Pendrin, the protein encoded by the Pendred syndrome gene (PDS), is an apical porter of iodide in the thyroid and is regulated by thyroglobulin in FRTL-5 cells
Pendrin, the protein encoded by the Pendred syndrome gene (PDS), is an apical porter of iodide in the thyroid and is regulated by thyroglobulin in FRTL-5 cells
复制标题
DOI：
10.1210/en.141.2.839
复制
发表时间：
2000-02-01
期刊：
影响因子：
4.8
通讯作者：
Green, ED
中科院分区：
文献类型：
--
作者：
Royaux, IE;Suzuki, K;Green, ED
Pendred综合征是一种常染色体隐性遗传疾病，以先天性耳聋和甲状腺肿大为特征。甲状腺疾病通常在青春期左右发展，并与轻度有机化缺陷有关，其特征在于高氯酸盐刺激时碘的不适当排放（阳性高氯酸盐排放试验）。在Pendred综合征中突变的基因（PDS）在甲状腺中表达，编码一种780个氨基酸的蛋白质（pendrin），最近已被证明是碘/氯转运蛋白。我们试图建立pendrin在甲状腺中的位置，并检查控制其合成的调控网络。使用肽特异性抗体进行免疫定位研究，pendrin在甲状腺滤泡内的有限细胞亚群中检测到，仅在滤泡上皮的顶膜处。有趣的是，在Graves病患者的甲状腺组织中发现了显著更大量的pendrin。使用培养的大鼠甲状腺细胞系（FRTL-5），PDS的表达被发现显着诱导低浓度的甲状腺球蛋白（TG），但不是由TSH，碘化钠，或胰岛素。这与TG的既定作用不同，TG更典型地是甲状腺特异性基因表达的有效抑制剂。总之，这些结果表明，pendrin是碘在甲状腺中的顶端转运蛋白，并且顶端和基底碘转运蛋白的表达和功能由滤泡TG协调调节。
Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and thyroid goiter. The thyroid disease typically develops around puberty and is associated with a mild organification defect, characterized by an inappropriate discharge of iodide upon perchlorate stimulation (a positive perchlorate discharge test). The gene (PDS) mutated in Pendred syndrome is expressed in thyroid and encodes a 780-amino acid protein (pendrin) that has recently been shown to function as an iodide/chloride transporter. We sought to establish the location of pendrin in the thyroid and to examine the regulatory network controlling its synthesis. Using peptide-specific antibodies for immunolocalization studies, pendrin was detected in a limited subset of cells within the thyroid follicles, exclusively at the apical membrane of the follicular epithelium. Interestingly, significantly greater amounts of pendrin were encountered in thyroid tissue from patients with Graves' disease. Using a cultured rat thyroid cell line (FRTL-5), PDS expression was found to be significantly induced by low concentrations of thyroglobulin (TG), but not by TSH, sodium iodide, or insulin. This is different from the established effect of TG, more typically a potent suppressor of thyroid-specific gene expression. Together, these results suggest that pendrin is an apical porter of iodide in the thyroid and that the expression and function of both the apical and basal iodide porters are coordinately regulated by follicular TG.