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Am J Physiol Heart Circ Physiol 284: H2255-H2262, 2003. First published February 27, 2003; doi:10.1152/ajpheart.00860.2002
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Vol. 284, Issue 6, H2255-H2262, June 2003

Triiodothyronine-mediated myosin heavy chain gene transcription in the heart

Sara Danzi, Kaie Ojamaa, and Irwin Klein

Division of Endocrinology and Department of Medicine, North Shore University Hospital/New York University School of Medicine, Manhasset 11030; and Department of Cell Biology, New York University School of Medicine, New York, New York 10021

We developed an RT-PCR assay to study both the time course and the mechanism for the triiodothyronine (T3)-induced transcription of the alpha - and beta -myosin heavy chain (MHC) genes in vivo on the basis of the quantity of specific heterogeneous nuclear RNA (hnRNA). The temporal relationship of changes in transcriptional activity to the amount of alpha -MHC mRNA and the coordinated regulation of transcription of more than one gene in response to T3 are demonstrated here for the first time. Quantitation of alpha -MHC hnRNA demonstrated that T3 induced alpha -MHC transcription in hypothyroid rats within 30 min of a single injection of T3 (0.5 µg/100 g body wt). Maximal transcription rates (135% ± 15.8 of euthyroid values) occurred 6 h after injection and subsequently declined in parallel with serum T3 levels. The transcription of beta -MHC was reduced to 86% of peak hypothyroid levels 6 h after a single T3 injection and reached a nadir of 59% of hypothyroid levels at 36 h. Analysis of the time course of T3-mediated induction of alpha -MHC hnRNA and repression of beta -MHC hnRNA indicates that separate molecular mechanisms are involved in the coordinated regulation of these genes.

cardiac contractility; heterogeneous nuclear ribonucleic acid; thyroid hormone; thyroid disease


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