《生命科学》 2013, 25(2): 176-183
摘 要:摘 要:甲状腺激素对生长、分化、发育和保持代谢平衡有着深远的影响。这种影响主要是通过结合甲状腺激素受体(thyroid hormone receptor, TR) 并调控TR 的靶基因的转录而实现的。机体还可以通过多种方式对TR 的转录活性进行调控,如不同的TR 异构体、各种甲状腺激素反应元件、不同的异二聚体、辅助调控因子以及TR 的细胞定位等。甲状腺激素可以影响多种关键糖脂代谢通路早已被人们所了解。由于甲状腺激素可以降低胆固醇,改善血脂和减肥,人们研发了许多甲状腺激素模拟物。其中一些甲状腺激素模拟物已被用于临床试验,但是由于甲状腺激素复杂的生理效应,这些模拟物的分子作用机制并不完全清楚。本文将根据最近的一些人群研究、甲状腺激素模拟物的临床研究和TR 动物模型研究的进展,对甲状腺激素调控代谢的作用及其分子机制进行小结。
关键词:甲状腺激素;甲状腺激素受体;代谢调控
Abstract: Abstract: Thyroid hormone plays critical roles in growth, differentiation, development and maintenance of metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the expression of TR target genes. The transcriptional activity of TRs is modulated by multiple factors including the diversity of TR isoforms and thyroid hormone response elements, different heterodimeric partners, a host of coregulators, and the cellular location of TRs. The concept that thyroid hormone influences diverse metabolic pathways, which are important for lipid and glucose metabolism, has been recognized for decades. Thyroid hormone mimetics have been developed since thyroid hormone can lower cholesterol, improve serum lipid profiles and treat obesity. Although some thyroid hormone mimetics have already been used in human trials, we still do not understand the exact molecular mechanism due to the complex physiological effects of thyroid hormone. In the present review, we summarize the recent advance in understanding the molecular mechanisms of thyroid hormone action in metabolic regulations obtained from human subject research, thyroid hormone mimetics and their application, and TR mouse models study.
Key words: thyroid hormone; thyroid hormone receptor; metabolic regulation