Stress and corticosteroid receptors

Abstract

The hypothalamo-pituitary-adrenal (HPA) axis is the main hormonal system involvedin stress response. Neurons in the hypothalamic paraventricular nucleus secreteadrenocorticotrophic hormone-releasing hormone (CRF) and vasopressin,which then synergistically induce the secretion of adrenocorticotrophic hormone(ACTH) from corticotrophs in the anterior pituitary, activating the secretion of theglucocorticoids from the adrenal cortex. Glucocorticoids (Cortisol in human andcorticosterone in rodents) readily enter the brain from the circulating blood andbind to their receptors to induce the secretion of CRF and ACTH for feedback regulationto keep homeostasis through the HPA axis. Over the past decades there hasbeen increasing evidence supporting a critical role for the hippocampus in stressresponse (McEwen 1999). Neurons in the hippocampus express receptors for circulatingglucocorticoids, and animal models of repeated stress caused dendritic atrophyin CAS pyramidal neurons (Woolley et al. 1990; Watanabe et al. 1992; Magarinosand McEwen 1995; Sousa et al. 2000). In the primate prominent pyramidalneuron examples of damage such as dendritic atrophy and pyknotic changes wereobserved in the CAS area of animals subjected to repeated social stress and longtermtreatment of Cortisol (Uno et al. 1989, Sapolsky et al. 1990). These results suggestthat dendritic atrophy of the pyramidal neurons may be one of the factors contributingto the clinically observed decrease of hippocampal volume in humans sufferingfrom stress-related disorders including the posttraumatic stress disorder(PTSD) (Bremner et al. 1995). Transsynaptic inhibitory projection of the hippocampusto hypothalamic paraventricular nucleus has been demonstrated. Therefore, thehippocampus has been the focus of the stress response not only due to its susceptibilityto stress-related damages but also to its negative feedback regulation of thestress response via the HPA axis (Herman and Cullinan 1997). In contrast to thehippocampus, little has been known about how stress affects the amygdala and thenature of its role in the stress response. Recent evidence has demonstrated that theamygdala also plays a critical role in stress response and activation of the HPA axis(Le Doux 1994). It has been suggested that hippocampal plasticity mediates cogni-tive aspects of behavioral impairments caused by stress, whereas changes in theamygdala are more likely to contribute to the affective aspects of stress disorderswith memory consolidation.