ArticleJournal of the Royal Society, Interface2015
Rapid intra-adrenal feedback regulation of glucocorticoid synthesis.
Article in Journal of the Royal Society, Interface, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 69 citations in OpenAlex.
- Use of corticosteroids in sepsis and infectious diseases: a narrative review.The Korean journal of internal medicine · 2026Review
- The Glucocorticoid Receptor Co-Chaperone FKBP51 in the Adrenal Cortex Is Not Involved in Regulating Hypothalamic-Pituitary-Adrenal Activity in the Mouse.The European journal of neuroscience · 2025Article
- Modulation of glucocorticoid receptor function under iron overload.Frontiers in immunology · 2025Article
- Biological Basis for the Formation of Suicidal Behavior: A Review.Medical journal of the Islamic Republic of Iran · 2025Review
- Modelling the role of glucocorticoid receptor as mediator of endocrine responses to environmental challenge.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Article
- Peripheral glucocorticoid receptor antagonism by relacorilant with modest HPA axis disinhibition.The Journal of endocrinology · 2023Article
- The Role of Glucocorticoids in Breast Cancer Therapy.Current oncology (Toronto, Ont.) · 2022Review
- Integrating orientation mechanisms, adrenocortical activity, and endurance flight in vagrancy behaviour.Scientific reports · 2022Article
- ARMC5 is part of an RPB1-specific ubiquitin ligase implicated in adrenal hyperplasia.Nucleic acids research · 2022Article
- Septic Shock: A Disruptor of the Hypothalamic-Adrenal Axis as We Know It.Endocrinology · 2022Article
- Is PTSD-Phenotype Associated with HPA-Axis Sensitivity?: The Endocannabinoid System in Modulating Stress Response in Rats.International journal of molecular sciences · 2021Article
- Is PTSD-Phenotype Associated with HPA-Axis Sensitivity? Feedback Inhibition and Other Modulating Factors of Glucocorticoid Signaling Dynamics.International journal of molecular sciences · 2021Article
- Distinctive gene expression patterns and imprinting signatures revealed in reciprocal crosses between cattle sub-species.BMC genomics · 2021Article
- Article
- Mathematical modeling of depressive disorders: Circadian driving, bistability and dynamical transitions.Computational and structural biotechnology journal · 2021Article
- Bidirectional Crosstalk Between Hypoxia Inducible Factors and Glucocorticoid Signalling in Health and Disease.Frontiers in immunology · 2021Review
- Dynamics of ACTH and Cortisol Secretion and Implications for Disease.Endocrine reviews · 2020Review
- Glucocorticoids in Sepsis: To Be or Not to Be.Frontiers in immunology · 2020Review
- Short treatment with antalarmin alters adrenal gland receptors in the rat model of endometriosis.PloS one · 2020Article
- Mathematical Modelling of Endocrine Systems.Trends in endocrinology and metabolism: TEM · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The hypothalamic-pituitary-adrenal axis is a vital neuroendocrine system that regulates the secretion of glucocorticoid hormones from the adrenal glands. This system is characterized by a dynamic ultradian hormonal oscillation, and in addition is highly responsive to stressful stimuli. We have recently shown that a primary mechanism generating this ultradian rhythm is a systems-level interaction where adrenocorticotrophin hormone (ACTH) released from the pituitary stimulates the secretion of adrenal glucocorticoids, which in turn feedback at the level of the pituitary to rapidly inhibit ACTH secretion. In this study, we combine experimental physiology and mathematical modelling to investigate intra-adrenal mechanisms regulating glucocorticoid synthesis. Our modelling results suggest that glucocorticoids can inhibit their own synthesis through a very rapid (within minutes), presumably non-genomic, intra-adrenal pathway. We present further evidence for the existence of a short time delay in this intra-adrenal inhibition, and also that at the initiation of each ACTH stimulus, this local feedback mechanism is rapidly antagonized, presumably via activation of the specific ACTH receptor (MC2R) signalling pathway. This mechanism of intra-adrenal inhibition enables the gland to rapidly release glucocorticoids while at the same time preventing uncontrolled release of glucocorticoids in response to large surges in ACTH associated with stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.