Schweizer Ulrich, Köhrle Josef
Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Biochim Biophys Acta. 2013 Jul;1830(7):3965-73. doi: 10.1016/j.bbagen.2012.07.015. Epub 2012 Aug 7.
Iodothyronines are charged amino acid derivatives that cannot passively cross a phospholipid bilayer. Transport of thyroid hormones across plasma membranes is mediated by integral membrane proteins belonging to several gene families. These transporters therefore allow or limit access of thyroid hormones into brain. Since thyroid hormones are essential for brain development and cell differentiation, it is expected that genetic deficiency of such transporters would result in neurodevelopmental derangements.
We introduce concepts of thyroid hormone transport into the brain and into brain cells. Important thyroid hormone transmembrane transporters are presented along with their expression patterns in different brain cell types. A focus is placed on monocarboxylate transporter 8 (MCT8) which has been identified as an essential thyroid hormone transporter in humans. Mutations in MCT8 underlie one of the first described X-linked mental retardation syndromes, the Allan-Herndon-Dudley syndrome.
Thyroid hormone transporter molecules are expressed in a developmental and cell type-specific pattern. Any thyroid hormone molecule has to cross consecutively the luminal and abluminal membranes of the capillary endothelium, enter astrocytic foot processes, and leave the astrocyte through the plasma membrane to finally cross another plasma membrane on its way towards its target nucleus.
We can expect more transporters being involved in or contributing to in neurodevelopmental or neuropsychiatric disease. Due to their expression in cellular components regulating the hypothalamus-pituitary-thyroid axis, mutations and polymorphisms are expected to impact on negative feedback regulation and hormonal setpoints. This article is part of a Special Issue entitled Thyroid hormone signalling.
碘甲状腺原氨酸是带电荷的氨基酸衍生物，不能被动穿过磷脂双分子层。甲状腺激素跨质膜的转运由属于几个基因家族的整合膜蛋白介导。因此，这些转运蛋白允许或限制甲状腺激素进入大脑。由于甲状腺激素对大脑发育和细胞分化至关重要，预计此类转运蛋白的基因缺陷会导致神经发育紊乱。
我们介绍了甲状腺激素向大脑和脑细胞转运的概念。展示了重要的甲状腺激素跨膜转运蛋白及其在不同脑细胞类型中的表达模式。重点关注单羧酸转运蛋白8（MCT8），它已被确定为人类必需的甲状腺激素转运蛋白。MCT8突变是最早描述的X连锁智力障碍综合征之一——艾伦 - 赫恩登 - 达德利综合征的病因。
甲状腺激素转运蛋白分子以发育和细胞类型特异性模式表达。任何甲状腺激素分子都必须依次穿过毛细血管内皮的管腔膜和管腔外膜，进入星形胶质细胞的足突，并通过质膜离开星形胶质细胞，最终在其前往靶细胞核的途中穿过另一质膜。
我们可以预期会有更多转运蛋白参与神经发育或神经精神疾病或对此类疾病有影响。由于它们在下丘脑 - 垂体 - 甲状腺轴调节细胞成分中的表达，预计突变和多态性会影响负反馈调节和激素设定点。本文是名为“甲状腺激素信号传导”的特刊的一部分。
