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Hormones, brain and stress.

E Ronald de Kloet1

  • 1Division of Medical Pharmacology, LACDR/LUMC, Leiden University, 2300 RA Leiden, The Netherlands. e.kloet@lacdr.leidenuniv.nl

Endocrine Regulations
|August 23, 2003
PubMed
Summary

The stress system has two modes: immediate (CRH-1) and adaptive (CRH-2). Mineralocorticoid receptors (MR) manage sensitivity, while glucocorticoid receptors (GR) aid recovery and energy storage for balanced health.

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Area of Science:

  • Neuroendocrinology
  • Stress Physiology
  • Behavioral Neuroscience

Background:

  • The stress system regulates body and brain responses to environmental challenges.
  • It operates in two distinct modes: immediate and adaptive.
  • Mediators include corticotropin-releasing hormone (CRH) and corticosteroid hormones.

Purpose of the Study:

  • To elucidate the distinct roles of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) in stress response modulation.
  • To explain the 'Yin-Yang' balance between immediate and adaptive stress responses.
  • To highlight the implications of stress system imbalance for health and disease.

Main Methods:

  • Review and synthesis of existing data on stress system mediators and receptors.
  • Analysis of the functional interplay between CRH-1, CRH-2, MR, and GR.
  • Examination of the impact of genetic and chronic stress on neural pathways.

Main Results:

  • The immediate stress response is mediated by CRH acting on CRH-1 receptors, with MR regulating its sensitivity.
  • The slower, adaptive response involves urocortins acting on CRH-2 receptors, with GR facilitating recovery and energy storage.
  • GR and MR co-localize in limbic circuitry, influencing stress response thresholds and recovery.

Conclusions:

  • A balanced interplay between MR and GR is crucial for maintaining homeostasis, cognitive function, and overall health.
  • Imbalances in the stress system can lead to altered neural signaling, impacting emotion, cognition, anxiety, and aggression.
  • Understanding this stress system balance is fundamental for developing genomic strategies for stress-related disorders like depression.

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