Alterations in cardiac contractility and gene expression during low-T3 syndrome: prevention with T3.
The low-T3 syndrome is a metabolic response resulting in a decreased serum triiodothyronine (T3) concentration that has uncertain effects on thyroid hormone-responsive gene expression and function. We measured cardiac myocyte gene expression and cardiac contractility in young adult female rats using chronic calorie deprivation as a model of the low-T3 syndrome. Sarcoplasmic reticulum calcium adenosinetriphosphatase (SERCA2) and myosin heavy chain (MHC) isoform mRNA content were measured after 28 days on a 50% calorie-restricted diet (low T3) with or without T3 treatment (6 micrograms.kg body wt-1.day-1). The low-T3 animals had decreased maximal rates of contraction (-13%; P < 0.05) and relaxation (-18%; P < 0.05) compared with the control and the T3-treated groups. There was a 21% (P < 0.05) increase in left ventricular (LV) relaxation time in the low-T3 animals vs. both control and T3-treated groups. The LV content of the SERCA2 mRNA was decreased significantly (37%) in the low-T3 rats and was increased (P < 0.05) with T3 treatment vs. controls. The alpha-MHC mRNA isoform decreased in the low-T3 animals but was unchanged in the T3-treated animals. T3 supplementation normalized both cardiac function and phenotype of calorie-restricted animals, suggesting a role for the low-T3 syndrome in the pathophysiological response to calorie restriction.
Katzeff
H L
HL
Department of Medicine, North Shore University Hospital, Manhasset, New York 10030, USA.
Powell
S R
SR
Ojamaa
K
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis*; D004038:Diet, Reducing; D005067:Euthyroid Sick Syndromes / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D007037:Hypothyroidism / Q000503:physiopathology; D009200:Myocardial Contraction / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013974:Thyroxine / Q000097:blood; D014158:Transcription, Genetic / Q000187:drug effects; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects; D015430:Weight Gain
D014284:Triiodothyronine; D000252:Calcium-Transporting ATPases; D013974:Thyroxine