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

doi:10.1210/en.142.1.13

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 journal › Article › peer-review

55 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 language	English (US)
Pages (from-to)	13-20
Number of pages	8
Journal	Endocrinology
Volume	142
Issue number	1
DOIs	https://doi.org/10.1210/en.142.1.13
State	Published - 2001
Externally published	Yes

ASJC Scopus subject areas

Endocrinology
Endocrinology, Diabetes and Metabolism

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title = "Type 2 iodothyronine deiodinase transgene expression in the mouse heart causes cardiac-specific thyrotoxicosis",

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.",

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

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doi = "10.1210/en.142.1.13",

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AU - Pachucki, Janusz

AU - Hopkins, James

AU - Peeters, Robin

AU - Tu, Helen

AU - Carvalho, Suzy D.

AU - Kaulbach, Helen

AU - Dale Abel, E.

AU - Wondisford, Frederic E.

AU - Ingwall, Joanne S.

AU - Reed Larsen, P.

PY - 2001

Y1 - 2001

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AB - 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.

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

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