Stressor specificity of central neuroendocrine responses: implications for stress-related disorders

Pacák, Karel; Palkovits, Miklós

doi:10.1210/edrv.22.4.0436

Cited by 926Stress Responses and CortisolNeuropeptides and Animal PhysiologyAdrenal Hormones and Disorders

Stressor specificity of central neuroendocrine responses: implications for stress-related disorders

Pacák, Karel, Palkovits, Miklós·2001·Endocrine Reviews

DOI 10.1210/edrv.22.4.0436

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Abstract

Despite the fact that many research articles have been written about stress and stress-related diseases, no scientifically accepted definition of stress exists. Selye introduced and popularized stress as a medical and scientific idea. He did not deny the existence of stressor-specific response patterns; however, he emphasized that such responses did not constitute stress, only the shared nonspecific component. In this review we focus mainly on the similarities and differences between the neuroendocrine responses (especially the sympathoadrenal and the sympathoneuronal systems and the hypothalamo-pituitary-adrenocortical axis) among various stressors and a strategy for testing Selye's doctrine of nonspecificity. In our experiments, we used five different stressors: immobilization, hemorrhage, cold exposure, pain, or hypoglycemia. With the exception of immobilization stress, these stressors also differed in their intensities. Our results showed marked heterogeneity of neuroendocrine responses to various stressors and that each stressor has a neurochemical "signature." By examining changes of Fos immunoreactivity in various brain regions upon exposure to different stressors, we also attempted to map central stressor-specific neuroendocrine pathways. We believe the existence of stressor-specific pathways and circuits is a clear step forward in the study of the pathogenesis of stress-related disorders and their proper treatment. Finally, we define stress as a state of threatened homeostasis (physical or perceived treat to homeostasis). During stress, an adaptive compensatory specific response of the organism is activated to sustain homeostasis. The adaptive response reflects the activation of specific central circuits and is genetically and constitutionally programmed and constantly modulated by environmental factors.

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The PVN is innervated by GABAergic AHA neurons implicated in glucocorticoid-induced negative feedback regulation of HPA axis function.
“The PVN is innervated by GABAergic AHA neurons implicated in glucocorticoid-induced negative feedback regulation of HPA axis function (Pacak and Palkovits, 2001; Herman et al., 2002).”
From Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit (2014) · cites this paper as Pacak and Palkovits, 2001

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Authors: Pacák, K., & Palkovits, M.
Affiliations: Pediatric and Reproductive Endocrinology Branch (K.P.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
Laboratory of Genetics (M.P.), National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1583
Venue: Endocrine Reviews
Publisher: The Endocrine Society
Published: 2001-08-01
Volume: 22
Issue: 4
Pages: 502-548
ISSN: 0163-769X (ISSN-L)
1945-7189
DOI: 10.1210/edrv.22.4.0436
OpenAlex: W2066156347
Cited by: 926
References: 486
Citations by year: 2026: 15 · 2025: 18 · 2024: 21 · 2023: 24 · 2022: 23 · 2021: 26 · 2020: 28 · 2019: 24 · 2018: 38 · 2017: 27 · 2016: 36 · 2015: 47 · 2014: 45 · 2013: 39 · 2012: 56
FWCI: 4.07
Type: journal article
Language: en
Open access: closed
Locations: Endocrine Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Child Health and Human Development
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords: stressor specificity, neuroendocrine response, stress-related disorders, sympathoadrenal system, hypothalamic-pituitary-adrenal axis, Fos-like immunoreactivity, restraint stress, hemorrhage, cold exposure, pain, hypoglycemia
MeSH terms: Adrenocorticotropic Hormone, Animals, Brain, Humans, Hypothalamo-Hypophyseal System, Neurosecretory Systems, Paraventricular Hypothalamic Nucleus, Stress, Physiological

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Stressor specificity of central neuroendocrine responses: implications for stress-related disorders

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