TRs Have Common and Isoform-Specific Functions in Regulation of the Cardiac Myosin Heavy Chain Genes

Author:

Mansén Anethe1,Yu Fushun23,Forrest Douglas4,Larsson Lars23,Vennström Björn1

Affiliation:

1. Department of Cell and Molecular Biology (A.M., B.V.), S-171 77 Stockholm, Sweden

2. Department of Clinical Neuroscience (F.U., L.L.), Karolinska Institute, S-171 77 Stockholm, Sweden

3. Noll Physiological Research Center and Department of Cellular and Molecular Physiology (F.U., L.L.), Pennsylvania State University, University Park, Pennsylvania 16802;

4. Department of Human Genetics (D.F.), Mount Sinai School of Medicine, New York, New York 10029

Abstract

Abstract TRα1 and TRβ mediate the regulatory effects of T3 and have profound effects on the cardiovascular system. We have analyzed the expression of the cardiac myosin heavy chain (MyHC) genesα and β in mouse strains deficient for one or several TR genes to identify specific regulatory functions of TRα1 and TRβ. The results show that TRα1 deficiency, which slows the heart rate, causes chronic overexpression of MyHCβ. However, MyHCβ was still suppressible by T3 in both TRα1- and TRβ-deficient mice, indicating that either receptor can mediate repression of MyHCβ. T3-dependent induction of the positively regulated MyHCα gene was similar in both TRα1- and TRβ-deficient mice. The data identify a specific role for TRα1 in the negative regulation of MyHCβ, whereas TRα1 and TRβ appear interchangeable for hormone-dependent induction of MyHCα. This suggests that TR isoforms exhibit distinct specificities in the genes that they regulate within a given tissue type. Thus, dysregulation of MyHCβ is likely to contribute to the critical role of TRα1 in cardiac function.

Publisher

The Endocrine Society

Subject

Endocrinology,Molecular Biology,General Medicine

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