title: Role of glucocorticoid hormones in arginine vasopressin gene regulation.
abstract: The mechanism underlying increased AVP synthesis and release in glucocorticoid deficiency is not known. Therefore, the present study was undertaken to investigate whether the mechanism was at the level of AVP gene transcription. The AVP gene promoter contains a consensus GRE, a CRE, and four AP2 sites. To assess the functional importance of these sites, 5' deletions of the AVP promoter were created and transient transfections were performed. Promoter activity in hypothalamic cells transfected with deletions lacking the GRE or both the GRE and CRE exhibited higher activity when compared to longer constructs containing both sites. In neuroblastoma cells, only the deletion lacking the GRE exhibited increased AVP promoter activity over the longer construct. These results are consistent with the idea that glucocorticoids suppress AVP gene expression by acting on a GRE in the AVP promoter region. Further, dexamethasone inhibited AVP promoter activity by >50% in hypothalamic cells transfected with the GRE-containing construct. In conclusion, the data presented here support a central mechanism to explain, at least in part, the nonosmotic increase in AVP with glucocorticoid deficiency.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Kim
authors.forename: S N
authors.initials: SN
authors.lastname: Summer
authors.forename: W M
authors.initials: WM
authors.lastname: Wood
authors.forename: R W
authors.initials: RW
authors.lastname: Schrier
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017384:Sequence Deletion; D014162:Transfection; D015854:Up-Regulation
chemical_list: D005938:Glucocorticoids; D001127:Arginine Vasopressin; D003907:Dexamethasone; D004247:DNA