Bizhanova Aigerim, Kopp Peter
Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Endocrinology. 2009 Mar;150(3):1084-90. doi: 10.1210/en.2008-1437. Epub 2009 Feb 5.
Thyroid hormones are essential for normal development and metabolism. Thyroid hormone biosynthesis requires iodide uptake into the thyrocytes and efflux into the follicular lumen, where it is organified on selected tyrosyls of thyroglobulin. Uptake of iodide into the thyrocytes is mediated by an intrinsic membrane glycoprotein, the sodium-iodide symporter (NIS), which actively cotransports two sodium cations per each iodide anion. NIS-mediated transport of iodide is driven by the electrochemical sodium gradient generated by the Na(+)/K(+)-ATPase. NIS is expressed in the thyroid, the salivary glands, gastric mucosa, and the lactating mammary gland. TSH and iodide regulate iodide accumulation by modulating NIS activity via transcriptional and posttranscriptional mechanisms. Biallelic mutations in the NIS gene lead to a congenital iodide transport defect, an autosomal recessive condition characterized by hypothyroidism, goiter, low thyroid iodide uptake, and a low saliva/plasma iodide ratio. Pendrin is an anion transporter that is predominantly expressed in the inner ear, the thyroid, and the kidney. Biallelic mutations in the SLC26A4 gene lead to Pendred syndrome, an autosomal recessive disorder characterized by sensorineural deafness, goiter, and impaired iodide organification. In thyroid follicular cells, pendrin is expressed at the apical membrane. Functional in vitro data and the impaired iodide organification observed in patients with Pendred syndrome support a role of pendrin as an apical iodide transporter.
甲状腺激素对正常发育和新陈代谢至关重要。甲状腺激素的生物合成需要碘化物摄取进入甲状腺细胞并流入滤泡腔，在那里它在甲状腺球蛋白的特定酪氨酸上进行有机化。碘化物进入甲状腺细胞是由一种内在膜糖蛋白——钠碘同向转运体（NIS）介导的，它每转运一个碘离子就主动协同转运两个钠离子。NIS介导的碘化物转运由Na(+)/K(+)-ATP酶产生的电化学钠梯度驱动。NIS在甲状腺、唾液腺、胃黏膜和泌乳乳腺中表达。促甲状腺激素（TSH）和碘化物通过转录和转录后机制调节NIS活性来调节碘化物的积累。NIS基因的双等位基因突变导致先天性碘转运缺陷，这是一种常染色体隐性疾病，其特征为甲状腺功能减退、甲状腺肿、甲状腺碘摄取低以及唾液/血浆碘化物比值低。pendrin是一种阴离子转运体，主要在内耳、甲状腺和肾脏中表达。SLC26A4基因的双等位基因突变导致 Pendred综合征，这是一种常染色体隐性疾病，其特征为感音神经性耳聋、甲状腺肿和碘化物有机化受损。在甲状腺滤泡细胞中，pendrin表达于顶端膜。体外功能数据以及在Pendred综合征患者中观察到的碘化物有机化受损支持pendrin作为顶端碘化物转运体的作用。
