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 T(3) (3,3',5-triiodothyronine) and thyroid hormone analogs. 
We used an oligonucleotide microarray to identify novel cardiac genes regulated 
by T(3) and two thyroid hormone analogs, 3,5-diidodothyropropionic acid (DITPA) 
and CGS 23425 [N-[3,5-dimethyl-4-(4'-hydroxy-3'-isopropylphenoxy)-phenyl]-oxamic 
acid]. DITPA binds with lower affinity than T(3) to thyroid hormone receptor 
alpha1 and beta1 isoforms, whereas CGS 23425 binds selectively to beta1. 
Fluorescent-labeled cDNA was prepared from cultured heart cells maintained in 
medium stripped of thyroid hormone ("hypothyroid" control) or treated with T(3), 
DITPA, and CGS 23425 at concentrations 5 times their respective K(d) values for 
48 h. The arrays were scanned and analyzed using an analysis of variance 
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 
T(3) and DITPA were nearly identical. Thirteen genes were differentially 
regulated by CGS 23425. Genes encoding contractile proteins, Ca(2+)-ATPase of 
sarcoplasmic reticulum and several proteins of mitochondrial oxidative 
phosphorylation, were up-regulated by T(3) and DITPA but not by CGS 23425. These 
results indicate that some, but not all, of the actions of thyroid hormone 
analogs can be explained by differences in gene activation.