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

Neuron. 1994 Dec;13(6):1457-62. doi: 10.1016/0896-6273(94)90431-6.


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.

MeSH terms

  • Base Sequence
  • Cells, Cultured
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism*
  • Humans
  • In Vitro Techniques
  • Macromolecular Substances
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides / chemistry
  • Promoter Regions, Genetic*
  • Receptors, Glucocorticoid / physiology*
  • Receptors, Mineralocorticoid / physiology*
  • Transcription, Genetic
  • Transcriptional Activation


  • DNA-Binding Proteins
  • Macromolecular Substances
  • Oligodeoxyribonucleotides
  • Receptors, Glucocorticoid
  • Receptors, Mineralocorticoid
  • DNA