This Article Full Text Full Text (PDF) All Versions of this Article: 19/6/1618    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kinugawa, K. Articles by Long, C. S. Search for Related Content PubMed PubMed Citation Articles by Kinugawa, K. Articles by Long, C. S.

Thyroid Hormone Induces Cardiac Myocyte Hypertrophy in a Thyroid Hormone Receptor ₁-Specific Manner that Requires TAK1 and p38 Mitogen-Activated Protein Kinase

Division of Cardiology (M.R.B., C.S.L.), University of Colorado Health Sciences Center, Cardiology Section (C.S.L.), Denver Health Medical Center, Denver, Colorado 80204

Address all correspondence and requests for reprints to: Carlin S. Long, M.D., 777 Bannock Street, Box 0960, Denver, Colorado 80204. E-mail: clong{at}dhha.org.

Alterations in TR [thyroid hormone (TH) receptor]¹ isoform expression have been reported in models of both physiologic and pathologic cardiac hypertrophy as well as in patients with heart failure. In this report, we demonstrate that TH induces hypertrophy as a direct result of binding to the TR₁ isoform and, moreover, that overexpression of TR₁ alone is also associated with a hypertrophic phenotype, even in the absence of ligand. The mechanism of TH and TR₁-specific hypertrophy is novel for a nuclear hormone receptor and involves the transforming growth factor ß-activated kinase (TAK1) and p38. Mitigating TR₁ effects, both TR₂ and TRß₁ attenuate TR₁-induced myocardial growth and gene expression by diminishing TAK1 and p38 activities, respectively. These findings refine our previous observations on TR expression in the hypertrophied and failing heart and suggest that manipulation of thyroid hormone signaling in an isoform-specific manner may be a relevant therapeutic target for altering the pathologic myocardial program.

NURSA Molecule Pages Link:

Nuclear Receptors:   TRα  |  TRβ  |  RXRα  |  RXRβ  |  RXRγ

Ligands:   Thyroid hormone

This article has been cited by other articles:

				E. Ortega, J. Koska, N. Pannacciulli, J. C Bunt, and J. Krakoff Free triiodothyronine plasma concentrations are positively associated with insulin secretion in euthyroid individuals Eur. J. Endocrinol., February 1, 2008; 158(2): 217 - 221. [Abstract] [Full Text] [PDF]

				I. Irrcher, D. R. Walkinshaw, T. E. Sheehan, and D. A. Hood Thyroid hormone (T3) rapidly activates p38 and AMPK in skeletal muscle in vivo J Appl Physiol, January 1, 2008; 104(1): 178 - 185. [Abstract] [Full Text] [PDF]

				D. D. Belke, B. Gloss, E. A. Swanson, and W. H. Dillmann Adeno-Associated Virus-Mediated Expression of Thyroid Hormone Receptor Isoforms-{alpha}1 and -{beta}1 Improves Contractile Function in Pressure Overload-Induced Cardiac Hypertrophy Endocrinology, June 1, 2007; 148(6): 2870 - 2877. [Abstract] [Full Text] [PDF]

				C. Pantos, I. Mourouzis, C. Xinaris, A. D Kokkinos, K. Markakis, A. Dimopoulos, M. Panagiotou, T. Saranteas, G. Kostopanagiotou, and D. V Cokkinos Time-dependent changes in the expression of thyroid hormone receptor {alpha}1 in the myocardium after acute myocardial infarction: possible implications in cardiac remodelling Eur. J. Endocrinol., April 1, 2007; 156(4): 415 - 424. [Abstract] [Full Text] [PDF]

				M. Salem, P. B. Kenney, C. E. Rexroad 3rd, and J. Yao Microarray gene expression analysis in atrophying rainbow trout muscle: a unique nonmammalian muscle degradation model Physiol Genomics, December 13, 2006; 28(1): 33 - 45. [Abstract] [Full Text] [PDF]

				A. Kenessey and K. Ojamaa Thyroid Hormone Stimulates Protein Synthesis in the Cardiomyocyte by Activating the Akt-mTOR and p70S6K Pathways J. Biol. Chem., July 28, 2006; 281(30): 20666 - 20672. [Abstract] [Full Text] [PDF]

				A. Kenessey, E. A. Sullivan, and K. Ojamaa Nuclear localization of protein kinase C-{alpha} induces thyroid hormone receptor-{alpha}1 expression in the cardiomyocyte Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H381 - H389. [Abstract] [Full Text] [PDF]