Structural and functional evolution of vertebrate neuroendocrine stress systems
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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Fear, anxiety, and aggression are stress responses, mediated across vertebrates by the hypothalamic-pituitary-adrenal (HPA) axis.
“Fear, anxiety, and aggression are stress responses, mediated across vertebrates by the hypothalamic-pituitary-adrenal (HPA) axis (Denver, 2009;Haller, 2014), the hypofunction of which has been proposed as a key mechanism in the development of tame behaviors in domesticates (Trut et al., 2009;Wilkins et al., 2014).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Denver, 2009
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Endocrinology of Complex Life Cycles: Amphibians
Denver, R. J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803592-4.00024-9 · Cited by 34 · see citing works
Interaction mechanisms between major depressive disorder and non-alcoholic fatty liver disease
Shao, Q., Wu, Y., Ji, J., Xu, T., Yu, Q., Ma, C., Liao, X., Cheng, F., & Wang, X. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.711835 · Cited by 32 · see citing works
Cortisol, Stress, and Disease—Bidirectional Associations; Role for Corticosteroid-Binding Globulin?
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Conservation aquaculture—A sturgeon story
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Environmental Sex Determination and Sex Differentiation in Teleosts – How Sex Is Established
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Validation of hippocampal biomarkers of cumulative affective experience
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The evolution of a series of behavioral traits is associated with autism-risk genes in cavefish
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Hypothalamic CRF neurons facilitate brain reward function
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Neuroendocrine changes upon exposure to predator odors
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The biological significance of acoustic stimuli determines ear preference in the music frog
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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
- 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
- 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
- Social Sciences › Psychology › Social Psychology › 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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