title: Hormonal regulation of the human ghrelin receptor gene transcription.
abstract: The aim of this study is to clarify the hormonal regulation of the human ghrelin receptor gene expression in GH(3) cells transfected with our previously cloned 5'-flanking region inserted into a luciferase reporter vector. Phorbor 12-tetradecanoate 13-acetate (TPA) with simultaneous addition of Bay K8644 mimicking ghrelin action caused a significant inhibition of the luciferase activity through the ghrelin receptor gene upstream proximal to -669 but not to -608 base pairs (bp). Glucocorticoid caused a weak but significant inhibition of the luciferase activity through the ghrelin receptor gene upstream proximal to -531 but not to -475 bp. Electrophoretic mobility shift assay resulted in binding of oligonucleotides between -669 and -640 bp, and between -520 and -491 bp to GH(3) cell nuclear proteins unlike AP(2) or glucocorticoid receptor. These results suggest that both TPA/Bay K8644 and glucocorticoid downregulate human ghrelin receptor gene expression through the transcriptional mechanism involving some nuclear factors.
authors.affiliation: Department of Physiology and Biochemistry, College of Nursing Art and Science, Hyogo, Akashi 673-8588, Japan. kajis@hi-net.zaq.ne.jp
authors.forename: H
authors.initials: H
authors.lastname: Kaji
authors.forename: M
authors.initials: M
authors.lastname: Kishimoto
authors.forename: T
authors.initials: T
authors.lastname: Kirimura
authors.forename: G
authors.initials: G
authors.lastname: Iguchi
authors.forename: M
authors.initials: M
authors.lastname: Murata
authors.forename: S
authors.initials: S
authors.lastname: Yoshioka
authors.forename: K
authors.initials: K
authors.lastname: Iida
authors.forename: Y
authors.initials: Y
authors.lastname: Okimura
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshimoto
authors.forename: K
authors.initials: K
authors.lastname: Chihara
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D050882:CREB-Binding Protein; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D010902:Pituitary Gland / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D012045:Regulatory Sequences, Nucleic Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D015534:Trans-Activators; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004247:DNA; D008156:Luciferases; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone