Abstract—

The nongenomic effects of thyroid hormones (THs) develop within minutes or hours and do not depend on the binding of the hormone to the transcriptionally active nuclear receptors TRα and TRβ. These effects are characterized by a variety of receptors and signaling pathways involved, which may be distinct in different cell types. Thyroxin (T₃) or triiodthyronine (T₄) can induce a nongenomic effect by association with transcriptionally inactive TRα and TRβ in the cell cytoplasm, their truncated isoforms, or αvβ3 integrin. With nongenomic action, as well as with genomic action, T₃ and T₄ can alter gene transcription, but their influence is extended to a wider spectrum of genes in this case. The nongenomic effects of THs often complement the genomic ones, causing similar changes in cell activity, or enhance them by providing TRα and TRβ translocation into the nucleus or their posttranslational modification. The nongenomic effects of THs on the vasculature include angiogenesis and rapid vasodilation. The key signaling cascade mediating angiogenesis includes αvβ3 integrin, protein kinase D, and histone deacetylase 5. The mechanisms of rapid vasodilation are still poorly understood and may vary in different regions of the vascular bed. In cytoplasm of endothelial cells, the nongenomic effect of THs is mediated by TRα1, PI3K, and NO synthase, although this mechanism is not universal. TH-induced vasodilation of skeletal muscle arteries includes the participation of αvβ3 integrin located in smooth muscle cells, but the signaling cascades triggered by it have not yet been studied. Knowledge of the molecular mechanisms of the nongenomic effect of thyroid hormones is important for the development of new methods of pharmacological correction of vascular pathologies, which are usually associated with thyroid disorders.

中文翻译：

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甲状腺激素的非基因组效应：在血管系统调节中的作用。

摘要-

甲状腺激素（THs）的非基因组效应可在数分钟或数小时内产生，并且不依赖于激素与转录活性核受体TRα和TRβ的结合。这些作用的特点是涉及多种受体和信号传导途径，在不同细胞类型中可能不同。甲状腺素（T ₃）或三碘甲状腺素（T ₄）可以通过与细胞质中的转录失活的TRα和TRβ，其截短的亚型或αvβ3整联蛋白结合而诱导非基因组效应。在非基因组作用以及基因组作用下，T ₃和T ₄可以改变基因的转录，但是在这种情况下，它们的影响会扩展到更广泛的基因范围。TH的非基因组效应通常会补充基因组效应，从而引起类似的细胞活性变化，或者通过提供TRα和TRβ易位进入细胞核或其翻译后修饰来增强它们。TH对血管系统的非基因组作用包括血管生成和快速血管舒张。介导血管生成的关键信号级联反应包括αvβ3整联蛋白，蛋白激酶D和组蛋白脱乙酰基酶5。快速血管舒张的机制仍知之甚少，并且可能在血管床的不同区域发生变化。在内皮细胞的细胞质中，THs的非基因组效应是由TRα1，PI3K和NO合酶介导的，尽管这种机制并不普遍。TH诱导的骨骼肌动脉血管舒张包括参与位于平滑肌细胞中的αvβ3整联蛋白的参与，但尚未研究由其触发的信号级联反应。甲状腺激素非基因组作用的分子机制的知识对于开发通常与甲状腺疾病有关的血管病变的药理校正新方法的开发很重要。