Propylthiouracil Increases Sodium/Iodide Symporter Gene Expression and Iodide Uptake in Rat Thyroid Cells in the Absence of TSH
Propylthiouracil Increases Sodium/Iodide Symporter Gene Expression and Iodide Uptake in Rat Thyroid Cells in the Absence of TSH
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DOI：
10.1089/thy.2011.0290
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发表时间：
2012-08-01
期刊：
影响因子：
6.6
通讯作者：
Suzuki, Koichi
中科院分区：
文献类型：
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作者：
Sue, Mariko;Akama, Takeshi;Suzuki, Koichi
背景：丙基硫脲嘧啶（PTU）和甲巯咪唑（MMI）是目前广泛用于治疗Graves病的药物。虽然两者主要通过阻断甲状腺过氧化物酶活性发挥抗甲状腺作用，但它们的分子结构和其他作用是不同的。我们假设PTU和MMI可能对甲状腺特异性基因表达和功能有不同的影响。方法：采用DNA芯片、逆转录酶(RT)-聚合酶链式反应（PCR）、实时荧光定量PCR、Western blot、免疫组织化学和放射性碘摄取等方法检测PTU和MMI对大鼠甲状腺FRTL-5细胞甲状腺特异性基因表达和功能的影响。结果：DNA微阵列分析显示，PTU治疗后，钠/碘化物同调体（NIS）基因表达显著增加，而MMI没有影响。RT-PCR和real-time PCR分析显示，ptu诱导的NIS mRNA水平与促甲状腺激素（TSH）诱导的水平相当。PTU增加了大鼠NIS启动子5′-1880-bp和5′-1052-bp的活性。虽然PTU处理也增加了NIS蛋白水平，但诱导蛋白的大小比TSH诱导的小，并且蛋白质主要定位于细胞质而不是质膜。PTU刺激可增加FRTL-5细胞中125 I的积累，但这种作用弱于TSH。结论：我们发现PTU在缺乏TSH的情况下诱导大鼠甲状腺FRTL-5细胞NIS表达和碘化物摄取。虽然PTU和MMI具有相似的抗甲状腺活性，但它们对其他甲状腺功能的影响似乎大不相同，这可能影响它们的治疗效果。
Background: Propylthiouracil (PTU) and methimazole (MMI) are drugs that are widely used to treat Graves' disease. Although both exert an antithyroid effect primarily by blocking thyroid peroxidase activity, their molecular structure and other actions are different. We hypothesized that PTU and MMI may have differential effects on thyroid-specific gene expression and function.Methods: The effects of PTU and MMI on thyroid-specific gene expression and function were examined in rat thyroid FRTL-5 cells using DNA microarray, reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blot, immunohistochemistry, and radioiodine uptake studies.Results: DNA microarray analysis showed a marked increase in sodium/iodide symporter (NIS) gene expression after PTU treatment, whereas MMI had no effect. RT-PCR and real-time PCR analysis revealed that PTU-induced NIS mRNA levels were comparable to those elicited by thyroid-stimulating hormone (TSH). PTU increased 5'-1880-bp and 5'-1052-bp activity of the rat NIS promoter. While PTU treatment also increased NIS protein levels, the size of the induced protein was smaller than that induced by TSH, and the protein localized predominantly in the cytoplasm rather than the plasma membrane. Accumulation of 125 I in FRTL-5 cells was increased by PTU stimulation, but this effect was weaker than that produced by TSH.Conclusions: We found that PTU induces NIS expression and iodide uptake in rat thyroid FRTL-5 cells in the absence of TSH. Although PTU and MMI share similar antithyroid activity, their effects on other thyroid functions appear to be quite different, which could affect their therapeutic effectiveness.