Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Tokyo 173-8605, Japan.
Department of Pathology, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
Endocr J. 2022 Oct 28;69(10):1217-1225. doi: 10.1507/endocrj.EJ22-0082. Epub 2022 May 28.
Solute carrier family 26 member 7 (SLC26A7), identified as a causative gene for congenital hypothyroidism, was found to be a novel iodide transporter expressed on the apical side of the follicular epithelium of the thyroid. We recently showed that TSH suppressed the expression of SLC26A7 and induces its localization to the plasma membrane, where it functions. We also showed that the ability of TSH to induce thyroid hormone synthesis is completely reversed by an autocrine negative-feedback action of thyroglobulin (Tg) stored in the follicular lumen. In the present study, we investigated the potential effect of follicular Tg on SLC26A7 expression and found that follicular Tg significantly suppressed the promoter activity, mRNA level, and protein level of SLC26A7 in rat thyroid FRTL-5 cells. In addition, follicular Tg inhibited the ability of TSH to induce the membrane localization of SLC26A7. In rat thyroid sections, the expression of SLC26A7 was weaker in follicles with a higher concentration of Tg, as evidenced by immunofluorescence staining. These results indicate that Tg stored in the follicular lumen is a feedback suppressor of the expression and membrane localization of SLC26A7, thereby downregulating the transport of iodide into the follicular lumen.
溶质载体家族 26 成员 7（SLC26A7）被鉴定为先天性甲状腺功能减退症的致病基因，它是一种新型的碘转运体，表达在甲状腺滤泡上皮的顶端。我们最近表明，TSH 抑制 SLC26A7 的表达并诱导其定位到质膜，在质膜上它发挥作用。我们还表明，TSH 诱导甲状腺激素合成的能力完全被滤泡腔内储存的甲状腺球蛋白（Tg）的自分泌负反馈作用所逆转。在本研究中，我们研究了滤泡 Tg 对 SLC26A7 表达的潜在影响，发现滤泡 Tg 显著抑制大鼠甲状腺 FRTL-5 细胞中 SLC26A7 的启动子活性、mRNA 水平和蛋白水平。此外，滤泡 Tg 抑制了 TSH 诱导 SLC26A7 质膜定位的能力。在大鼠甲状腺切片中，免疫荧光染色显示，Tg 浓度较高的滤泡中 SLC26A7 的表达较弱。这些结果表明，滤泡腔内储存的 Tg 是 SLC26A7 表达和质膜定位的反馈抑制剂，从而下调了碘向滤泡腔内的转运。
