Triiodothyronine-mediated myosin heavy chain gene transcription in the heart

Abstract

We developed an RT-PCR assay to study both the time course and the mechanism for the triiodothyronine (T3)-induced transcription of the α- and β-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 α-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 α-MHC hnRNA demonstrated that T3 induced α-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 β-MHC was reduced to 86% of peak hypothyroid levels 6 h after a single T3injection and reached a nadir of 59% of hypothyroid levels at 36 h. Analysis of the time course of T3-mediated induction of α-MHC hnRNA and repression of β-MHC hnRNA indicates that separate molecular mechanisms are involved in the coordinated regulation of these genes.