Type 2 iodothyronine deiodinase transgene expression in the mouse heart causes cardiac-specific thyrotoxicosis

Janusz Pachucki, James Hopkins, Robin Peeters, Helen Tu, Suzy D. Carvalho, Helen Kaulbach, E. Dale Abel, Frederic E. Wondisford, Joanne S. Ingwall, P. Reed Larsen

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Type 2 iodothyronine deiodinase (D2) catalyzes intracellular 3, 5, 3′ triiodothyronine (T3) production from thyroxine (T4), 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 D2 expression in the mouse myocardium on cardiac function and gene expression. We prepared transgenic (TG) mice in which human D2 expression was driven by the α-MHC promoter. Despite high myocardial D2 activity, myocardial T3 was, at most, minimally increased in TG myocardium. Although, plasma T3 and T4, 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 α-MHC or SERCA II messenger RNA levels. Biochemical studies and 31P-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 α-MHC.

Original languageEnglish
Pages (from-to)13-20
Number of pages8
JournalEndocrinology
Volume142
Issue number1
DOIs
StatePublished - Mar 12 2001

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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    Pachucki, J., Hopkins, J., Peeters, R., Tu, H., Carvalho, S. D., Kaulbach, H., Dale Abel, E., Wondisford, F. E., Ingwall, J. S., & Reed Larsen, P. (2001). Type 2 iodothyronine deiodinase transgene expression in the mouse heart causes cardiac-specific thyrotoxicosis. Endocrinology, 142(1), 13-20. https://doi.org/10.1210/en.142.1.13