Nongenomic Actions of Thyroid Hormones

Nongenomic actions of thyroid hormone do not require a direct interaction of 3,5,30-triiodo-L-thyronine (T3) with the transcriptionally active nuclear receptors TRα and TRβ. A rapid response time is a characteristic of many nongenomic actions; the onset of the majority of these effects is within minutes because the action is independent of gene expression and protein synthesis. While only T3 is able to generate a genomic response, the different nongenomic effects may be activated by either T3 or T4 or by other iodothyronine derivatives such as T2. In the last decade, the discovery of a large number of nongenomic actions of thyroid hormones has increasingly attracted the interest of researchers, and different specific binding sites or receptors for these hormones/messengers have now been described in several cellular compartments, including the external surface of the plasma membrane. The function of nongenomic effects of these hormones has mainly been considered to relate to homeostasis, such as actions on plasma membrane ion transporters or maintenance of the cytoskeleton, but recent evidence supports the existence of crosstalk between nongenomic and genomic effects of the hormone. Further examination of such crosstalk may reveal hitherto unappreciated mechanisms underlying global illnesses, such as cardiovascular diseases, inflammatory and immune diseases, and mechanisms of tumor cell function. Indeed, these new aspects have already improved our understanding of the contributions of nongenomic thyroid hormone actions to the regulation of cancer-related angiogenesis and to cancer cell survival pathways. In the present report, we provide a concise overview of the main observations that define the nongenomic actions of thyroid hormones and give a description of the state of the art