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Stress and the General Adaptation Syndrome
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With the concept of the general adaptation syndrome we have attempted to integrate a number of seemingly quite unrelated observations into a single unified biologic system.I would draw attention briefly to the work of Claude Bernard, who showed how important it is to maintain the constancy of the "milieu interieur" ; Cannon's concept of " homoeostasis "; Frank Hartmann's " general tissue hor- mone" theory of the corticoids; Dustin's observations on the " caryoclastic poisons," the " post-operative disease," the curative action of fever, foreign proteins, and of other " non-specific therapeutic agents "; the " nephrotoxic sera " of Masugi; and to the " Goldblatt clamp" for the production of experimental renal hypertension.At first sight it would seem that all these observations have little in common and that there is no reason to attempt their integration into a unified system of physio- logical and pathological events.Yet most of my research work has been devoted to the construction of bridges between these and many additional facts, since they were thought to be interconnected in nature.Through the com- prehension of their unity we hoped to learn how to use them better for the understanding of life and the treatment of disease.The keynote of this unification was the tenet that all living organisms can respond to stress as such, and thiat in this respect the basic reaction pattern is always the same, irrespective of the agent used to produce stress.We called this response the general adaptation syndrome, and its derailments the diseases of adaptation.Anything that causes stress endangers life, unless it is met by adequate adaptive responses; conversely, anything that endangers life causes stress and adaptive responses.Adaptability and resistance to stress are fundamental pre- requisites for life, and every vital organ and function par- ticipates in them.In order to present a well-proportioned outline of the general adaptation syndrome it was necessary, therefore, to peruse every branch of physiology, biochemis- try, pathological anatomy, and clinical medicine in search of the "stress factor" in all aspects of normal and abnormal life.It will take many years, indeed many generations, before the details of the general adaptation syndrome are satis- *The first part of the Heberden Oration, given on June 2, 1950.
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“An updated version [10] of the classic general adaptation syndrome [152] and the foundational stress response theory of Horowitz [72], may provide a potential conceptual framework by postulating that stress reactions proceed through four hierarchical phases: freeze, flight, fight, and faint (or tonic immobility).”
From Complex PTSD and borderline personality disorder (2021) · cites this paper as [152]
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Logerstedt, D. S., Ebert, J. R., MacLeod, T. D., Heiderscheit, B. C., Gabbett, T. J., & Eckenrode, B. J. (2021) · Sports Medicine · doi:10.1007/s40279-021-01579-7 · Cited by 149
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Agathokleous, E., Belz, R. G., Calatayud, V., Marco, A. D., Hoshika, Y., Kitao, M., Saitanis, C. J., Sicard, P., Paoletti, E., & Calabrese, E. J. (2018) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2018.08.264 · Cited by 125
Light Pollution as a New Risk Factor for Human Breast and Prostate Cancers
Haim, A., & Portnov, B. A. (2013) · Springer eBooks · doi:10.1007/978-94-007-6220-6 · Cited by 133
Breslow, M. J. (1989) · JAMA · doi:10.1001/jama.1989.03420240091033 · Cited by 125
Modulatory effects of disease, stress, copper, TBT and vitamin E on the immune system of flatfish
Pulsford, A. L., Crampe, M., Langston, A., & Glynn, P. J. (1995) · Fish & Shellfish Immunology · doi:10.1016/s1050-4648(95)80046-8 · Cited by 124
A Framework for Periodized Nutrition for Athletics
Stellingwerff, T., Morton, J. P., & Burke, L. M. (2019) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.2018-0305 · Cited by 135
“Indeed, the seminal scientists and coaches who developed the principles of periodization include Dr. Hans Selye with his General Adaptation Syndrome model (Selye, 1950), followed by Matveyev, Bonderchuck, and Bompa (contributions reviewed by Issurin, 2010).”
BackgroundMethodGenetics of stress response and stress-related disorders
Ising, M., & Holsboer, F. (2006) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2006.8.4/mising · Cited by 118
Frank, M. G., Watkins, L. R., & Maier, S. F. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.01.005 · Cited by 116
“There has been tremendous interest in the effects of stress and GCs on inflammation since the pioneering reports by Selye (1950) that ‘‘stress’’ produces thymic involution and subsequent findings that ‘‘stress’’ seemed to suppress various aspects of immune function (Selye, 1955).”
