Nongenomic actions of thyroid hormone

The nongenomic actions of thyroid hormone begin at receptors in the plasma membrane, mitochondria or cytoplasm. These receptors can share structural homologies with nuclear thyroid hormone receptors (TRs) that mediate transcriptional actions of T-3, or have no homologies with TR, such as the plasma membrane receptor on integrin alpha v beta(3). Nongenomic actions initiated at the plasma membrane by T-4 via integrin alpha v beta(3) can induce gene expression that affects angiogenesis and cell proliferation, therefore, both nongenomic and genomic effects can overlap in the nucleus. In the cytoplasm, a truncated TR alpha isoform mediates T-4-dependent regulation of intracellular microfilament organization, contributing to cell and tissue structure. p30 TR alpha 1 is another shortened TR isoform found at the plasma membrane that binds T-3 and mediates nongenomic hormonal effects in bone cells. T-3 and 3,5-diiodo-L-thyronine are important to the complex nongenomic regulation of cellular respiration in mitochondria. Thus, nongenomic actions expand the repertoire of cellular events controlled by thyroid hormone and can modulate TR-dependent nuclear events. Here, we review the experimental approaches required to define nongenomic actions of the hormone, enumerate the known nongenomic effects of the hormone and their molecular basis, and discuss the possible physiological or pathophysiological consequences of these actions.