This overview has explored the pathophysiological consequences of an evoked, excessive perturbation of one of the principal axes of neuroendocrine response in the human body. In the following section, the environmental factors that influence the HPA axis will be reviewed.
A common, powerful group of activators are those included under the concept of stress. The origin of the concept of stress in biology and medicine is unknown. Investigations of stress rise from the recognition by Claude Bernard in 1878 that all living processes exist in a 'milieu interieur', formed by organic liquid that surrounds all of the tissue elements. Cannon elucidated the mechanisms of maintaining physiological factors within certain limits and coined the term 'homeostasis' and defined it as 'the coordinated physiological process which maintains most of the steady states in the organisms' (92). He describes a 'critical stress' level that produces a 'breaking strain' that results in failure to maintain homeostasis, and he adopts the terms 'stress' and 'strain' as they are used in physics. Selye extended Cannon's concept of homeostasis to include the responses mediated by the HPA axis and proposed a new concept of stress, 'general adaptation syndrome, or GAS'; a single stereotypic response elicited by any demand upon the body (93). For scientific purpose, he defined stress 'as the state which manifests itself by the GAS'.
As the homeostasis is constantly threatened by internal or external adverse factors, stressors, stress is usually defined as a state of threatened homeo-stasis (17). There are physical stressors such as cold, trauma, fever and infection; psychological stressors such as social subordination, anxiety and depression (94).
Traits of anxiety and depression have a predictive association with visceral obesity in both men and women (55,56). Furthermore, alcohol consumption and smoking are common among subjects with elevated WHR (51,52). In addition, we have recently identified a number of psychosocial and socioeconomic handicaps in this condition (51,52). The most prominent factors are divorce, solitude, poor economy and low education, unemployment, and problems at work when employed. Interestingly, socioeconomic inequality and low educational have recently been shown to be associated with elevated stress-related cortisol secretion as well as visceral obesity (95). Moreover, we have identified a subgroup of elevated WHR and D, where a blunted dexamethasone response is found, associated with traits of anxiety and depression as well as personality disorders (57,96).
It has been suggested that persistent psychosocial and socioeconomic handicaps constitute a base for stress, resulting in frequent challenges of the HPA axis (43). Although biologically plausible, this hypothesis has been difficult to study in humans. In primates other than humans, a diminished feedback regulation of the cortisol secretion, suppression of the reproductive axis, and depressive behaviour follow exposure to standardized, moderate psychosocial stress (97,98). Moreover, such social stress is associated with visceral obesity, insulin resistance, dyslipidaemia, hypertension and coronary artery atherosclerosis (97,98). Thus, these results bear a striking resemblance to that of humans subjected to psychosocial stress, followed by visceral obesity with metabolic syndrome. These studies then provide a solid experimental groundwork for the hypothesis that psychosocial stress and socioeconomic subordination is indeed inducing the metabolic syndrome.
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