Regulation and tissue distribution of the human sodium iodide symporter gene
Regulation and tissue distribution of the human sodium iodide symporter gene
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DOI：
10.1046/j.1365-2265.1998.00570.x
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发表时间：
1998-10-01
影响因子：
3.2
通讯作者：
Weetman, AP
中科院分区：
文献类型：
--
作者：
Ajjan, RA;Kamaruddin, NA;Weetman, AP
目的甲状腺对碘的摄取是由钠碘转运体（NIS）介导的。本研究分析了人NIS mRNA表达和原代培养的甲状腺滤泡细胞（TFC）碘摄取的调控因素。方法体外培养的甲状腺滤泡细胞分别用重组人促甲状腺激素（TSH）和细胞因子处理72 h，用逆转录-聚合酶链反应（RT-PCR）检测NIS基因的表达，用碘-125（I-125）摄取法检测甲状腺滤泡细胞对碘的摄取。结果人TSH可剂量依赖性地增加TFC细胞NIS基因的表达和碘的摄取。使用浓度为0.1 U/l的hTSH，检测到NIS基因表达的轻微增加，而碘摄取没有检测到增加。IL-1 α、TNF α和IFN γ在浓度为10（5）U/l时均抑制TSH诱导的NIS基因表达和碘摄取。在这些实验中，NIS mRNA表达与碘摄取之间存在良好的相关性。使用RT-PCR检测到更高水平的NIS mRNA相比，多结节性甲状腺肿组织样本中的格雷夫斯病（GD）。胃和唾液腺组织也表达NIS mRNA，而乳腺和眼外肌组织中发现低水平，卵巢、食管、结肠、眼外脂肪和皮肤中未检测到NIS mRNA表达。相反，北方印迹分析未能检测到NIS在胃，唾液腺，肠脂肪或无毒的多结节性甲状腺肿组织样品，虽然这是存在于GD甲状腺tissue.CONCLUSION TSH上调钠碘转运体基因表达和碘摄取在初级甲状腺滤泡细胞培养，这种诱导是由细胞因子调制。不同组织样本中存在不同水平的钠碘转运体mRNA，Graves病甲状腺组织中明显存在高表达。
OBJECTIVE lodide 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 72h, Subsequently, NIS gene expression and iodide uptake were analysed using reverse transcription-polymerase chain reaction (RT-PCR) and I-125 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.CONCLUSION 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.