title: Increased glucocorticoid receptor gene promoter activity after antidepressant treatment.
abstract: We have tested the hypothesis that antidepressants affect the expression of the glucocorticoid receptor gene, by looking at glucocorticoid receptor gene promoter activity, glucocorticoid receptor mRNA levels, and glucocorticoid-binding activity after treatment of different cell lines with desipramine. Treatment of LTK- cells or Neuro 2A cells with desipramine produced a 50-200% increase in chloramphenicol acetyltransferase activity transcribed from a 2.7-kilobase glucocorticoid receptor gene promoter region. In cell lines derived from both neuronal and non-neuronal sources, glucocorticoid receptor mRNA concentration doubled after desipramine treatment, and this was associated with a 2-fold higher functional glucocorticoid binding capacity and increased glucocorticoid sensitivity, as measured with the reporter plasmid pMMTVCAT. Antidepressant-induced increases in glucocorticoid receptor gene promoter activity, glucocorticoid receptor mRNA levels, and functional glucocorticoid binding activity suggest a novel mechanism of action for these drugs on the hypothalamic-pituitary-adrenal axis.
authors.affiliation: Molecular Psychogenetics Laboratory, Research Center, Ste Foy, Québec, Canada.
authors.forename: M C
authors.initials: MC
authors.lastname: Pepin
authors.forename: M V
authors.initials: MV
authors.lastname: Govindan
authors.forename: N
authors.initials: N
authors.lastname: Barden
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D002678:Chimera / Q000235:genetics; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003891:Desipramine / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: D000928:Antidepressive Agents; D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D015500:Chloramphenicol O-Acetyltransferase; D003891:Desipramine