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Cited by 1,586Stress Responses and CortisolRegulation of Appetite and ObesityAdrenal Hormones and Disorders

Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo–pituitary–adrenocortical responsiveness

Herman, James P., Figueiredo, Helmer, Mueller, Nancy K., Ulrich-Lai, Yvonne, Ostrander, Michelle M., Choi, Dennis C., Cullinan, William E.·2003·Frontiers in Neuroendocrinology
DOI 10.1016/j.yfrne.2003.07.001
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Abstract

Appropriate regulatory control of the hypothalamo-pituitary-adrenocortical stress axis is essential to health and survival. The following review documents the principle extrinsic and intrinsic mechanisms responsible for regulating stress-responsive CRH neurons of the hypothalamic paraventricular nucleus, which summate excitatory and inhibitory inputs into a net secretory signal at the pituitary gland. Regions that directly innervate these neurons are primed to relay sensory information, including visceral afferents, nociceptors and circumventricular organs, thereby promoting 'reactive' corticosteroid responses to emergent homeostatic challenges. Indirect inputs from the limbic-associated structures are capable of activating these same cells in the absence of frank physiological challenges; such 'anticipatory' signals regulate glucocorticoid release under conditions in which physical challenges may be predicted, either by innate programs or conditioned stimuli. Importantly, 'anticipatory' circuits are integrated with neural pathways subserving 'reactive' responses at multiple levels. The resultant hierarchical organization of stress-responsive neurocircuitries is capable of comparing information from multiple limbic sources with internally generated and peripherally sensed information, thereby tuning the relative activity of the adrenal cortex. Imbalances among these limbic pathways and homeostatic sensors are likely to underlie hypothalamo-pituitary-adrenocortical dysfunction associated with numerous disease processes.

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Crossref · 10.1016/j.yfrne.2003.07.001

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  • The stress response system receives complex information about the external environment through limbic structures and about the organism from other neuroendocrine systems.

    “The SRS receives complex information about the external environment through limbic structures, and complex information about the organism from interaction with other neuroendocrine systems (e.g., the HPG axis6 and the immune system; see Herman et al., 2003)”

    From The Adaptive Calibration Model of stress responsivity (2011) · cites this paper as Herman et al., 2003

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Authors
Herman, J. P., Figueiredo, H., Mueller, N. K., Ulrich-Lai, Y., Ostrander, M. M., Choi, D. C., & Cullinan, W. E.
Affiliations
  • University of Cincinnati (US)
  • Marquette University (US)
Corresponding author
Herman, James P.
ORCID
Herman, James P.
Venue
Frontiers in Neuroendocrinology
Publisher
Elsevier BV
Published
2003-07
Volume
24
Issue
3
Pages
151-180
ISSN
0091-3022 (ISSN-L)
DOI
10.1016/j.yfrne.2003.07.001
OpenAlex
W1979295154
Cited by
1,586
References
335
Citations by year
2026: 23 · 2025: 31 · 2024: 38 · 2023: 47 · 2022: 67 · 2021: 68 · 2020: 66 · 2019: 68 · 2018: 73 · 2017: 89 · 2016: 96 · 2015: 72 · 2014: 86 · 2013: 100 · 2012: 89
FWCI
19.58
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Frontiers in Neuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5f32mh065770-02, 5r29mh056577-05, 5r03mh060819-03)
  • National Institute of Mental Health (MH 60819, MH49698, MH56577, MH65770)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
hypothalamic-pituitary-adrenal axis, stress response, corticotropin-releasing hormone neurons, paraventricular nucleus, stress integration, anticipatory stress, limbic system, visceral afferents, nociceptors, circumventricular organs, adrenal cortex, neurocircuitry, homeostatic regulation
MeSH terms
Adrenocorticotropic Hormone, Amygdala, Animals, Corticotropin-Releasing Hormone, Glucocorticoids, Hippocampus, Humans, Hypothalamo-Hypophyseal System, Hypothalamus, Limbic System, Paraventricular Hypothalamic Nucleus, Pituitary-Adrenal System, Raphe Nuclei, Septal Nuclei, Stress, Physiological, Thalamus, Prefrontal Cortex, Solitary Nucleus

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