Regulation and tissue distribution of the human sodium iodide symporter gene.
OBJECTIVE
Iodide uptake by the thyroid gland is mediated by the sodium iodide symporter (NIS). In the present report, we have analysed the factors that modulate human NIS mRNA expression and iodide uptake in primary thyroid follicular cell (TFC) cultures. In addition, NIS mRNA tissue distribution was investigated.


METHODS
Primary thyroid follicular cell cultures were treated with human recombinant TSH with or without cytokines for 72 h. Subsequently, NIS gene expression and iodide uptake were analysed using reverse transcription-polymerase chain reaction (RT-PCR) and 125I uptake, respectively. Human tissue samples were investigated for NIS gene expression using both RT-PCR and Northern blotting.


RESULTS
Human TSH increased both NIS gene expression and iodide uptake in TFC cultures in a dose-dependent manner. Using concentrations of 0.1 U/l of hTSH, a minor increase in NIS gene expression was detected without a detectable increase in iodide uptake. IL-1 alpha, TNF alpha and IFN gamma at concentrations of 10(5) U/l all inhibited TSH-induced NIS gene expression and iodide uptake. In these experiments, there was a good correlation between NIS mRNA expression and iodide uptake. Using RT-PCR higher levels of NIS mRNA were detected in Graves' disease (GD) compared to multi-nodular goitre tissue samples. Stomach and salivary gland tissue also expressed NIS mRNA, whereas low levels were found in the mammary gland and extraocular muscle tissue. No expression was detected in the ovary, oesophagus, colon, extraocular fat or skin. In contrast, Northern blot analysis failed to detect NIS in stomach, salivary gland, intestinal fat or non-toxic multi-nodular goitre tissue samples, although this was present in GD thyroid tissue.


CONCLUSIONS
TSH upregulates sodium iodide symporter gene expression and iodide uptake in primary thyroid follicular cell cultures, and this induction is modulated by cytokines. Variable levels of sodium iodide symporter mRNA are present in different tissue samples, with high expression evident in Graves' disease thyroid tissue.
Ajjan
R A
RA
Department of Medicine, University of Sheffield, UK.
Kamaruddin
N A
NA
Crisp
M
M
Watson
P F
PF
Ludgate
M
M
Weetman
A P
AP
D000199:Actins / Q000032:analysis; D015152:Blotting, Northern; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007454:Iodides / Q000378:metabolism; D007457:Iodine Radioisotopes; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000099209:Sodium-Iodide Symporters
D000199:Actins; D002352:Carrier Proteins; D007371:Interferon-gamma; D007375:Interleukin-1; D007454:Iodides; D007457:Iodine Radioisotopes; D008565:Membrane Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D027981:Symporters; D013972:Thyrotropin; D014409:Tumor Necrosis Factor-alpha; D000099209:Sodium-Iodide Symporters