Type 2 iodothyronine deiodinase (D(2)) catalyzes intracellular 3, 5, 3' 
triiodothyronine (T(3)) production from thyroxine (T(4)), and its messenger RNA 
mRNA is highly expressed in human, but not rodent, myocardium. The goal of this 
study was to identify the effects of D(2) expression in the mouse myocardium on 
cardiac function and gene expression. We prepared transgenic (TG) mice in which 
human D(2) expression was driven by the alpha-MHC promoter. Despite high 
myocardial D(2) activity, myocardial T(3) was, at most, minimally increased in 
TG myocardium. Although, plasma T(3) and T(4), growth rate as well as the heart 
weight was not affected by TG expression, there was a significant increase in 
heart rate of the isolated perfused hearts, from 284 +/-12 to 350 +/- 7 
beats/min. This was accompanied by an increase in pacemaker channel (HCN2) but 
not alpha-MHC or SERCA II messenger RNA levels. Biochemical studies and 
(31)P-NMR spectroscopy showed significantly lower levels of phosphocreatine and 
creatine in TG hearts. These results suggest that even mild chronic myocardial 
thyrotoxicosis, such as may occur in human hyperthyroidism, can cause 
tachycardia and associated changes in high energy phosphate compounds 
independent of an increase in SERCA II and alpha-MHC.