Cited by 277Stress Responses and CortisolAdrenal Hormones and DisordersNeuroscience and Neuropharmacology Research

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Mechanisms of rapid glucocorticoid feedback inhibition of the hypothalamic–pituitary–adrenal axis

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Tasker, Jeffrey G., Herman, James P.·2011·Stress

DOI 10.3109/10253890.2011.586446PMC PMC4675656

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Abstract

Stress activation of the hypothalamic-pituitary-adrenal (HPA) axis culminates in increased circulating corticosteroid concentrations. Stress-induced corticosteroids exert diverse actions in multiple target tissues over a broad range of timescales, ranging from rapid actions, which are induced within seconds to minutes and gene transcription independent, to slow actions, which are delayed, long lasting, and transcription dependent. Rapid corticosteroid actions in the brain include, among others, a fast negative feedback mechanism responsible for shutting down the activated HPA axis centrally. We provide a brief review of the cellular mechanisms responsible for rapid corticosteroid actions in different brain structures of the rat, including the hypothalamus, hippocampus, amygdala, and in the anterior pituitary. We propose a model for the direct feedback inhibition of the HPA axis by glucocorticoids in the hypothalamus. According to this model, glucocorticoids activate membrane glucocorticoid receptors to induce endocannabinoid synthesis in the hypothalamic paraventricular nucleus (PVN) and retrograde cannabinoid type I receptor-mediated suppression of the excitatory synaptic drive to PVN neuroendocrine cells. Rapid corticosteroid actions in the hippocampus, amygdala, and pituitary are mediated by diverse cellular mechanisms and may also contribute to the rapid negative feedback regulation of the HPA neuroendocrine axis as well as to the stress regulation of emotional and spatial memory formation.

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Authors: Tasker, J. G., & Herman, J. P.
Affiliations: Tulane University (US)
University of Cincinnati (US)
Corresponding author: Tasker, Jeffrey G.
ORCID: Tasker, Jeffrey G.
Herman, James P.
Venue: Stress
Publisher: Informa UK Limited
Published: 2011-06-11
Volume: 14
Issue: 4
Pages: 398-406
ISSN: 1025-3890 (ISSN-L)
1607-8888
DOI: 10.3109/10253890.2011.586446
PMC: PMC4675656
OpenAlex: W1754265819
Cited by: 277
References: 70
Citations by year: 2026: 8 · 2025: 8 · 2024: 18 · 2023: 7 · 2022: 18 · 2021: 19 · 2020: 21 · 2019: 27 · 2018: 16 · 2017: 19 · 2016: 21 · 2015: 25 · 2014: 22 · 2013: 21 · 2012: 21
FWCI: 8.79
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Stress (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (MH049698)
National Institute of Mental Health (MH066958, MH069879, R01MH066958, R01MH069879, R01MH049698, MH 069725, MH049698, R01MH069725)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: glucocorticoid negative feedback, hypothalamic-pituitary-adrenal axis, endocannabinoids, paraventricular nucleus, hippocampus, amygdala, anterior pituitary, neuroendocrine regulation, emotional memory, spatial memory
MeSH terms: Amygdala, Animals, Glucocorticoids, Hippocampus, Hypothalamo-Hypophyseal System, Neurons, Paraventricular Hypothalamic Nucleus, Pituitary-Adrenal System, Receptors, Glucocorticoid, Feedback, Physiological, Receptor, Cannabinoid, CB1, Rats, Cannabinoid Receptor Modulators

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Mechanisms of rapid glucocorticoid feedback inhibition of the hypothalamic–pituitary–adrenal axis

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