the sodium/iodide symporter (NIS) in thyrocytes is essential for thyroid hormone production. Reduced NIS activity has been reported in thyroid diseases, including thyroid cancer and congenital hypothyroidism. The study of iodide uptake in thyrocytes has been limited by the availability of appropriate in vitro models. A new culture technique was recently developed that allows normal human thyroid primary culture cells to grow as monolayer cells and express differentiated functions for more than 3 months. We used this technique to study the effect of follicle formation and TSH on iodide uptake in these cells. Iodide uptake by the cells grown in monolayer was very low. Follicle formation was induced from monolayer cells, and electron micrographs demonstrated cell polarity in the follicles. No significant increase in iodide uptake was observed after TSH treatment of cells in monolayer or when follicle formation was induced without TSH. TSH stimulation of follicles, however, significantly increased iodide uptake ( approximately 4. 4-fold; P<0.001). Compared with iodide uptake in monolayers, the combination of follicle formation and TSH treatment stimulated iodide uptake synergistically to 12.0-fold (P<0.001). NIS messenger RNA (mRNA) and protein levels were almost the same in both monolayer cells and follicles. TSH treatment of monolayers and follicles produced significant (P<0.05) stimulation of mRNA ( approximately 4. 8- and approximately 4.3-fold respectively) and protein ( approximately 6.8- and 4.9-fold respectively). TSH stimulated NIS protein levels in both monolayer and follicles, however, stimulation of functional iodide uptake was only seen with TSH stimulation of follicles. The function of NIS may involve post-transcriptional events, such as intracellular sorting, membrane localization of NIS or another NIS regulatory factor. Polarized functions, such as iodide efflux into follicular lumina, may also contribute to the increased iodide concentration after follicle formation.

Reestablishment of In Vitro and In Vivo Iodide Uptake by Transfection of the Human Sodium Iodide Symporter (hNIS) in a hNIS Defective Human Thyroid Carcinoma Cell Line

Thyroid ◽  
2000 ◽  
Vol 10 (11) ◽  
pp. 939-943 ◽  
Author(s):  
Jan W.A. Smit ◽  
Janny P. Schröder-van der Elst ◽  
Marcel Karperien ◽  
Ivo Que ◽  
Gabri van der Pluijm ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Cell Line ◽  
Sodium Iodide ◽  
Carcinoma Cell ◽  
Human Thyroid ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Thyroid Carcinoma Cell

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

IN-VITRO STUDIES OF NORMAL HUMAN THYROID CELLS: RESPONSES TO THYROTROPHIN AND DIBUTYRYL CYCLIC AMP

1977 ◽  
Vol 72 (1) ◽  
pp. 87-96 ◽  
Author(s):  
S. P. BIDEY ◽  
P. MARSDEN ◽  
J. ANDERSON ◽  
C. G. McKERRON ◽  
H. BERRY
Keyword(s):  
Cyclic Amp ◽  
Thyroid Tissue ◽  
Three Dimensional ◽  
Human Thyroid ◽  
Dibutyryl Cyclic Amp ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Normal Human

SUMMARY Follicular cells isolated from normal human thyroid tissue have been cultured for up to 140 h with bovine thyrotrophin (TSH) or dibutyryl cyclic AMP (DBcAMP). Both compounds induced marked reorganization of the cells into three-dimensional follicular structures, whilst non-supplemented cells assumed a monolayer form. Cultures treated initially with TSH or DBcAMP showed a greater iodide uptake capacity, in comparison with unsupplemented cultures, in which iodide uptake was markedly diminished after 24 h. The release of tri-iodothyronine (T3) and thyroxine (T4) into the medium was determined by radioimmunoassay. Both TSH- and DBcAMP-treated cells showed a significant increase in iodothyronine output compared with unsupplemented control cells. In contrast to the 'classical' TSH-induced depression of the T4:T3 ratio in vivo, an increase in the ratio was observed for both TSH- and DBcAMP-supplemented cells in vitro. The ratio was also significantly greater after TSH than after DBcAMP, and possible implications of this finding are discussed.

