Department of Internal Medicine, Division of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
Genomics. 2011 Feb;97(2):94-100. doi: 10.1016/j.ygeno.2010.10.007. Epub 2010 Oct 28.
Thyroid autonomy is a frequent cause of thyrotoxicosis in regions with iodine deficiency. Epidemiological data suggest that iodide may influence the course of pre-existing thyroid autonomy. Making use of FRTL-5 cells stably expressing a constitutively activating TSH receptor mutation as an in vitro model of thyroid autonomy, we investigated the impact of iodide on proliferation, function and changes in global gene expression. We demonstrate that iodine inhibits growth in TSHR WT and L629F mutant FRTL-5 cells and downregulates e.g. protocadherin cluster (Pcdha1-13) and thyroid responsive element (Thrsp). In addition functional genes e.g. iodotyrosine deiodinase (iyd) and oncogen junB are upregulated, while sodium-iodide-symporter (Nis) and thyroid peroxidase (Tpo) are downregulated by iodide. Iodide tunes down the biological activity of autonomous thyrocytes and may thus be of therapeutic benefit not only to prevent the occurrence of somatic TSHR mutations, causing thyroid autonomy, but also to slow down the development of clinically relevant disease.
甲状腺自主功能是碘缺乏地区甲状腺功能亢进症的常见病因。流行病学数据表明，碘可能会影响已存在的甲状腺自主功能的病程。本研究利用稳定表达组成性激活 TSH 受体突变的 FRTL-5 细胞作为甲状腺自主功能的体外模型，研究了碘对增殖、功能和全基因组表达变化的影响。结果表明，碘抑制 TSHR WT 和 L629F 突变 FRTL-5 细胞的生长，并下调原钙黏蛋白簇（Pcdha1-13）和甲状腺反应元件（Thrsp）等基因。此外，碘还上调功能性基因，如碘酪氨酸脱碘酶（iyd）和原癌基因 junB，而下调钠碘转运体（Nis）和甲状腺过氧化物酶（Tpo）。碘可调节自主甲状腺细胞的生物学活性，因此不仅对预防引起甲状腺自主功能的体细胞 TSHR 突变的发生具有治疗益处，而且对减缓临床相关疾病的发展也具有治疗益处。
