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

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

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