scholarly journals Forskolin, 8-Br-3′,5′-Cyclic Adenosine 5′-Monophosphate, and Catalytic Protein Kinase A Expression in the Nucleus Increase Radioiodide Uptake and Sodium/Iodide Symporter Protein Levels in RET/PTC1-Expressing Cells

2004 ◽  
Vol 89 (12) ◽  
pp. 6168-6172 ◽  
Author(s):  
Anjli Venkateswaran ◽  
Derek K. Marsee ◽  
Steven H. Green ◽  
Sissy M. Jhiang
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Thyroid Cells ◽  
Protein Levels ◽  
And Function ◽  
Kinase A

Abstract RET/PTC1, a thyroid-specific oncogene, has been reported to down-regulate sodium/iodide symporter (NIS) expression and function in vitro and in vivo. Recently, RET/PTC1 has been shown to interfere with TSH signaling at multiple levels in thyroid cells. The objective of this study was to investigate whether RET/PTC1-mediated NIS reduction can be rescued by activating cAMP-protein kinase A (PKA) pathways. We showed that both forskolin and 8-Br-cAMP increase radioiodide uptake and NIS protein in RET/PTC1-expressing cells to the same extent as the parental PC Cl 3 cells. We found that RET/PTC1 decreases nuclear localization of catalytic PKA, and forskolin treatment was able to counteract this RET/PTC1 effect. Furthermore, transient expression of catalytic PKA in the nucleus increased radioiodide uptake and NIS protein in RET/PTC1-expressing cells. Taken together, these studies suggest that RET/PTC1 down-regulates NIS expression by interrupting TSH/cAMP signaling, and this RET/PTC1 effect can be reversed by activating cAMP-PKA pathways.

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 MEK signaling modulates sodium iodide symporter at multiple levels and in a paradoxical manner

2007 ◽  
Vol 14 (2) ◽  
pp. 421-432 ◽  
Author(s):  
Douangsone D Vadysirisack ◽  
Anjli Venkateswaran ◽  
Zhaoxia Zhang ◽  
Sissy M Jhiang
Keyword(s):  
Cell Surface ◽  
Atpase Activity ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Thyroid Cancers ◽  
Protein Levels ◽  
Radioiodine Ablation

The Na+/I− symporter (NIS)-mediated iodide uptake is the basis for targeted radioiodine ablation of thyroid cancers. However, NIS-mediated radioiodide uptake (RAIU) activity is often reduced in thyroid cancers. As mitogen activated protein kinase (MAPK) signaling pathway is activated in about 70% of papillary thyroid carcinoma, we investigated whether MEK (MAPK kinase) inhibition will restore NIS protein levels and NIS-mediated RAIU activity in RET/PTC oncogene-transformed thyroid cells. We found that MEK inhibitor PD98059 increased NIS protein levels within 30 min of treatment. However, the increase of NIS protein level was not accompanied with an increase in NIS-mediated RAIU activity, particularly at early time points of PD98059 treatment. PD98059 also decreased RAIU activity mediated by exogenous NIS in non-thyroid cells. The transient decrease of RAIU activity by PD98059 in thyroid cells was not due to decreased NIS cell surface level, decreased NIS binding affinity for I− , or increased iodide efflux. While PD98059 moderately decreased Na+/K+-ATPase activity, ouabain titration indicates that the extent of decrease in Na+/K+-ATPase activity is much greater than the extent of decrease in RAIU activity. Additionally, a decrease of Na+/K+-ATPase activity was not accompanied with a decrease of biotin uptake activity mediated by Na+-dependent multivitamin transporter. Since PD98059 reduced Vmax− I− without decreasing NIS cell surface levels, it is most likely that PD98059 decreases the turnover rate of iodide transport with an yet to be identified mechanism.

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
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