REGULATION AND TISSUE DISTRIBUTION OF THE HUMAN SODIUM-IODIDE SYMPORTER GENE

OBJECTIVE lodide uptake by the thyroid gland is mediated by the sodium iodide symporter (NIS), In the present report, we have analysed the f actors that modulate human NIS mRNA expression and iodide uptake in pr imary thyroid follicular cell (TFC) cultures. In addition, NIS mRNA ti ssue distribution was investigated. METHODS Primary thyroid follicular cell cultures were treated with human recombinant TSH with or without cytokines for 72h, Subsequently, NIS gene expression and iodide uptak e were analysed using reverse transcription-polymerase chain reaction (RT-PCR) and I-125 uptake, respectively. Human tissue samples were inv estigated for NIS gene expression using both RT-PCR and Northern blott ing. RESULTS Human TSH increased both NIS gene expression and iodide u ptake 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 detec ted without a detectable increase in iodide uptake. IL-1 alpha, TNF al pha and IFN gamma at concentrations of 10(5) U/l all inhibited TSH-ind uced NIS gene expression and iodide uptake. In these experiments, ther e was a good correlation between NIS mRNA expression and iodide uptake . Using RT-PCR higher levels of NIS mRNA were detected in Graves' dise ase (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 expressi on was detected in the ovary, oesophagus, colon, extraocular fat or sk in. In contrast, Northern blot analysis failed to detect NIS in stomac h, salivary gland, intestinal fat or non-toxic multi-nodular goitre ti ssue samples, although this was present in GD thyroid tissue. CONCLUSI ON 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 ev ident in Graves' disease thyroid tissue.