Flamant Frederic, Gauthier Karine, Samarut Jacques
Laboratory of Molecular Cell Biology, Unité Mixte de Recherche, Centre National de la Recherche Scientifique 5161, Institut National de la Recherche Agronomique 1237, France.
Mol Endocrinol. 2007 Feb;21(2):321-33. doi: 10.1210/me.2006-0035. Epub 2006 Jun 8.
T3 regulates many physiological and developmental processes by binding to thyroid hormone receptors (TRs). This induces a conformational change of DNA-bound TRs that releases corepressors in favor of coactivators. The associated chromatin modifications induce polymerase II recruitment. Mouse genetic studies clarified the respective contribution of each receptor isoform and revealed the important activity of unliganded TRs. They also confirm the paradoxical negative regulation of some promoters by liganded TRs. Recent advances place these molecular events in a broader context of extra- and intracellular regulation: control of ligand availability, changes in the cell sensitivity to T3, nongenomic effects, and cross talks with other signaling pathways contribute to increase the diversity and complexity of thyroid hormones signaling. A promising novel class of TRs synthetic ligands, called STORMs (selective TR modulators), might allow for tissue- and promoter-specific interventions.
T3 通过与甲状腺激素受体（TRs）结合来调节许多生理和发育过程。这会诱导与 DNA 结合的 TRs 发生构象变化，从而释放共抑制因子，转而有利于共激活因子。相关的染色质修饰会诱导聚合酶 II 的募集。小鼠遗传学研究阐明了每种受体亚型的各自作用，并揭示了未结合配体的 TRs 的重要活性。这些研究还证实了结合配体的 TRs 对某些启动子具有矛盾的负调控作用。最近的进展将这些分子事件置于细胞外和细胞内调节的更广泛背景中：配体可用性的控制、细胞对 T3 敏感性的变化、非基因组效应以及与其他信号通路的相互作用，都有助于增加甲状腺激素信号传导的多样性和复杂性。一类有前景的新型 TRs 合成配体，称为 STORMs（选择性 TR 调节剂），可能允许进行组织和启动子特异性干预。
