Top-down and bottom-up control of stress-coping

Edo R. de Kloet*, Sybren F. de Kloet, Carien S. de Kloet, Annette D. de Kloet

*Corresponding author for this work

Research output: Contribution to JournalReview articleAcademicpeer-review


In this 30th anniversary issue review, we focus on the glucocorticoid modulation of limbic-prefrontocortical circuitry during stress-coping. This action of the stress hormone is mediated by mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) that are co-expressed abundantly in these higher brain regions. Via both receptor types, the glucocorticoids demonstrate, in various contexts, rapid nongenomic and slower genomic actions that coordinate consecutive stages of information processing. MR-mediated action optimises stress-coping, whereas, in a complementary fashion, the memory storage of the selected coping strategy is promoted via GR. We highlight the involvement of adipose tissue in the allocation of energy resources to central regulation of stress reactions, point to still poorly understood neuronal ensembles in the prefrontal cortex that underlie cognitive flexibility critical for effective coping, and evaluate the role of cortisol as a pleiotropic regulator in vulnerability to, and treatment of, trauma-related psychiatric disorders.

Original languageEnglish
Article numbere12675
Pages (from-to)1-16
Number of pages16
JournalJournal of Neuroendocrinology
Issue number3
Early online date22 Dec 2018
Publication statusPublished - Mar 2019

Bibliographical note

30th Anniversary Special Issue


  • adipose tissue
  • brain
  • cognitive flexibility
  • glucocorticoid receptors
  • limbic-prefrontocortical circuitry
  • mineralocorticoid receptors
  • PTSD

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