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The human stress response

Research output: Contribution to journalReview article

Original languageEnglish
Pages (from-to)525-534
Number of pages10
JournalNature Reviews Endocrinology
Volume15
Issue number9
Early online date27 Jun 2019
DOIs
DateAccepted/In press - 5 Jun 2019
DateE-pub ahead of print - 27 Jun 2019
DatePublished (current) - 1 Sep 2019

Abstract

The human stress response has evolved to maintain homeostasis under conditions of real or perceived stress. This objective is achieved through autoregulatory neural and hormonal systems in close association with central and peripheral clocks. The hypothalamic-pituitary-adrenal axis is a key regulatory pathway in the maintenance of these homeostatic processes. The end product of this pathway - cortisol - is secreted in a pulsatile pattern, with changes in pulse amplitude creating a circadian pattern. During acute stress, cortisol levels rise and pulsatility is maintained. Although the initial rise in cortisol follows a large surge in adrenocorticotropic hormone levels, if long-term inflammatory stress occurs, adrenocorticotropic hormone levels return to near basal levels while cortisol levels remain raised as a result of increased adrenal sensitivity. In chronic stress, hypothalamic activation of the pituitary changes from corticotropin-releasing hormone-dominant to arginine vasopressin-dominant, and cortisol levels remain raised due at least in part to decreased cortisol metabolism. Acute elevations in cortisol levels are beneficial to promoting survival of the fittest as part of the fight-or-flight response. However, chronic exposure to stress results in reversal of the beneficial effects, with long-term cortisol exposure becoming maladaptive, which can lead to a broad range of problems including the metabolic syndrome, obesity, cancer, mental health disorders, cardiovascular disease and increased susceptibility to infections. Neuroimmunoendocrine modulation in disease states and glucocorticoid-based therapeutics are also discussed.

    Research areas

  • Adrenal cortex hormones, Stress signalling, Multihormonal system disorders, Circadian rhythms

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Springer Nature at https://www.nature.com/articles/s41574-019-0228-0#. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 294 KB, PDF document

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