Hypothalamic-pituitary – adrenal axis-feedback control

Keller‐Wood, Maureen

doi:10.1002/cphy.c140065

Cited by 131Stress Responses and CortisolAdrenal Hormones and DisordersNeuropeptides and Animal Physiology

Hypothalamic-pituitary – adrenal axis-feedback control

Keller‐Wood, Maureen·2015·Comprehensive Physiology

DOI 10.1002/cphy.c140065

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Abstract

The hypothalamo-pituitary-adrenal axis (HPA) is responsible for stimulation of adrenal corticosteroids in response to stress. Negative feedback control by corticosteroids limits pituitary secretion of corticotropin, ACTH, and hypothalamic secretion of corticotropin-releasing hormone, CRH, and vasopressin, AVP, resulting in regulation of both basal and stress-induced ACTH secretion. The negative feedback effect of corticosteroids occurs by action of corticosteroids at mineralocorticoid receptors (MR) and/or glucocorticoid receptors (GRs) located in multiple sites in the brain and in the pituitary. The mechanisms of negative feedback vary according to the receptor type and location within the brain-hypothalmo-pituitary axis. A very rapid nongenomic action has been demonstrated for GR action on CRH neurons in the hypothalamus, and somewhat slower nongenomic effects are observed in the pituitary or other brain sites mediated by GR and/or MR. Corticosteroids also have genomic actions, including repression of the pro-opiomelanocortin (POMC) gene in the pituitary and CRH and AVP genes in the hypothalamus. The rapid effect inhibits stimulated secretion, but requires a rapidly rising corticosteroid concentration. The more delayed inhibitory effect on stimulated secretion is dependent on the intensity of the stimulus and the magnitude of the corticosteroid feedback signal, but also the neuroanatomical pathways responsible for activating the HPA. The pathways for activation of some stressors may partially bypass hypothalamic feedback sites at the CRH neuron, whereas others may not involve forebrain sites; therefore, some physiological stressors may override or bypass negative feedback, and other psychological stressors may facilitate responses to subsequent stress.

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Glucocorticoid feedback negatively on the pituitary and hypothalamus to inhibit ACTH secretion.
“From an endocrine perspective, a key role of glucocorticoid is to feedback negatively on the pituitary and hypothalamus to inhibit ACTH secretion (17).”
From ACTH Antagonists (2016) · cites this paper as [17]

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Authors: Keller‐Wood, M.
Venue: Comprehensive Physiology
Publisher: Wiley
Published: 2015-06-24
Volume: 5
Issue: 3
Pages: 1161-1182
ISSN: 2040-4603 (ISSN-L)
DOI: 10.1002/cphy.c140065
OpenAlex: W1515955887
Cited by: 131
References: 324
Citations by year: 2026: 7 · 2025: 7 · 2024: 15 · 2023: 15 · 2022: 15 · 2021: 13 · 2020: 11 · 2019: 13 · 2018: 15 · 2017: 9 · 2016: 11
Type: other
Language: en
Open access: closed
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm)
Locations: Comprehensive physiology (publishedVersion)
PubMed (publishedVersion)
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 › Neuropeptides and Animal Physiology
Keywords: hypothalamic-pituitary-adrenal axis, negative feedback, corticosteroids, ACTH secretion, corticotropin-releasing factor, vasopressin, mineralocorticoid receptor, glucocorticoid receptor, non-genomic steroid action, proopiomelanocortin, stress response, psychological stress
MeSH terms: Animals, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Feedback, Physiological

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Hypothalamic-pituitary – adrenal axis-feedback control

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