title: Serotonin (5-HT) stimulates thyrotropin-releasing hormone (TRH) gene transcription in rat embryonic cardiomyocytes.
abstract: 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.
authors.affiliation: Department of Medicine, University of Maryland, School of Medicine at Baltimore 21201, USA. zshi@umabnet.ab.umd.edu
authors.forename: Z X
authors.initials: ZX
authors.lastname: Shi
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.forename: M K
authors.initials: MK
authors.lastname: Selmanoff
authors.forename: J F
authors.initials: JF
authors.lastname: Wilber
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D005938:Glucocorticoids; D014284:Triiodothyronine; D012701:Serotonin; D013973:Thyrotropin-Releasing Hormone; D003907:Dexamethasone