Cited by 3,083Stress Responses and CortisolAdrenal Hormones and DisordersEstrogen and related hormone effects

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Physiological functions of glucocorticoids in stress and their relation to pharmacological actions

MUNCK, ALLAN, GUYRE, PAUL M., HOLBROOK, NIKKI J.·1984·Endocrine Reviews

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Abstract

Almost any kind of threat to homeostasis or stress will cause plasma glucocorticoid levels to rise. The increased levels have traditionally been ascribed the physiological function of enhancing the organism's resistance to stress, a role well recognized in glucocorticoid therapy. How the known physiological and pharmacological effects of glucocorticoids might accomplish this function, however, remains a mystery. A generalization that is beginning to emerge is that many of these effects may be secondary to modulation by glucocorticoids of the actions of numerous intercellular mediators, including established hormones, prostaglandins and other arachidonic acid metabolites, certain secreted neutral proteinases, lymphokines, and a variety of bioactive peptides. These mediators participate in physiological mechanisms--endocrine, renal, immune, neural, etc.--that mount a first line of defense against such challenges to homeostasis as hemorrhage, metabolic disturbances, infection, anxiety, and others. Contrary to the traditional view that glucocorticoids enhance these defense mechanisms, however, it has become increasingly clear that glucocorticoids at moderate to high levels generally suppress them. This paradox, which first emerged when glucocorticoids were discovered to be antiinflammatory agents, remains a major obstacle to a unified picture of glucocorticoid function. We propose that stress-induced increases in glucocorticoid levels protect not against the source of stress itself but rather against the body's normal reactions to stress, preventing those reactions from overshooting and themselves threatening homeostasis. This hypothesis, the seeds of which are to be found in many discussions of particular glucocorticoid effects, immediately accounts for the paradox noted above. Furthermore, it provides glucocorticoid physiology with a unified conceptual framework that can accommodate such apparently unrelated physiological and pharmacological effects as those on carbohydrate metabolism, inflammatory processes, shock, and water balance. It also leads us to suggest that some of the enzymes rapidly induced by glucocorticoids, such as glutamine synthetase, detoxify mediators released during stress-induced activation of primary defense mechanisms. These mediators would themselves lead to tissue damage if left unchecked.

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Authors: MUNCK, A., GUYRE, P. M., & HOLBROOK, N. J.
Affiliations: Dartmouth College (US)
Venue: Endocrine Reviews
Publisher: The Endocrine Society
Published: 1984-01
Volume: 5
Issue: 1
Pages: 25-44
ISSN: 0163-769X (ISSN-L)
1945-7189
DOI: 10.1210/edrv-5-1-25
OpenAlex: W2068392981
Cited by: 3,083
References: 72
Citations by year: 2026: 19 · 2025: 33 · 2024: 36 · 2023: 40 · 2022: 47 · 2021: 51 · 2020: 58 · 2019: 54 · 2018: 57 · 2017: 71 · 2016: 58 · 2015: 60 · 2014: 58 · 2013: 66 · 2012: 68
FWCI: 17.94
Type: journal article
Language: en
Open access: closed
Locations: Endocrine Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Keywords: glucocorticoids, stress response, homeostasis, anti-inflammatory activity, glutamine synthetase, prostaglandins, arachidonic acid metabolites, lymphokines, neutral protease, immunosuppression, carbohydrate metabolism, shock, water balance, tissue damage
MeSH terms: Animals, Anti-Inflammatory Agents, Body Water, General Adaptation Syndrome, Glucocorticoids, Hormones, Humans, Immunosuppressive Agents, Interleukin-1, Interleukin-2, Lymphokines, Models, Biological, Shock, Stress, Physiological, Carbohydrate Metabolism

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Physiological functions of glucocorticoids in stress and their relation to pharmacological actions

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