Glucocorticoids, epigenetic control and stress resilience

Area of Science:

• Neuroendocrinology
• Stress Physiology
• Behavioral Science

Background:

• Glucocorticoid hormones are critical for managing stress responses.
• Dysregulated glucocorticoid secretion (hyper- or hypo-response) increases the risk for stress-related mental disorders.
• Maintaining optimal glucocorticoid function is essential for adaptation and resilience.

Purpose of the Study:

• To explore mechanisms controlling glucocorticoid function and stress resilience.
• To review the impact of lifestyle factors, specifically exercise, on stress response.
• To examine the role of genetic variations (SNPs) in glucocorticoid action and stress resilience.

Main Methods:

• Review of mechanisms controlling glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) function.
• Analysis of corticosteroid-binding globulin (CBG) in regulating free glucocorticoid availability.
• Examination of glucocorticoid signaling, epigenetic, and genomic effects on gene transcription.
• Review of studies on exercise interventions and their effects on the HPA axis, sleep, and behavior.
• Investigation into the role of the GABAergic system in exercise-mediated stress reduction.
• Discussion of single nucleotide polymorphisms (SNPs) impacting glucocorticoid action.

Main Results:

• Multiple complex mechanisms safeguard glucocorticoid function, including receptor control and hormone availability.
• Regular exercise positively impacts the HPA axis, sleep, cognition, and anxiety behaviors.
• Exercise may reduce stress impact via the GABAergic system in the dentate gyrus.
• Genetic variations (SNPs) in glucocorticoid action can impair stress resilience, particularly with childhood abuse.

Conclusions:

• Tight control of glucocorticoid secretion is fundamental for stress adaptation and resilience.
• Lifestyle choices, such as regular exercise, significantly influence stress resilience.
• Genetic factors interacting with environmental stressors (e.g., childhood abuse) can compromise glucocorticoid-mediated stress resilience.