Nongenomic Effects of Thyroid Hormones: Their Role in Regulation of the Vascular System

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.