BackgroundHeat Acclimation, Epigenetics, and Cytoprotection Memory
Horowitz, M. (2014) · Comprehensive physiology · doi:10.1002/cphy.c130025 · Cited by 134
“Notably, the universality of the mechanisms involved in the cellular stress response was already postulated by Selye (1950) (201) regarding the hypothalamo-pituitary-adrenal cortical axis, and stress hormones which are not discussed here.”
Extranuclear Steroid Receptors Are Essential for Steroid Hormone Actions
Levin, E. R. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-050913-021703 · Cited by 112
Siopi, E., Denizet, M., Gabellec, M.-M., de Chaumont, F., Olivo-Marin, J.-C., Guilloux, J.-P., Lledo, P.-M., & Lazarini, F. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2817-15.2016 · Cited by 111
“In conditions of chronic stress, when there is a sustained overproduction of glucocorticoids, this inhibitory feedback is impaired, creating a cascade of hippocampal damage and resulting in maladaptive stress responses (Selye, 1950; Mirescu and Gould, 2006).”
BackgroundDepression and physical illness: The prevalence, causation, and diagnosis of comorbidity
Schulberg, H. C., McClelland, M., & Burns, B. J. (1987) · Clinical Psychology Review · doi:10.1016/0272-7358(87)90031-6 · Cited by 111
Whole-Animal Physiological Processes for the Assessment of Stress in Fishes
Beitinger, T. L., & McCauley, R. W. (1990) · Journal of Great Lakes Research · doi:10.1016/s0380-1330(90)71445-1 · Cited by 110
Brooks, G. A., & Martin, N. A. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00408 · Cited by 107
“As part of the sympathetically mediated fight and flight mechanism (Selye, 1950; Selye and Fortier, 1950), both glycogen and glucose are precursors to glycolytic flux.”
BackgroundMunakata, M. (2018) · Hypertension Research · doi:10.1038/s41440-018-0053-1 · Cited by 106
Al-Ghareeb, A. Z., McKenna, L., & Cooper, S. J. (2019) · International Journal of Nursing Studies · doi:10.1016/j.ijnurstu.2019.06.006 · Cited by 105
Buwalda, B., Scholte, J. C. M., de Boer, S. F., Coppens, C. M., & Koolhaas, J. M. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.12.012 · Cited by 105
“With the concept of the general adaptation syndrome Hans Selye focused on the adaptive aspects of the bodily defense reactions, which he defined as stress, towards a wide variety of challenges to homeostasis (Selye, 1950).”
BackgroundZhao, Y., Bretz, C. A., Hawksworth, S. A., Hirsh, J., & Johnson, E. C. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009141 · Cited by 104
“Stress is defined as any challenge to the maintenance of homeostasis that produces adaptive behavioral and/or physiological responses [1].”
BackgroundInfluential
Metadata
- Authors
- Selye, H.
- Affiliations
- Université de Montréal (CA)
- Corresponding author
- Selye, H.
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 1950-06-17
- Volume
- 1
- Issue
- 4667
- Pages
- 1383-1392
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC2038162
- OpenAlex
- W1991680271
- Cited by
- 1,481
- References
- 0
- Citations by year
- 2026: 59 · 2025: 98 · 2024: 79 · 2023: 111 · 2022: 117 · 2021: 96 · 2020: 102 · 2019: 90 · 2018: 80 · 2017: 64 · 2016: 64 · 2015: 47 · 2014: 54 · 2013: 51 · 2012: 52
- FWCI
- 12.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- BMJ (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Bioactive Compounds
- Keywords
- general adaptation syndrome, stress, stress response, homeostasis, milieu intérieur, corticosteroids, tissue hormones, fever, nonspecific therapy, experimental renal hypertension, adaptability
- MeSH terms
- Acclimatization, Adaptation, Physiological, Adrenal Cortex, Adrenocorticotropic Hormone, General Adaptation Syndrome, Stress, Physiological, Tissue Extracts
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