Stress, Glucocorticoids, and the Brain

  • R. H. DeRijk
  • E. R. de Kloet
Part of the Nutrition and Health book series (NH)


When deviations in physiological or behavioral parameters exceed a certain threshold, central release of corticotropin-releasing hormone (CRH) from the parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) is triggered. CRH activates, in the specific context of the stressor, the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, which promote a series of physiological and behavioral adaptations in order to reestablish homeostasis (McEwen, 1998). Multiple afferents can activate CRH neurons, each conveying specific stressful information. These afferents can be ascending direct innervations from the brainstem that relay stressors of systemic origin (metabolic demands, fluid loss, pain, inflammation). Sensory cognitive and emotional information also reaches via a complex transsynaptic pathway—the PVN (Herman et al., 2003). The summation of all inputs to the PVN provides an output that can be measured as the threshold for activation of these neurons as well as the rate of onset, magnitude and duration of the response. The type of afferent input additionally determines the composition of the cocktail of adrenocorticotropic hormone (ACTH) secretagogs released with CRH in interaction with other stress hormones (e.g., norepinephrine [NE] and epinephrine [E]) (Goldstein, 2003; Herman et al., 2003; Romero & Sapolsky, 1996). This initial CRH-mediated stress reaction is counterbalanced by the stress-induced elevation in circulating levels of glucocorticoids and by parasympathetic nervous system activity. Recently it has been suggested that the CRH-2 receptor system is prominent in the coordination of these later slow responses, facilitating the recovery of homeostasis (Hsu & Hsueh, 2001; Reul & Holsboer, 2002).


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Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • R. H. DeRijk
    • 1
  • E. R. de Kloet
    • 1
  1. 1.Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug ResearchLeiden UniversityLeidenThe Netherlands

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