Hormones, brain and stress
by
De Kloet RE.
Division of Medical Pharmacology, LACDR/LUMC,
Leiden University, 2300 RA Leiden,
The Netherlands.
e.kloet@lacdr.leidenuniv.nl
Endocr Regul. 2003 Jun;37(2):51-68


ABSTRACT

The stress system orchestrates body and brain responses to the environment. This action exerted by the mediators of the stress system has two modes of operation. The immediate response mode driven by corticotropin-releasing hormone (CRH) organises via CRH-1 receptors the behavioural, sympathetic and hypothalamic-pituitary-adrenal (HPA) responses to a stressor. In the other - slower - mode, which facilitates behavioural adaptation, the urocortins acting through CRH-2 receptors seem prominent. Corticosteroid hormones secreted by the adrenal cortex are implicated in both modes through their high affinity type 1 (mineralocorticoid receptors - MR) and lower affinity type 2 (glucocorticoid receptors - GR) receptors that are co-localised in limbic neural circuitry. Current data suggest that MR controls in specific afferents the threshold or sensitivity of the fast CRH-1 driven stress system mode and thus prevents disturbance of homeostasis, while GR facilitates its recovery by restraining in these very same circuits stress responses and by mobilising energy resources. In preparation for future events GR facilitates behavioural adaptation and promotes storage of energy. The balance in the two stress system modes is thought to be essential for cell homeostasis, mental performance and health. Imbalance induced by genetic modification or chronic stressors changes specific neural signalling pathways underlying psychic domains of cognition and emotion, anxiety and aggression. This Yin-Yang stress concept is fundamental for genomic strategies to understand the mechanistic underpinning of cortisol-induced stress-related disorders such as i.e. severe forms of depression and co-morbid diseases.
CRF
LHPA
Stress
Cytokines
Antalarmin
Ketoconazole
Noradrenaline
Corticosteroids
Making animals cry
Cushing's syndrome
New antidepressants
Glucocorticoids and mood
Hippocampal remodelling
Neuroendocrinology of stress
HPA axis, serotonin and suicide
Depression, opioids and the HPA
Antidepressants and new brain cells
The corticosteroid hypothesis of depression
Stress, dynorphin, dysphoria and the kappa opioid system


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