Негеномное действие тиреоидных гормонов: роль в регуляции сосудистой системы

The nongenomic effects of thyroid hormones 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. T 3 or T 4 can induce nongenomic effect by association with transcriptionally inactive TRα and TRβ in the cytoplasm of the cell, their truncated isoforms or integrin αvβ3. With nongenomic action, as well as with genomic action, T 3 and T 4 can alter gene transcription, but in this case, their influence is extended to wider spectrum of genes. The nongenomic effects of thyroid hormones 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 post-translational modification. The nongenomic effects of thyroid hormones on the vasculature include angiogenesis and rapid vasodilation. The key signaling cascade mediating angiogenesis includes integrin αvβ3, 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 thyroid hormones is mediated by TRα1, PI3K, and NO synthase, but this mechanism is not universal. Thyroid hormones-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.