title: The role of thyroid hormone nuclear receptors in the heart: evidence from pharmacological approaches.
abstract: This review evaluates the hypothesis that the cardiac effects of amiodarone can be explained-at least partly-by the induction of a local 'hypothyroid-like condition' in the heart. Evidence supporting the hypothesis comprises the observation that amiodarone exerts an inhibitory effect on the binding of T3 to thyroid hormone receptors (TR) alpha-1 and beta-1 in vitro, and on the expression of particular T3-dependent genes in vivo. In the heart, amiodarone decreases heart rate and alpha myosin heavy chain expression (mediated via TR alpha-1), and increases sarcoplasmic reticulum calcium-activated ATPase and beta myosin heavy chain expression (mediated via TR beta-1). Recent data show a significant similarity in expression profiles of 8,435 genes in the heart of hypothyroid and amiodarone-treated animals, although similarities do not always exist in transcripts of ion channel genes. Induction of a hypothyroid cardiac phenotype by amiodarone may be advantageous by decreasing energy demands and increasing energy availability.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. w.m.wiersinga@amc.uva.nl
authors.forename: Wilmar M
authors.initials: WM
authors.lastname: Wiersinga
mesh_terms: D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: D000889:Anti-Arrhythmia Agents; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D018995:Myosin Heavy Chains; D000638:Amiodarone