Vol 8, No 4 - Stress
Past issues Contributors How to publish Contributions and comments Home
 
tress is commonly defined as a state of real or perceived threat to homeostasis.Maintenance of home- ostasis in the presence of aversive stimuli (stressors) requires activation of a complex range of responses involving the endocrine,nervous,and immune systems, collectively known as the stress response.1,2 Activation of the stress response initiates a number of behavioral and physiological changes that improve an individual’s chance of survival when faced with homeostatic chal- lenges.Behavioral effects of the stress response include increased awareness,improved cognition,euphoria,and enhanced analgesia.1,3 Physiological adaptations initiated by activation of this system include increased cardio- vascular tone,respiratory rate,and intermediate metab- olism,along with inhibition of general vegetative func- tions such as feeding,digestion,growth,reproduction, and immunity.4,5 Due to the wide array of physiologic and potentially pathogenic effects of the stress response, a number of neuronal and endocrine systems function to tightly regulate this adaptive process. Anatomy of the stress response The anatomical structures that mediate the stress response are found in both the central nervous system and peripheral tissues.The principal effectors of the stress response are localized in the paraventricular B a s i c  r e s e a r c h S Copyright © 2006 LLS SAS. All rights reserved www.dialogues-cns.org The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress Sean M.Smith,PhD;Wylie W.Vale,PhD Keywords:stress; corticotropin-releasing factor; adrenocorticotropic hormone; glucocorticoid; hypothalamus; pituitary gland; adrenal gland Author affiliations:Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, Calif, USA Address for correspondence:Wylie W. Vale, PhD, Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA (e-mail: vale@salk.edu) Animals respond to stress by activating a wide array of behavioral and physiological responses that are collec- tively referred to as the stress response. Corticotropin- releasing factor (CRF) plays a central role in the stress response by regulating the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, CRF initiates a cascade of events that culminate in the release of glucocorticoids from the adrenal cortex. As a result of the great number of physiological and behavioral effects exerted by gluco- corticoids, several mechanisms have evolved to control HPA axis activation and integrate the stress response. Glucocorticoid feedback inhibition plays a prominent role in regulating the magnitude and duration of glucocorti- coid release. In addition to glucocorticoid feedback, the HPA axis is regulated at the level of the hypothalamus by a diverse group of afferent projections from limbic, mid- brain, and brain stem nuclei. The stress response is also mediated in part by brain stem noradrenergic neurons, sympathetic andrenomedullary circuits, and parasympa- thetic systems. In summary, the aim of this review is to dis- cuss the role of the HPA axis in the integration of adap- tive responses to stress. We also identify and briefly describe the major neuronal and endocrine systems that contribute to the regulation of the HPA axis and the main- tenance of homeostasis in the face of aversive stimuli. © 2006, LLS SAS Dialogues Clin Neurosci. 2006;8:383-395.