Thyrotropin-releasing hormone (TRH) and its mRNA have been identified in the rat 
heart, and TRH can enhance cardiomyocyte contractility in vivo. At present, 
little is known about cardiac TRH gene transcriptional regulation in the heart. 
Hormones and neurotransmitters, including thyroid hormone (T3), glucocorticoids, 
testosterone, and 5-HT initiate effects not only in the cardiovascular system, 
but also in the regulation of hypothalamic TRH. To clarify the potential roles 
of these modulators upon the cardiac TRH gene transcription, rat TRH promoter 
activity was assessed in rat embryonic myocyte cells (H9C2) by transient 
transfection assays. TRH promoter activity was stimulated significantly by 
dexamethasone (10(-4) M) and testosterone (10(-5) M), and was inhibited by T3 
(10(-7) M). Interestingly, the neurotransmitter 5-HT stimulated TRH promoter 
activity in H9C2 cells, but not in HTB-11 cells. To further clarify this 
selective role of 5-HT on TRH promoter transcriptional activity in cardiac 
cells, 5-HT receptor antagonists and agonists were tested. A selective 5-HT2 
receptor antagonist blocked 5-HT stimulation, whereas 5-HT agonist analogs 
caused augmentative effects when combined with 5-HT. Neither 5-HT nor any 
antagonists or agonists influenced H9C2 cell growth or morphology. These data 
suggest that 5-HT is an important transcriptional regulator of the cardiac TRH 
gene.