Braun Doreen, Schweizer Ulrich
Institut für Biochemie und Molekularbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
Institut für Biochemie und Molekularbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
Vitam Horm. 2018;106:19-44. doi: 10.1016/bs.vh.2017.04.005. Epub 2017 Jun 12.
Thyroid hormones orchestrate developmental processes and are among the most important regulators of energy metabolism. Thyroid hormone actions are mostly, but not exclusively, mediated by nuclear hormone receptors. As amino acid derivatives, thyroid hormones need plasma membrane transporters in order to reach their nuclear receptors. Several transporters from different gene families mediate thyroid hormone uptake into cells. Monocarboxylate transporter 8 is a specific thyroid hormone transporter found mutated in patients with severe psychomotor retardation and strangely abnormal thyroid hormone constellations. These patients display a syndrome in which some organs are exposed to increased thyroid hormone signaling, while other organs are lacking thyroid hormone signaling due to complete lack of thyroid hormone uptake. Investigations in many organ systems using mouse models of thyroid hormone transmembrane transporter deficiency have helped complete our picture of thyroid hormone metabolism and action in the body during development and under different physiological conditions. Incorporating the concept of thyroid hormone transmembrane transport has helped understand previously enigmatic drug interactions and may explain how the hormonal set points in the hypothalamus-pituitary-thyroid axis are established.
甲状腺激素调控发育过程，是能量代谢最重要的调节因子之一。甲状腺激素的作用大多（但并非全部）由核激素受体介导。作为氨基酸衍生物，甲状腺激素需要通过质膜转运体才能到达其核受体。来自不同基因家族的几种转运体介导甲状腺激素摄取进入细胞。单羧酸转运体8是一种特异性甲状腺激素转运体，在患有严重精神运动发育迟缓且甲状腺激素水平异常奇怪的患者中发现其发生了突变。这些患者表现出一种综合征，即一些器官暴露于增强的甲状腺激素信号中，而其他器官由于完全缺乏甲状腺激素摄取而缺乏甲状腺激素信号。利用甲状腺激素跨膜转运体缺陷小鼠模型对许多器官系统进行的研究，有助于完善我们对甲状腺激素在发育过程中和不同生理条件下在体内的代谢及作用的认识。纳入甲状腺激素跨膜转运的概念有助于理解以前难以解释的药物相互作用，并可能解释下丘脑 - 垂体 - 甲状腺轴中激素设定点是如何建立的。
