Thyroid hormone receptor alpha1 (TRalpha1) is predominantly expressed in the 
myocardium but its biological function under physiological or pathological 
conditions remains largely unknown. The present study investigated possible 
interactions between alpha1 adrenergic and thyroid hormone signaling at the 
level of TRalpha1, potential underlying mechanisms and physiological 
consequences, as well as the role of TRalpha1 in cell differentiation. This may 
be of physiological relevance since both thyroid hormone and adrenergic 
signalling are implicated in the pathophysiology of cardiac remodelling. 
Neonatal cardiomyocytes obtained from newborn rats (2-3 days) were exposed to 
phenylephrine (PE, an alpha1 adrenergic agonist) for 5 days, in the absence or 
excess of T3 in the culture medium. PE, in the absence of T3, resulted in 5.0 
fold increase in TRalpha1 expression in nucleus and 2.0 fold decrease in 
TRalpha1 expression in cytosol, P<0.05. As a result, a fetal pattern of myosin 
isoform expression with marked expression of beta-MHC was observed in PE treated 
vs the untreated cells, P<0.05. PD98059 (an ERK signalling inhibitor) abrogated 
this response. In the presence of T3 in the culture medium, TRalpha1 expression 
was increased 1.6 fold in nucleus and 2.0 fold in cytosol in PE-T3 vs PE treated 
cells, P<0.05, and the fetal pattern of myosin isoform expression was prevented. 
Parallel studies with H9c2 myoblasts showed that reduction of T3 binding to 
TRalpha1 receptor delayed cardiac myoblasts differentiation without affecting 
proliferation. In conclusion, in neonatal cardiomyocytes, nuclear TRalpha1 is 
overexpressed after prolonged activation of the alpha1- adrenergic signalling by 
PE. This response seems to be an ERK kinase dependent process. Over-expression 
of TRalpha1 may lead to fetal cardiac phenotype in the absence of thyroid 
hormone availability. Furthermore, TRalpha1 seems to be critical in cardiac 
myoblast differentiation.