title: The Impact of a Non-Functional Thyroid Receptor Beta upon Triiodotironine-Induced Cardiac Hypertrophy in Mice.
abstract: OBJECTIVE
  Thyroid hormone (TH) signalling is critical for heart function. The heart expresses thyroid hormone receptors (THRs); THRα1 and THRβ1. We aimed to investigate the regulation mechanisms of the THRβ isoform, its association with gene expression changes and implications for cardiac function.
  
  
  METHODS
  The experiments were performed using adult male mice expressing TRβΔ337T, which contains the Δ337T mutation of the human THRB gene and impairs ligand binding. Cardiac function and RNA expression were studied after hypo-or hyperthyroidism inductions. T3-induced cardiac hypertrophy was not observed in TRβΔ337T mice, showing the fundamental role of THRβ in cardiac hypertrophy.
  
  
  RESULTS
  We identified a group of independently regulated THRβ genes, which includes Adrb2, Myh7 and Hcn2 that were normally regulated by T3 in the TRβΔ337T group. However, Adrb1, Myh6 and Atp2a2 were regulated via THRβ. The TRβΔ337T mice exhibited a contractile deficit, decreased ejection fraction and stroke volume, as assessed by echocardiography. In our model, miR-208a and miR-199a may contribute to THRβ-mediated cardiac hypertrophy, as indicated by the absence of T3-regulated ventricular expression in TRβΔ337T mice.
  
  
  CONCLUSIONS
  THRβ has important role in the regulation of specific mRNA and miRNA in T3-induced cardiac hypertrophic growth and in the alteration of heart functions.
authors: Laboratx00F3;rio de Endocrinologia Translacional, IBCCF, UFRJ, Rio de Janeiro, Brasil.
authors: Güínever Eustáquio
authors: GE
authors: do Império
authors: Isalira Peroba
authors: IP
authors: Ramos
authors: Letícia Aragão
authors: LA
authors: Santiago
authors: Guilherme Faria
authors: GF
authors: Pereira
authors: Norma Aparecida
authors: NA
authors: dos Santos Almeida
authors: Cesar Seigi
authors: CS
authors: Fuziwara
authors: Carmen C
authors: CC
authors: Pazos-Moura
authors: Edna Teruko
authors: ET
authors: Kimura
authors: Emerson Lopes
authors: EL
authors: Olivares
authors: Tania Maria
authors: TM
authors: Ortiga-Carvalho
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D006980:Hyperthyroidism / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D007037:Hypothyroidism / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics; D009154:Mutation; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D014284:Triiodothyronine / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D035683:MicroRNAs; C534780:Mirn199 microRNA, mouse; C543978:Mirn208 microRNA, mouse; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine