Ritter Megan J, Amano Izuki, Hollenberg Anthony N
Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA.
Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
Endocrinology. 2025 Jan 6;166(2). doi: 10.1210/endocr/bqae164.
Thyroid hormone (TH) is essential throughout life. Its actions are mediated primarily by the thyroid hormone receptor (THR), which is a nuclear receptor. Classically, the THRs act as inducible transcription factors. In the absence of TH, a corepressor complex is recruited to the THR to limit TH-related gene expression. In the presence of TH, the corepressor complex is dismissed and a coactivator complex is recruited to facilitate TH-related gene expression. These coregulators can interact with multiple nuclear receptors and are also key in maintaining normal physiologic function. The nuclear receptor corepressor 1 (NCOR1) and the nuclear receptor corepressor 2 (NCOR2) have been the most extensively studied corepressors of the THR involved in histone deacetylation. The steroid receptor coactivator/p160 (SRC) family and in particular, SRC-1, plays a key role in histone acetylation associated with the THR. The Mediator Complex is also required for pretranscription machinery assembly. This mini-review focuses on how these transcriptional cofactors influence TH-action and signaling, primarily via histone modifications.
甲状腺激素（TH）在整个生命过程中都至关重要。其作用主要由甲状腺激素受体（THR）介导，THR是一种核受体。传统上，THR作为诱导型转录因子发挥作用。在没有TH的情况下，一种共抑制因子复合物会被招募到THR上，以限制与TH相关的基因表达。在有TH的情况下，共抑制因子复合物会被解除，一种共激活因子复合物会被招募来促进与TH相关的基因表达。这些共调节因子可以与多种核受体相互作用，并且在维持正常生理功能中也起着关键作用。核受体共抑制因子1（NCOR1）和核受体共抑制因子2（NCOR2）是参与组蛋白去乙酰化的THR中研究最广泛的共抑制因子。类固醇受体共激活因子/p160（SRC）家族，特别是SRC-1，在与THR相关的组蛋白乙酰化中起关键作用。中介复合物对于转录前机制的组装也是必需的。这篇小型综述主要关注这些转录辅因子如何主要通过组蛋白修饰来影响TH的作用和信号传导。
