Positive and negative regulation of the rat vasopressin gene promoter

Endocrinology. 1997 Dec;138(12):5266-74. doi: 10.1210/endo.138.12.5639.


To study the transcriptional regulation of the vasopressin gene in vitro, 3 kb of the 5' regulatory region of the rat vasopressin gene was isolated and subcloned, along with a series of various deletion mutants, into vectors containing the luciferase reporter gene. After transfecting these genes transiently into the human choriocarcinoma cell line JEG-3 along with a glucocorticoid receptor (GR) expression vector, transcriptional activity was quantitated using the luciferase assay. Forskolin, 8-bromo-cAMP, and protein kinase A catalytic subunit expression all markedly increased transcription from the 3-kb promoter. Analyses with deletion mutants of the promoter showed that two cAMP-responsive element (CRE)-like sequences (-227 to -220 bp and -123 to -116 bp) contribute to this positive regulation. Expression of KCREB, a dominant negative mutant of the cAMP-responsive element binding protein (CREB), suggested the involvement of CREB. Transfection of the activator protein 2 (AP2) DNA consensus sequence partially blocked transcription. Dexamethasone suppressed forskolin-stimulated expression. The negative effect of glucocorticoid was GR dependent and may be mediated by a mechanism not involving GR binding to DNA because it was independent of the putative glucocorticoid-responsive element previously reported in the vasopressin promoter (-622 to -608 bp) and was preserved in the shorter promoter constructs in which no glucocorticoid-responsive element-like sequence was found. Our data suggest that several trans-acting factors including CREB, AP2, and GR are likely to be involved in vasopressin gene transcription and that the positive and negative regulation of vasopressin gene transcription is complex.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Colforsin / pharmacology
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dexamethasone / pharmacology
  • Gene Deletion
  • Gene Expression Regulation / physiology
  • Glucocorticoids / pharmacology
  • Humans
  • Molecular Sequence Data
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / physiology*
  • Protein Kinase C / metabolism
  • Rats
  • Tumor Cells, Cultured
  • Vasopressins / genetics*


  • Cyclic AMP Response Element-Binding Protein
  • Glucocorticoids
  • Vasopressins
  • Colforsin
  • Dexamethasone
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C