The glucocorticoid-mediated genomic stress response

In recent years, there has been a significant advance in our understanding about how stress-induced elevated glucocorticoid levels can modulate the transcription of target genes throughout the brain. In this way, glucocorticoids initiate a genomic stress response affecting physiological and cognitive processes, for example, associated with negative feedback mechanisms that underpin homeostasis, as well as coping behaviours, adaptation and consolidation of salient memories about the encountered stressor. The genomic action of glucocorticoids is mediated via two cognate receptors, the Type I and Type II corticosteroid receptors (MR and GR), which are both ligand-activated transcription factors. Recent advances include the characterisation of GR and MR homodimers, GR/MR heterodimers and higher-order oligomers, as well as new information about cell-type specific chromatin architecture and differential co-factor availability. Coupled with long-standing knowledge regarding their differing distrubution in the brain and different ligand-binding affinities, these recent advances help to explain the extraordinary functional range of this stress-responsive transcriptional regulatory system.