Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Endocr Rev. 2020 Apr 1;41(2). doi: 10.1210/endrev/bnz008.
Thyroid hormone transporters at the plasma membrane govern intracellular bioavailability of thyroid hormone. Monocarboxylate transporter (MCT) 8 and MCT10, organic anion transporting polypeptide (OATP) 1C1, and SLC17A4 are currently known as transporters displaying the highest specificity toward thyroid hormones. Structure-function studies using homology modeling and mutational screens have led to better understanding of the molecular basis of thyroid hormone transport. Mutations in MCT8 and in OATP1C1 have been associated with clinical disorders. Different animal models have provided insight into the functional role of thyroid hormone transporters, in particular MCT8. Different treatment strategies for MCT8 deficiency have been explored, of which thyroid hormone analogue therapy is currently applied in patients. Future studies may reveal the identity of as-yet-undiscovered thyroid hormone transporters. Complementary studies employing animal and human models will provide further insight into the role of transporters in health and disease. (Endocrine Reviews 41: 1 - 55, 2020).
甲状腺激素转运体位于质膜上，调节甲状腺激素的细胞内生物利用度。单羧酸转运蛋白 8 和 10（MCT8 和 MCT10）、有机阴离子转运多肽 1C1（OATP1C1）和溶质载体家族 17 成员 4（SLC17A4）是目前已知对甲状腺激素具有最高特异性的转运体。利用同源建模和突变筛选的结构功能研究，使我们更好地理解了甲状腺激素转运的分子基础。MCT8 和 OATP1C1 的突变与临床疾病有关。不同的动物模型为甲状腺激素转运体，特别是 MCT8 的功能作用提供了深入了解。目前已经探索了针对 MCT8 缺乏症的不同治疗策略，其中甲状腺激素类似物治疗已应用于患者。未来的研究可能会揭示尚未发现的甲状腺激素转运体的身份。采用动物和人类模型的补充研究将进一步深入了解转运体在健康和疾病中的作用。（内分泌评论 41: 1-55, 2020）。
