Amiodarone, a powerful antiarrhythmic drug, may exert its effect by antagonism 
of the thyroid hormone, probably at the receptor level. The aim of this study 
was to investigate whether amiodarone affects the levels of thyroid hormone 
receptor (TR) messenger RNA (mRNA) subtypes in mouse hearts. Mice were treated 
with 10, 25, and 50 mg/kg body weight (BW) amiodarone or vehicle 
(propyleneglycol) intraperitoneally, daily for 14 days. The heart rate 
dose-dependently decreased in the 25 mg/kg BW (p < 0.05) and 50 mg/kg BW (p < 
0.005) amiodarone-treated mice compared with control. Serum T3 levels were 
significantly decreased by 25% (4.2 +/- 0.7 pM) in the 50 mg/kg BW amiodarone 
group in comparison to control (5.6 +/- 1.4 pM; p < 0.05). The serum T4 levels 
were 1.3 times higher in 50 mg/kg BW amiodarone-treated mice (13.2 +/-1.6 pM) 
compared with the control (10.3 +/- 1.3 pM; p < 0.005). Determination of 
TRalpha1, alpha2, beta1, and beta2 mRNA in the heart were performed by reverse 
transcriptase-polymerase chain reaction (RT-PCR)/enzyme-linked immunosorbent 
assay (ELISA). Both in treated and untreated mice, TRalpha2 mRNA had the highest 
density in mouse heart, whereas TRbeta2 mRNA had the lowest density. Amiodarone 
dose-dependently downregulated the levels of TRalpha1 and beta1 mRNA in 
comparison to the control. There were, however, no differences in the TRalpha2 
and TRbeta2 mRNA levels in the mice heart treated with different doses of 
amiodarone in comparison with the control group. In conclusion, this study shows 
that amiodarone subtype selectively downregulates the TR mRNA levels in mouse 
myocardium in a dose-dependent manner. These results support a thyroid 
hormone-dependent action of amiodarone.