Heterodimerization between mineralocorticoid and glucocorticoid receptor: a new principle of glucocorticoid action in the CNS

T Trapp, R Rupprecht, M Castrén, J M Reul, F Holsboer

Research output: Contribution to journalArticle (Academic Journal)peer-review

247 Citations (Scopus)

Abstract

In the mammalian central nervous system, responsiveness to glucocorticoids is mediated by both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). These pharmacologically distinct receptors are believed to bind to common response elements as homodimers. We provide evidence that MR and GR can form a heterodimeric complex with DNA-binding and transactivation properties different from those of the respective homodimers. There was a high degree of cooperativity of MR and GR in binding to a glucocorticoid response element. Transient transfection of a neuroblastoma cell line revealed a transcriptional response pattern of coexpressed MR and GR distinct from that obtained by MR or GR alone. Our findings demonstrate that heterodimerization of MR and GR is a hitherto unrecognized principle for the transcriptional regulation of glucocorticoid-responsive genes in tissue coexpressing these receptors.

Original languageEnglish
Pages (from-to)1457-62
Number of pages6
JournalNeuron
Volume13
Issue number6
Publication statusPublished - Dec 1994

Keywords

  • Base Sequence
  • Cells, Cultured
  • DNA
  • DNA-Binding Proteins
  • Humans
  • Macromolecular Substances
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Promoter Regions, Genetic
  • Receptors, Glucocorticoid
  • Receptors, Mineralocorticoid
  • Transcription, Genetic
  • Transcriptional Activation

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