New insights into thyroid hormone action.
New insights into thyroid hormone action.
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DOI：
10.1016/j.pharmthera.2017.02.012
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发表时间：
2017-05
影响因子：
13.5
通讯作者：
Hollenberg AN
中科院分区：
文献类型：
--
作者：
Mendoza A;Hollenberg AN
甲状腺激素（TH）是几乎所有脊椎动物正常发育和功能所必需的内分泌信使。下丘脑-垂体-甲状腺轴被精细地调节以维持循环中几乎恒定的TH（T4和T3）浓度。然而，外周组织和中枢神经系统控制TH的细胞内可用性，这表明TH的循环浓度并不能完全代表每种细胞类型所看到的。事实上，该领域最近的工作已经确定，TH转运蛋白，脱碘酶和甲状腺激素受体辅调节剂可以强烈控制组织特异性的敏感性，以设定量的TH。此外，甲状腺激素受体调节靶基因表达的机制可因基因、组织和细胞背景而异。这篇综述将突出新的见解，控制TH的细胞反应，其中包括独特的信号级联机制。这些发现为异常TH信号引起的人类疾病的病理生理学提供了新的线索。
Thyroid hormones (TH) are endocrine messengers essential for normal development and function of virtually every vertebrate. The hypothalamic-pituitary-thyroid axis is exquisitely modulated to maintain nearly constant TH (T4 and T3) concentrations in circulation. However peripheral tissues and the CNS control the intracellular availability of TH, suggesting that circulating concentrations of TH are not fully representative of what each cell type sees. Indeed, recent work in the field has identified that TH transporters, deiodinases and thyroid hormone receptor coregulators can strongly control tissue-specific sensitivity to a set amount of TH. Furthermore, the mechanism by which the thyroid hormone receptors regulate target gene expression can vary by gene, tissue and cellular context. This review will highlight novel insights into the machinery that controls the cellular response to TH, which include unique signaling cascades. These findings shed new light into the pathophysiology of human diseases caused by abnormal TH signaling.