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Stress and disorders of the stress system

Abstract

All organisms must maintain a complex dynamic equilibrium, or homeostasis, which is constantly challenged by internal or external adverse forces termed stressors. Stress occurs when homeostasis is threatened or perceived to be so; homeostasis is re-established by various physiological and behavioral adaptive responses. Neuroendocrine hormones have major roles in the regulation of both basal homeostasis and responses to threats, and are involved in the pathogenesis of diseases characterized by dyshomeostasis or cacostasis. The stress response is mediated by the stress system, partly located in the central nervous system and partly in peripheral organs. The central, greatly interconnected effectors of this system include the hypothalamic hormones arginine vasopressin, corticotropin-releasing hormone and pro-opiomelanocortin-derived peptides, and the locus ceruleus and autonomic norepinephrine centers in the brainstem. Targets of these effectors include the executive and/or cognitive, reward and fear systems, the wake–sleep centers of the brain, the growth, reproductive and thyroid hormone axes, and the gastrointestinal, cardiorespiratory, metabolic, and immune systems. Optimal basal activity and responsiveness of the stress system is essential for a sense of well-being, successful performance of tasks, and appropriate social interactions. By contrast, excessive or inadequate basal activity and responsiveness of this system might impair development, growth and body composition, and lead to a host of behavioral and somatic pathological conditions.

Key Points

  • Stress occurs when homeostasis is threatened or perceived to be so

  • The stress response is mediated by the stress system, which is located in both the central nervous system and peripheral organs

  • The main central effectors of the stress system are highly interconnected, and include hypothalamic corticotropin-releasing hormone and brainstem-derived norepinephrine

  • Malfunction of the stress system is associated with behavioral and somatic disorders

  • Stress is a major contributor to psychosocial and physical pathological conditions in humans

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Figure 1: Homeostatic systems exert their effects in an inverse, U-type dose response.2
Figure 2: Chronic stress can lead to development of the metabolic syndrome.35

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Acknowledgements

This review is partially based on the Geoffrey Harris Memorial Lecture given by the author at the 10th European Congress of Endocrinology, 3–7 May 2008, Berlin, Germany.

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Chrousos, G. Stress and disorders of the stress system. Nat Rev Endocrinol 5, 374–381 (2009). https://doi.org/10.1038/nrendo.2009.106

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