Leibniz Institute for Age Research/Fritz Lipmann Institute, Jena, Germany.
Eur Thyroid J. 2012 Jul;1(2):72-9. doi: 10.1159/000339474. Epub 2012 Jun 20.
Thyroid hormone (TH) metabolism and action via binding to nuclear receptors are intracellular events that require the passage of TH across the plasma membrane. This process is mediated by specific TH transporters of which the monocarboxylate transporter 8 (Mct8) has received major attention. Mct8 is highly expressed in different tissues such as liver, kidney, thyroid, pituitary and brain. In humans, inactivating mutations of the MCT8 gene (SLC16A2) are associated with severe forms of psychomotor retardation and abnormal TH serum levels (Allan-Herndon-Dudley syndrome). Surprisingly, Mct8 knockout (ko) mice do not exhibit overt neurological symptoms but fully replicate the unusual serum TH profile with highly increased serum T3 in the presence of low serum T4. In order to evaluate the underlying mechanisms for these abnormalities, TH transport and metabolism have been intensively studied in different tissues of Mct8 ko mice. Here, we summarize the observed changes within the hypothalamus-pituitary-thyroid axis that result in altered TH production and secretion. Although analysis of Mct8 ko mice has greatly expanded our knowledge, many open questions still remain to be addressed in order to define the tissue- and cell-specific role of this important TH transporter.
甲状腺激素（TH）通过与核受体结合而发挥作用的代谢是细胞内事件，需要 TH 穿过质膜。这个过程由特定的 TH 转运蛋白介导，其中单羧酸转运蛋白 8（Mct8）受到了极大的关注。Mct8 在不同的组织中高度表达，如肝脏、肾脏、甲状腺、垂体和大脑。在人类中，Mct8 基因（SLC16A2）的失活突变与严重的精神运动发育迟缓以及异常的 TH 血清水平（Allan-Herndon-Dudley 综合征）有关。令人惊讶的是，Mct8 敲除（ko）小鼠并没有表现出明显的神经症状，但在存在低血清 T4 的情况下，完全复制了异常的血清 TH 谱，血清 T3 显著升高。为了评估这些异常的潜在机制，已经在 Mct8 ko 小鼠的不同组织中对 TH 转运和代谢进行了深入研究。在这里，我们总结了在下丘脑-垂体-甲状腺轴中观察到的变化，这些变化导致 TH 产生和分泌的改变。尽管对 Mct8 ko 小鼠的分析极大地扩展了我们的知识，但仍有许多悬而未决的问题需要解决，以确定这个重要的 TH 转运蛋白在组织和细胞特异性中的作用。
