Protective and Damaging Effects of Stress Mediators

Abstract

VER 60 years ago, Selye 1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly contradictory roles? How does stress influence the pathogenesis of disease, and what accounts for the variation in vulnerability to stress-related diseases among people with similar life experiences? How can stress-induced damage be quantified? These and many other questions still challenge investigators.This article reviews the long-term effect of the physiologic response to stress, which I refer to as allostatic load. 2 Allostasis -the ability to achieve stability through change 3 -is critical to survival. Through allostasis, the autonomic nervous system, the hypothalamic-pituitary-adrenal (HPA) axis, and the cardiovascular, metabolic, and immune systems protect the body by responding to internal and external stress. The price of this accommodation to stress can be allostatic load, 2 which is the wear and tear that results from chronic overactivity or underactivity of allostatic systems.

Basal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and psychological distress in recreational ecstasy polydrug users

“…This finding is analogous to previous observations of elevated cortisol immediately prior to a laboratory stressor (Gerra et al, 2003) and suggests that users may have a greater negative perception of the forthcoming challenge (Gerra et al, 1998). Although activation of cortisol in anticipation of and in response to stress is adaptive, allowing the host to mobilise the resources necessary to deal with threat, excessive or inappropriate responding increases allostatic load (McEwen 1998) and the risk of deleterious consequences for ill-health.…”

Social stress shortens lifespan in mice

“…Our results find support in results showing how the impact of stress on cardiovascular and psychiatric diseases is modulated by a passive or reactive coping style in response to stressful situations (Koolhaas et al., 1999). Consistently, subordinate male mice, corresponding to subjects characterized by high aggression received and low aggression exhibited, manifested HPA axis upregulation that is one of the common markers of chronic stress and allostatic load (McEwen, 1998; Seeman et al., 1997), which might set the stage for metabolic disease thus compromising healthspan. Subordinate mice also showed transient hyperglycemia and lifelong hyperphagia.…”

Prolactin, testosterone and cortisol as possible markers of changes in cardiovascular function associated with urbanization

“…This gives rise to the idea that the subjects in stratum 3 also experience stress, but not to such an extent that their testosterone secretion is diminished and their cortisol secretion is suppressed by negative feedback control mechanisms. 22,26 A possibility is that the activation of the adrenomedullary hormonal system may be involved in the testosterone levels, which is lower than what can be expected, in the defence (or in control of the situation) mode. 35 It is more likely however that this is an indication of a defeat or submissive reactivity pattern because of the high levels of prolactin and the absence of a rise in testosterone as well as the high level of cortisol in comparison with stratum 5.…”

“…Both hypercortisolism and hypocortisolism have been described as a stress response and can be modified by environmental social factors and gender. 22,25,26 According to Heim et al 22 and Hellhammer and Wade, 25 hypercortisolism is associated with the initial phase of stress, dominance in society and male gender and hypocortisolism is associated with chronic stress, lower social position and female gender. Although these associations must be handled with caution, the ongoing stress of the harsh living conditions in an informal settlement may lead to a decrease of cortisol levels.…”