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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on May 17, 2004; DOI: 10.1124/jpet.104.069153


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Received for publication March 30, 2004.
Revised May 17, 2004.
Accepted for publication May 17, 2004.

Regulation of Gene Expression in Cardiomyocytes by Thyroid Hormone and Thyroid Hormone Analogs, 3,5-Diiodothyropropionic Acid and CGS 23425

Cynthia R Adamson 1*, Niranjan Maitra 1, Joseph John Bahl 1, Kevin Greer 1, Scott Klewar 1, James Hoying 1, Eugene Morkin 1

1 University of Arizona

* Address correspondence to: E-mail: cadamson{at}u.arizona.edu

Abstract

The heart is an important target of thyroid hormone actions. Only a limited number of cardiac target genes have been identified and little is known about their regulation by T3 and thyroid hormone analogs. We used an oligonucleotide microarray to identify novel cardiac genes regulated by T3 and two thyroid hormone analogs, 3,5-diidodothyropropionic acid (DITPA) and CGS 23425. DITPA binds with lower affinity than T3 to thyroid hormone receptor {alpha}1 and {beta}1 isoforms whereas CGS 23425 binds selectively to {beta}1. Fluorescent-labeled cDNA was prepared from cultured heart cells maintained in medium stripped of thyroid hormone ('hypothyroid' control) or treated with T3, DITPA and CGS 23425 at concentrations 5X their respective Kd values for 48 h. The arrays were scanned and analyzed using an ANOVA program. Sixty-four genes were identified that were >1.5 times up or down regulated by one of the treatments with P<0.05. The genes regulated by T3 and DITPA were nearly identical. Thirteen genes were differentially regulated by CGS 23425. Genes encoding contractile proteins, Ca++-ATPase of sarcoplasmic reticulum and several proteins of mitochondrial oxidative phosphorylation were up regulated by T3 and DITPA but not by CGS 23425. These results indicate that the some, but not all of the actions of thyroid hormone analogs can be explained by differences in gene activation.


Key words: CGS 23425, Thyroid hormone, Thyroid hormone analogs, diiodothyropropionic acid, gene expression, microarray


This article has been cited by other articles:


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EndocrinologyHome page
S. A. Mousa, L. O'Connor, F. B. Davis, and P. J. Davis
Proangiogenesis Action of the Thyroid Hormone Analog 3,5-Diiodothyropropionic Acid (DITPA) Is Initiated at the Cell Surface and Is Integrin Mediated
Endocrinology, April 1, 2006; 147(4): 1602 - 1607.
[Abstract] [Full Text] [PDF]




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