title: TTF-1 action on the transcriptional regulation of cyclooxygenase-2 gene in the rat brain.
abstract: We have recently found that thyroid transcription factor-1 (TTF-1), a homeodomain-containing transcription factor, is postnatally expressed in discrete areas of the hypothalamus and closely involved in neuroendocrine functions. We now report that transcription of cyclooxygenase-2 (COX-2), the rate limiting enzyme in prostaglandin biosynthesis, was inhibited by TTF-1. Double immunohistochemistry demonstrated that TTF-1 was expressed in the astrocytes and endothelial cells of blood vessel in the hypothalamus. Promoter assays and electrophoretic mobility shift assays showed that TTF-1 inhibited COX-2 transcription by binding to specific binding domains in the COX-2 promoter. Furthermore, blocking TTF-1 synthesis by intracerebroventricular injection of an antisense oligomer induced an increase of COX-2 synthesis in non-neuronal cells of the rat hypothalamus, and resulted in animals' hyperthermia. These results suggest that TTF-1 is physiologically involved in the control of thermogenesis by regulating COX-2 transcription in the brain.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Yun
authors.forename: Jae Geun
authors.initials: JG
authors.lastname: Kim
authors.forename: Byong Seo
authors.initials: BS
authors.lastname: Park
authors.forename: Hye Myeong
authors.initials: HM
authors.lastname: Lee
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Eun Ok
authors.initials: EO
authors.lastname: Kim
authors.forename: Joong Jean
authors.initials: JJ
authors.lastname: Park
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
authors.forename: Young Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D001665:Binding Sites; D001833:Body Temperature Regulation / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D047369:Chromatin Immunoprecipitation; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D059372:Nucleotide Motifs / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017384:Sequence Deletion / Q000235:genetics; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat