Glucocorticoid Secretion Under Stressful Conditions

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Living organisms survive by maintaining a complex dynamic equilibrium that is constantly challenged by intrinsic or extrinsic disturbing forces. In response to a stressor that exceeds a threshold magnitude, the organism changes its behavior and physiology to maintain homeostasis. Behavioral adaptation includes increased arousal and alertness, heightened attention, and suppression of feeding and sexual behavior. Concomitantly, physical adaptation occurs and includes functions that redirect energy sources to the stressed body site, where they are needed most. In this adaptive process, glucocorticoids, along with catecho-lamines, form the frontline of defense.

Glucocorticoid secretion during stress also is dependent upon the release of CRH and AVP, although the magnitude of PVN activity is influenced by the nature and intensity of the stressor. Simultaneously, the locus ceruleus/ norepinephrine-sympathetic system (autonomic-arousal system) becomes activated during stress, thus facilitating the release of epinephrine and norepinephrine from the adrenal medulla and the peripheral sympathetic nervous system. The PVN and the autonomic-arousal system are anatomically and functionally connected to each other and to the mesocortical/mesolimbic systems and the hippocampus.

Glucocorticoids and the Pathophysiology of Stress Response.

Generally, the stress response, with the resultant elevation of glucocorticoid levels, is meant to last only for a limited duration. The time-limited nature of this process renders its accompanying catabolic and immunosuppressive effects beneficial, with no adverse consequences. Chronic activation of the stress system, however, is detrimental. For example, prolonged exposure to elevated glucocorticoid levels results in suppression of anabolic processes, muscle atrophy, reduced sensitivity to insulin and a risk for diabetes, hypertension, hyperlipidemia, arterial disease, peptic ulcers, amenorrhea, impotence, immunosuppression, and the impairment of growth and tissue repair (Munck et al., 1984). In addition, elevated glucocorticoid levels are associated with psychopathology, neuronal damage, and impaired cognitive function (McEwen, 1994; Tsigos & Chrousos, 1994). An efficient endocrine response to stress is one that is rapidly mobilized in the presence of a threat and ef fectively terminated once the threatening condition is no longer present.

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