BACKGROUND: We reported previously that left ventricular gene expression for 
thyrotropin-releasing hormone (TRH) precursor was increased in rats with heart 
failure 8 weeks after myocardial infarction (MI) and that early ACE inhibition 
tended to cause further myocardial induction of this gene.
METHODS AND RESULTS: Here, we show that after MI, the expression of pro-TRH is 
induced in the heart coordinately with the protease PC1, an important enzyme in 
TRH biosynthesis. Pro-TRH gene expression was induced in cardiac interstitial 
cells after MI, and this effect was restricted to the heart, because no increase 
in TRH mRNA abundance was observed in the hypothalamus, kidney, or lung. 
Transcript abundance of pro-TRH can be increased in cultured cardiac fibroblasts 
by several adrenergic agonists, indicating that the adrenergic axis may play a 
regulatory role in cardiac TRH production. Acute intravenous administration of 
TRH to rats with ischemic cardiomyopathy caused a significant increase in heart 
rate, mean arterial pressure, cardiac output, stroke volume, and cardiac 
contractility.
CONCLUSIONS: Taken together, these results indicate that TRH is specifically 
induced in the heart after MI and that it can increase cardiac performance in 
rats with ischemic cardiomyopathy. Thus, in addition to catecholamine and 
angiotensin II, pro-TRH/TRH may be another important axis that affects 
hemodynamics and cardiac function in heart failure.