Cited by 273Stress Responses and CortisolNeuropeptides and Animal PhysiologyNeuroendocrine regulation and behavior

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Structural and Functional Evolution of Vertebrate Neuroendocrine Stress Systems

Denver, Robert John·2009·Annals of the New York Academy of Sciences

DOI 10.1111/j.1749-6632.2009.04433.x

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Abstract

The vertebrate hypothalamus-pituitary-adrenal (HPA; or interrenal) axis plays pivotal roles in animal development and in physiological and behavioral adaptation to environmental change. The HPA, or stress axis, is organized in a hierarchical manner, with feedback operating at several points along the axis. Recent findings suggest that the proteins, gene structures, and signaling pathways of the HPA axis were present in the earliest vertebrates and have been maintained by natural selection owing to their critical adaptive roles. In all vertebrates studied, the HPA axis is activated in response to stressors and is controlled centrally by peptides of the corticotropin-releasing factor (CRF) family of which four paralogous members have been identified. Signaling by CRF-like peptides is mediated by at least two distinct G protein-coupled receptors and modulated by a secreted binding protein. These neuropeptides function as hypophysiotropins and as neurotransmitters/neuromodulators, influencing stress-related behaviors, such as anxiety and fear. In addition to modulating HPA activity and behavioral stress responses, CRF-like peptides are implicated in timing key life history transitions, such as metamorphosis in amphibians and birth in mammals. CRF-like peptides and signaling components are also expressed outside of the central nervous system where they have diverse physiological functions. Glucocorticoids are the downstream effectors of the HPA axis, playing essential roles in development, energy balance and behavior, and feedback actions on the activity of the HPA axis.

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Authors: Denver, R. J.
Affiliations: University of Michigan (US)
Corresponding author: Denver, Robert John
ORCID: Denver, Robert John
Venue: Annals of the New York Academy of Sciences
Publisher: Wiley
Published: 2009-04
Volume: 1163
Issue: 1
Pages: 1-16
ISSN: 0077-8923 (ISSN-L)
1749-6632
DOI: 10.1111/j.1749-6632.2009.04433.x
OpenAlex: W2115078524
Cited by: 273
References: 141
Citations by year: 2026: 10 · 2025: 18 · 2024: 19 · 2023: 23 · 2022: 19 · 2021: 18 · 2020: 17 · 2019: 13 · 2018: 14 · 2017: 11 · 2016: 19 · 2015: 13 · 2014: 8 · 2013: 16 · 2012: 10
FWCI: 0.96
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 26 d)
Locations: Annals of the New York Academy of Sciences (publishedVersion)
PubMed (publishedVersion)
Deep Blue (University of Michigan) (submittedVersion)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
Keywords: hypothalamic-pituitary-adrenal axis, corticotropin-releasing factor, G protein-coupled receptors, glucocorticoids, evolutionary conservation, vertebrate development, life-history transitions, metamorphosis, fear and anxiety, glucocorticoid feedback, neuropeptides
MeSH terms: Animals, Biological Evolution, Humans, Hypothalamus, Neurosecretory Systems, Pituitary-Adrenal System, Stress, Physiological, Vertebrates

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Structural and Functional Evolution of Vertebrate Neuroendocrine Stress Systems

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