Follicular thyroglobulin suppresses iodide uptake by suppressing expression of the sodium/iodide symporter gene
Follicular thyroglobulin suppresses iodide uptake by suppressing expression of the sodium/iodide symporter gene
复制标题
DOI：
10.1210/en.140.11.5422
复制
发表时间：
1999-11-01
期刊：
影响因子：
4.8
通讯作者：
Kohn, LD
中科院分区：
文献类型：
--
作者：
Suzuki, K;Mori, A;Kohn, LD
甲状腺细胞的主要功能是吸收和浓缩碘化物。这是甲状腺激素合成所必需的，并由碘化钠同向转运体 (NIS) 完成，其表达和活性受 TSH 上调。最近，我们报道滤泡甲状腺球蛋白（TG）是甲状腺特异性基因表达的有效抑制剂，可以克服 TSH 增加的基因表达。我们认为这可能是一种负反馈、自动调节机制，可以抵消 TSH 对卵泡功能的刺激。在本报告中，我们通过协调评估 TG 对 NIS 基因表达和碘化物转运的调节来支持这一假设。我们发现，TG 的生理浓度类似地显着抑制 TSH 增加的 NIS 启动子活性、NIS 蛋白、NIS 依赖性碘化物摄取以及 RNA 水平。我们在体内证明，面向滤泡腔的甲状腺细胞顶膜处的 TG 积累与放射性碘化物吸收的减少有关。因此，TG 很可能在体内抑制 NIS 依赖性碘化物吸收和 NIS 基因表达，就像在体外的情况一样。 NIS 和血管内皮生长因子/血管通透因子的 RNA 水平据报道受 TSH 调节，可能与 TSH 增加的碘化物摄取有关，作为浓度和时间的函数，通过滤泡 TG 协调降低。此外，从培养基中去除滤泡 TG，但不去除 TSH，可以协调地将 NIS 和血管内皮生长因子/血管通透性因子 RNA 水平恢复到 TSH 刺激状态。因此，卵泡腔中积累的 TG 似乎是关键 TSH 增加的卵泡功能、碘吸收和血管通透性的负反馈调节剂。
A major function of the thyrocyte is to take up and concentrate iodide. This is needed for thyroid hormone synthesis and is accomplished by the sodium iodide symporter (NIS), whose expression and activity are up-regulated by TSH. Recently, we reported that follicular thyroglobulin (TG) is a potent suppressor of thyroid-specific gene expression and can overcome TSH-increased gene expression. We suggested this might be a negative feedback, autoregulatory mechanism that counterbalanced TSH stimulation of follicular function. In this report, we support this hypothesis by coordinately evaluating TG regulation of NIS gene expression and iodide transport. We show that physiological concentrations of TG similarly and significantly suppress TSH-increased NIS promoter activity, NIS protein, and NIS-dependent iodide uptake as well as RNA levels. We show, in vivo, that TG accumulation at the apical membrane of a thyrocyte facing the follicular lumen is associated with decreased uptake of radioiodide. It is likely, therefore, that TG suppresses NIS-dependent iodide uptake and NIS gene expression in vivo, as is the case in vitro. RNA levels of NIS and vascular endothelial growth factor/vascular permeability factor, which has been reported to be TSH regulated and possibly associated with TSH-increased iodide uptake, are coordinately decreased by follicular TG as a function of concentration and time. Also, removal of follicular TG from the medium, but not TSH, coordinately returns NIS and vascular endothelial growth factor/vascular permeability factor RNA levels to their TSH-stimulated state. TG accumulated in the follicular lumen appears, therefore, to be a negative feedback regulator of critical TSH-increased follicular functions, iodide uptake, and vascular permeability.