Thyroid hormone receptor and IGF1/IGFR systems: Possible relations in the human heart

Thyroid hormone (TH) and Insulin Growth Factor 1 (IGF1) systems both play crucial roles in the regulation of cardiac remodeling and hypertrophy processes. The mediation of this regulation is to be attributed to specific Thyroid Hormone Receptors (TRs) and to the IGF1 Receptor (IGF1R). In humans, two TR genes are expressed in the heart, TRa and TRb. Each gene generates two isoforms: TRa1, TR a2 and TRb1, TRb2. The aim of the present work was to study the local thyroid hormone and IGF1 signaling in human myocardium through the evaluation of the gene expression of TRa1, TR a2, TRb1 and IGF1R among atrial and ventricular biopsies obtained from patients undergoing cardiac surgery. Moreover, we evaluated possible correlations between TR and IGF1/IGF1R systems. Eighteen clinically and biochemically euthyroid patients (age: 68.3±3.2 mean±SEM) without overt heart failure (EF=46.4±2.8 %, LVEDD=54.3±1.2 mm, mean±SEM; NYHA I-II) were enrolled in the study: 13 undergoing aorto-coronary bypass and 5 undergoing valve replacement (aorta/mitral valve). Examination of total RNA, using Real Time PCR (Light Cycler Technology) confirmed the expression of specific mRNAs encoding TRa1, TRa2, TRb1 and both IGF1 and IGF1R. We found that the three TR genes are co-expressed in human atrium and ventricle. The finding of a strong correlation among IGF1R and the three TR gene expression in the atrium (p0.001) and among the three TRs in the atrium (p0.001) suggest the interesting possibility that the two systems, TRs and IGF1R could be also functionally associated.