title: Nongenomic actions of thyroid hormone on the heart.
abstract: Extranuclear or nongenomic actions of thyroid hormone do not require formation of a nuclear complex between the hormone and its traditional 3,5,3'-triiodo-L-thyronine (T3) receptor (TR). Among nongenomic actions of iodothyronines that are relevant to the heart are those on membrane ion channels or pumps. These include stimulation of the sarcolemmal Na+ channel, inward-rectifying K+ channel, voltage-activated potassium channels, and calcium pump (Ca2+-adenosine triphosphatases [ATPases]) and have been shown in intact cells or isolated membranes. Because circulating levels of thyroid hormone are relatively stable, actions on channels or pumps may contribute to setting of basal activity of these transport functions. The mechanism of certain of these membrane effects may involve actions of the hormone on signal transducing protein kinases that modulate levels of activity of plasma membrane channels. Thyroid hormone nongenomically enhances myocardial contractility in isolated myocardial cells, in the isolated perfused rat heart and in human subjects. Iodothyronines also decrease vasomotor tone in a variety of models and in man by a mechanism independent of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), or nitric oxide generation. Acutely increased myocardial mitochondrial respiration has been demonstrated in isolated organelles exposed to thyroid hormone. Genomic and nongenomic actions of thyroid hormone can interface, e.g., at the level of sarcoplasmic reticulum Ca2+-ATPase, where gene expression is regulated by the TR-T3 complex and activity of the enzyme can be modulated nongenomically. The relevance of nongenomic actions of thyroid hormone on the heart has been demonstrated in acute effects of the hormone on cardiac output and systemic vascular resistance in human subjects.
authors.affiliation: Ordway Research Institute, Albany Medical College and Stratton Veterans Affairs Medical Center, Albany, New York, USA. pjdavis@albany.net
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Davis
authors.forename: Faith B
authors.initials: FB
authors.lastname: Davis
mesh_terms: D000818:Animals; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051381:Rats; D013963:Thyroid Hormones / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D014284:Triiodothyronine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology
chemical_list: D013963:Thyroid Hormones; D014284:Triiodothyronine