TSH Regulates Pendrin Membrane Abundance and Enhances Iodide Efflux in Thyroid Cells
TSH Regulates Pendrin Membrane Abundance and Enhances Iodide Efflux in Thyroid Cells
复制标题
DOI：
10.1210/en.2011-1548
复制
发表时间：
2012-01-01
期刊：
影响因子：
4.8
通讯作者：
Kopp, Peter
中科院分区：
文献类型：
--
作者：
Pesce, Liuska;Bizhanova, Aigerim;Kopp, Peter
甲状腺激素是正常发育和新陈代谢所必需的。它们的合成需要将碘离子转运到甲状腺滤泡中。碘化物进入卵泡腔的根尖外排机制尚不清楚。在Pendred综合征（先天性耳聋、甲状腺肿和碘化物组织缺陷）患者中发现的SLC26A4基因突变表明，编码蛋白penddrin可能是一种顶端碘化物转运蛋白。我们确定TSH是否调节质膜上的penddrin丰度，以及这是否影响碘化物的外排。免疫印迹和免疫荧光实验结果显示，TSH和forskolin通过蛋白激酶A途径迅速增加PCCL-3大鼠甲状腺细胞质膜上pendrin的丰度。penddrin膜丰度的增加与细胞内碘含量的减少相关，这是通过测量细胞内（125）碘含量来确定的，并且可以通过特异性阻断penddrin来抑制。消除假定的蛋白激酶A磷酸化位点T717A导致对福斯克林的反应减少了对膜的易位。这些结果表明，penddrin在TSH的作用下易位到细胞膜上，并可能在根尖碘化物运输和甲状腺激素合成中发挥生理作用。（内分泌学153:512-521,2012）
Thyroid hormones are essential for normal development and metabolism. Their synthesis requires transport of iodide into thyroid follicles. The mechanisms involving the apical efflux of iodide into the follicular lumen are poorly elucidated. The discovery of mutations in the SLC26A4 gene in patients with Pendred syndrome (congenital deafness, goiter, and defective iodide organification) suggested a possible role for the encoded protein, pendrin, as an apical iodide transporter. We determined whether TSH regulates pendrin abundance at the plasma membrane and whether this influences iodide efflux. Results of immunoblot and immunofluorescence experiments reveal that TSH and forskolin rapidly increase pendrin abundance at the plasma membrane through the protein kinase A pathway in PCCL-3 rat thyroid cells. The increase in pendrin membrane abundance correlates with a decrease in intracellular iodide as determined by measuring intracellular (125)iodide and can be inhibited by specific blocking of pendrin. Elimination of the putative protein kinase A phosphorylation site T717A results in a diminished translocation to the membrane in response to forskolin. These results demonstrate that pendrin translocates to the membrane in response to TSH and suggest that it may have a physiological role in apical iodide transport and thyroid hormone synthesis. (Endocrinology 153: 512-521, 2012)