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Am J Physiol Heart Circ Physiol (February 27, 2003). doi:10.1152/ajpheart.00860.2002
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Submitted on October 3, 2002
Accepted on February 17, 2003

TRIIODOTHYRONINE-MEDIATED MYOSIN HEAVY CHAIN GENE TRANSCRIPTION IN THE HEART

Sara Danzi1*, Kaie Ojamaa2, and Irwin Klein2

1 Division of Endocrinology and Department of Medicine, North Shore University Hospital, Manhasset, NY, USA
2 Division of Endocrinology and Department of Medicine, North Shore University Hospital, Manhasset, NY, USA; Department of Cell Biology, NYU School of Medicine, New York, NY, USA

* To whom correspondence should be addressed. E-mail: sdanzi{at}nshs.edu.

We developed an RT PCR assay to study both the time course and the mechanism for the T3-induced transcription of the {alpha}- and {beta}-MHC (myosin heavy chain) genes in vivo based on 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/100g body weight). Maximal transcription rates (135%±15.8 of euthyroid values) occurred 6 hours 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 hours after a single T3 injection and reached a nadir of 59% of hypothyroid levels at 36 hours. Analysis of the time course of T3-mediated induction of {alpha}-MHC hnRNA and repression of {beta}-MHC hnRNA indicate that separate molecular mechanisms are involved in the coordinated regulation of these genes.




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