title: Nongenomic actions of thyroid hormone.
abstract: 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 T3, or have no homologies with TR, such as the plasma membrane receptor on integrin αvβ3. Nongenomic actions initiated at the plasma membrane by T4 via integrin αvβ3 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 TRα isoform mediates T4-dependent regulation of intracellular microfilament organization, contributing to cell and tissue structure. p30 TRα1 is another shortened TR isoform found at the plasma membrane that binds T3 and mediates nongenomic hormonal effects in bone cells. T3 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.
authors.affiliation: Pharmaceutical Research Institute, Albany College of Pharmacy &Health Sciences, One Discovery Drive, Rennselaer, New York 12144, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Davis
authors.affiliation: Dipartimento di Scienze e Tecnologie, Università degli studi del Sannio, Via Port'Arsa 11, 82100, Benevento, Italy.
authors.forename: Fernando
authors.initials: F
authors.lastname: Goglia
authors.affiliation: Department of Microbiology &Physiological Systems, University of Massachusetts Medical School, 368 Plantation Street, Worcester, Massachusetts 01605, USA.
authors.forename: Jack L
authors.initials: JL
authors.lastname: Leonard
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D020033:Protein Isoforms; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D037021:Thyroid Hormone Receptors alpha / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D039302:Integrin alphaVbeta3; D020033:Protein Isoforms; D011988:Receptors, Thyroid Hormone; D037021:Thyroid Hormone Receptors alpha; D014284:Triiodothyronine; D013974:Thyroxine