Background: The myosin heavy chain (MHC) genes are regulated by triiodothyronine (T3) in a reciprocal and chamber-specific manner. To further our understanding of the potential mechanisms involved, we determined the T3 responsiveness of the MHC genes, α and β, and the β-MHC antisense (AS) gene in the rat ventricles and atria.
Methods: Hypothyroid rats were administered a single physiologic (1 μg) or pharmacologic (20 μg) dose of T3, and sequential measurements of β-MHC hn- and AS RNA and α-MHC heterogeneous nuclear RNA from rat ventricular and atrial myocardium were performed with reverse transcription PCR.
Results: We have demonstrated that T3 treatment increases the myocyte content of an AS β-MHC RNA in atria and ventricles that includes sequences complementary to both the first 5′ and last 3′ introns of the β-MHC sense transcript. In the hypothyroid rat ventricle, β-MHC sense RNA expression is maximal, while in the euthyroid rat ventricle, β-MHC AS RNA is maximal. β-MHC AS expression increased by 52 ± 9.8% at the peak, 24 hours after injection of a physiologic dose of T3 (1 μg/animal), while β-MHC sense RNA decreased by 41 ± 2.2% at 36 hours, the nadir. In hypothyroid atria, β-MHC AS RNA was induced by threefold within 6 hours of administration of 1 μg T3, demonstrating that in the atria, β-MHC AS expression is regulated by T3, while α-MHC expression is not.
Conclusions: In the hypothyroid rat heart ventricle, β-MHC AS RNA expression increases in response to T3 similar to that of α-MHC. Simultaneous measures of β-MHC sense RNA are decreased, suggesting a possible mechanism for AS to regulate sense expression. In atria, while α-MHC is not influenced by thyroid state, β-MHC sense and AS RNA were simultaneously and inversely altered in response to T3. This confirms a close positive relationship between T3 and β-MHC AS RNA in both the atria and ventricles, while demonstrating for the first time that α- and β-MHC expression is not coupled in the atria.
