Besides the well-characterized genomic action of thyroid hormone (TH), mediated 
by thyroid hormone receptors (TRs), accumulating data support the so-called 
non-genomic action of TH, which is often related to activation of signalling 
pathways. In this study, we sought to determine whether TH activates 
intracellular signalling pathways in the adult cardiac myocytes and whether such 
activation modulates cell growth and the expression of target proteins important 
in cardiac function. We demonstrate that TH promotes a rapid increase in the 
phosphorylation of several kinases, ERK1/2, PKCdelta, p38-MAPK and Akt. This 
activation is inhibited by triiodothyroacetic acid (triac), which is a TH 
analogue known to displace the hormone from membrane bound receptors, indicating 
that this TH effect is mediated through a cell membrane-initiated mechanism. 
Furthermore, using specific inhibitors of the TH-activated kinases, we show that 
the long-term effects of TH on the expression of sarcoplasmic reticulum 
Ca(2+)-ATPase (SERCA), alpha- and beta-myosin heavy chain (MHC) and cell growth 
are reverted, implying that what is initiated as a non-genomic action of the 
hormone interfaces with genomic effects. These data provide further insights 
into the underlying mechanisms of TH action in the heart with potentially 
important implications in the management of cardiac pathology.