Glucocorticoid receptor signaling in health and disease

Kadmiel, Mahita; Cidlowski, John A.

doi:10.1016/j.tips.2013.07.003

Cited by 849Estrogen and related hormone effectsAdrenal Hormones and DisordersStress Responses and Cortisol

Glucocorticoid receptor signaling in health and disease

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Kadmiel, Mahita, Cidlowski, John A.·2013·Trends in Pharmacological Sciences

DOI 10.1016/j.tips.2013.07.003PMC PMC3951203

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Abstract

Glucocorticoids are steroid hormones regulated in a circadian and stress-associated manner to maintain various metabolic and homeostatic functions that are necessary for life. Synthetic glucocorticoids are widely prescribed drugs for many conditions including asthma, chronic obstructive pulmonary disease (COPD), and inflammatory disorders of the eye. Research in the past few years has begun to unravel the profound complexity of glucocorticoid signaling and has contributed remarkably to improved therapeutic strategies. Glucocorticoids signal through the glucocorticoid receptor (GR), a member of the superfamily of nuclear receptors, in both genomic and non-genomic ways in almost every tissue in the human body. In this review, we provide an update on glucocorticoid receptor signaling and highlight the role of GR signaling in physiological and pathophysiological conditions in the major organ systems in the human body.

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The HPA axis is regulated by a negative feedback mechanism in which ACTH and cortisol inhibit CRH and ACTH secretion, maintaining homeostasis.
“This system is regulated by a negative feedback mechanism, in which both ACTH and cortisol act as inhibitors of CRH and ACTH secretion, thereby maintaining homeostasis [16,17].”
From Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation (2025) · cites this paper as [17]
The Glucocorticoids section (page unavailable) says the HPA axis regulates cortisol release, and the Nervous system section (page unavailable) says forebrain glucocorticoid receptors regulate the HPA axis. Neither passage describes negative feedback or says that ACTH and cortisol inhibit CRH and ACTH secretion. (LLM, conf=0.78)
Experimental — accuracy not yet measured
Pro-inflammatory cytokines participate in a positive feedback loop that increases stimulation of CRH and ACTH release.
“Moreover, these pro-inflammatory cytokines participate in a positive feedback loop that increases the stimulation of CRH and ACTH release [17].”
From Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation (2025) · cites this paper as [17]
The Glucocorticoids section (page unavailable) says the HPA axis regulates glucocorticoid release, and the Immune System section (page unavailable) discusses pro-inflammatory cytokine release. Neither connects cytokines to increased CRH or ACTH release or describes the claimed positive feedback loop. Searches for CRH, ACTH, and cytokine–HPA feedback found no passage establishing that link. (LLM, conf=0.73)
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Authors: Kadmiel, M., & Cidlowski, J. A.
Affiliations: National Institutes of Health (US)
Corresponding author: Cidlowski, John A.
ORCID: Cidlowski, John A.
Venue: Trends in Pharmacological Sciences
Publisher: Elsevier BV
Published: 2013-09
Volume: 34
Issue: 9
Pages: 518-530
ISSN: 0165-6147 (ISSN-L)
DOI: 10.1016/j.tips.2013.07.003
PMC: PMC3951203
OpenAlex: W2034836489
Cited by: 849
References: 112
Citations by year: 2026: 45 · 2025: 66 · 2024: 69 · 2023: 77 · 2022: 73 · 2021: 90 · 2020: 77 · 2019: 76 · 2018: 56 · 2017: 80 · 2016: 57 · 2015: 47 · 2014: 33 · 2013: 1 · 2012: 1
FWCI: 5.66
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Pharmacological Sciences (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (Z99-ES999999)
National Institute of Environmental Health Sciences (Z01ES090057, Z01ES090079)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: glucocorticoid receptor, glucocorticoid signaling, nuclear receptors, genomic signaling, non-genomic signaling, steroid hormones, circadian regulation, stress response, asthma, chronic obstructive pulmonary disease, glucocorticoid therapy
MeSH terms: Animals, Humans, Receptors, Glucocorticoid, Signal Transduction

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Glucocorticoid receptor signaling in health and disease

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