Comparison of effects of Iodine-deficiency and perchlorate on thyroid

Perchlorate, which is a ubiquitous and persistent ion, competitively interferes with iodide accumulation in the thyroid, causing iodine deficiency, which may result in reduced thyroid hormone synthesis and secretion. Human studies suggest that perchlorate presents very little risk in healthy individuals; however, the precautionary principle demands that the sensitive populations of iodine deficient adults and mothers require extra consideration. In an attempt to determine if the effects on gene expression were similar, we compared the thyroidal effects of perchlorate (10 mg/kg) treatment for 14 days in drinking water with those caused by 8 weeks of Iodine-deficiency in rats. The thyroids were collected (N=3 each group) and total mRNA was analyzed using the Affymetrix Rat Genome 230 2.0 GeneChip®. Changes in gene expression were compared with appropriate control groups. We compared the 2-fold gene changes due to I-deficiency with changes due to perchlorate treatment. 189 transcripts were changed by the Iodine-deficient diet and 722 transcripts were changed by the perchlorate treatment. 34% of the transcripts changed by the I-deficient diet were also changed by perchlorate and generally in the same direction. three specific transporter genes, AQP1, NIS, & SLC22A3 were changed by both treatments, indicating that the membrane specific changes were similar. Iodine-deficiency primarily caused changes in retinol and calcium signaling pathways and perchlorate primarily caused changes related to the accumulation of extracellular matrix proteins. This study provides evidence that perchlorate, at least at this dose level, changes more genes and changes different genes compared to iodine deficiency.高氯酸盐(Perchlorate)是一种普遍存在且性质稳定的离子，可竞争性干扰甲状腺内碘离子的蓄积，引发碘缺乏，进而可能导致甲状腺激素合成与分泌减少。人体研究表明，高氯酸盐对健康个体几乎无风险；但基于预防原则，碘缺乏成人与孕产妇这类敏感人群需予以额外关注。 为探究二者对基因表达的影响是否相似，本研究以大鼠为模型，对比了饮水给予10 mg/kg高氯酸盐、连续14天，与8周碘缺乏对甲状腺产生的影响。采集各组甲状腺组织（每组n=3），采用Affymetrix大鼠基因组230 2.0基因芯片®（Affymetrix Rat Genome 230 2.0 GeneChip®）分析总mRNA表达水平。以相应对照组为参照，分析基因表达变化情况，并对比了碘缺乏与高氯酸盐处理引发的2倍差异基因表达变化。 碘缺乏日粮可使189个转录本发生表达变化，高氯酸盐处理则可改变722个转录本的表达；其中碘缺乏日粮引发变化的转录本中有34%同时受高氯酸盐调控，且表达变化方向基本一致。两种处理均改变了3个特定转运蛋白基因（AQP1、NIS与SLC22A3）的表达，提示细胞膜相关特异性变化具有相似性。 碘缺乏主要影响视黄醇与钙信号通路相关基因的表达，而高氯酸盐则主要调控细胞外基质蛋白蓄积相关通路的基因表达。本研究证实，至少在该给药剂量下，相较于碘缺乏，高氯酸盐可调控更多基因的表达，且调控的基因种类存在差异。