Friesema Edith C H, Jansen Jurgen, Heuer Heike, Trajkovic Marija, Bauer Karl, Visser Theo J
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
Nat Clin Pract Endocrinol Metab. 2006 Sep;2(9):512-23. doi: 10.1038/ncpendmet0262.
The actions and the metabolism of thyroid hormone are intracellular events that require the transport of iodothyronines across the plasma membrane. It is increasingly clear that this process does not occur by simple diffusion, but is facilitated by transport proteins. Only recently have iodothyronine transporters been identified at the molecular level, of which organic anion transporting polypeptide 1C1 and monocarboxylate transporter 8 (MCT8) deserve special mention, because of their high activity and specificity for iodothyronines. Organic anion transporting polypeptide 1C1 is almost exclusively expressed in brain capillaries, and may be crucial for the transport of the prohormone T4 across the blood-brain barrier. MCT8 is also expressed in the brain--in particular, in neurons--but also in other tissues. MCT8 seems to be especially important for the uptake of active hormone T3 into neurons, which is essential for optimal brain development. T3 is produced from T4 by type 2 deiodinase in neighboring astrocytes. Neurons express type 3 deiodinase, the enzyme that terminates T3 activity. The SLC16A2 (formerly MCT8) gene is located on chromosome Xq13.2 and has recently been associated with a syndrome combining severe, X-linked, psychomotor retardation and high serum T3 levels. In over 20 families, where affected males have developed this syndrome, several mutations in MCT8 have been identified. The disease mechanism is thought to involve a defect in the neuronal entry of T3 and, therefore, in the action and metabolism of T3 in these cells. This defect results in impaired neurological development and a decrease in T3 clearance.
甲状腺激素的作用和代谢是细胞内事件，需要碘甲状腺原氨酸穿过质膜进行转运。越来越清楚的是，这个过程不是通过简单扩散发生的，而是由转运蛋白促进的。直到最近，碘甲状腺原氨酸转运体才在分子水平上被鉴定出来，其中有机阴离子转运多肽1C1和单羧酸转运体8（MCT8）值得特别提及，因为它们对碘甲状腺原氨酸具有高活性和特异性。有机阴离子转运多肽1C1几乎只在脑毛细血管中表达，可能对激素原T4穿过血脑屏障的转运至关重要。MCT8也在脑中表达——特别是在神经元中——但也在其他组织中表达。MCT8似乎对活性激素T3进入神经元特别重要，这对最佳脑发育至关重要。T3由邻近星形胶质细胞中的2型脱碘酶从T4产生。神经元表达3型脱碘酶，该酶可终止T3的活性。SLC16A2（以前称为MCT8）基因位于X染色体q13.2上，最近与一种严重的X连锁精神运动发育迟缓合并高血清T3水平的综合征相关。在20多个受影响男性患此综合征的家族中，已鉴定出MCT8的几种突变。疾病机制被认为涉及T3进入神经元的缺陷，因此也涉及这些细胞中T3的作用和代谢。这种缺陷导致神经发育受损和T3清除率降低。
