ArticleEndocrinology2017
Modeling the Sex Differences and Interindividual Variability in the Activity of the Hypothalamic-Pituitary-Adrenal Axis.
Article in Endocrinology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed.
- Infant cortisol stress-response is associated with thymic function and vaccine response.Stress (Amsterdam, Netherlands) · 2019Trial
- From Infection to Anxiety: A Sequential Model Linking Latent Toxoplasmosis to Psychological Distress via Health and Stress.Scandinavian journal of psychology · 2026Article
- Prenatal stress alters offspring neurovascular, autonomic, and immune development in animal models of neuropsychiatric and cardiometabolic disorders.Journal of neuroendocrinology · 2026Review
- Sex-Specific Responses to Intermittent Fasting: A Narrative Review Across Physiological, Clinical, and Psychosocial Contexts.Nutrients · 2026Review
- Elevated serum cortisol associated with early-detected increase of brain amyloid deposition in Alzheimer's disease imaging biomarkers among menopausal women: The Framingham Heart Study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Quantitative Assessment of Psychological Stress Changes Before and After Ureteral Stent Placement: A Prospective Observational Study.Patient preference and adherence · 2025Article
- The Physiological and Pharmacological Significance of the Circadian Timing of the HPA Axis: A Mathematical Modeling Approach.Journal of pharmaceutical sciences · 2024Review
- Mathematical modeling of temperature-induced circadian rhythms.Frontiers in systems biology · 2024Article
- The SCN-HPA-Periphery Circadian Timing System: Mathematical Modeling of Clock Synchronization and the Effects of Photoperiod on Jetlag Adaptation.Journal of biological rhythms · 2023Article
- The stress of losing sleep: Sex-specific neurobiological outcomes.Neurobiology of stress · 2023Article
- The rearing environment persistently modulates mouse phenotypes from the molecular to the behavioural level.PLoS biology · 2022Article
- Modelling the dynamic interaction of systemic inflammation and the hypothalamic-pituitary-adrenal (HPA) axis during and after cardiac surgery.Journal of the Royal Society, Interface · 2022Article
- Neurobehavioral abnormalities following prenatal psychosocial stress are differentially modulated by maternal environment.Translational psychiatry · 2022Article
- The role of the type 7 adenylyl cyclase isoform in alcohol use disorder and depression.Frontiers in pharmacology · 2022Review
- Impact of stress resilience and susceptibility on fear learning, anxiety, and alcohol intake.Neurobiology of stress · 2021Article
- Serum-Derived Neuronal Exosomal miRNAs as Biomarkers of Acute Severe Stress.International journal of molecular sciences · 2021Article
- Light entrainment of the SCN circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag.Scientific reports · 2021Article
- Modeling the Influence of Chronic Sleep Restriction on Cortisol Circadian Rhythms, with Implications for Metabolic Disorders.Metabolites · 2021Article
- Circadian rhythms and the HPA axis: A systems view.WIREs mechanisms of disease · 2021Review
- Sex differences in the association between childhood maltreatment and cardiovascular disease in the UK Biobank.Heart (British Cardiac Society) · 2020Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Significant sex differences exist in the activity of the hypothalamic-pituitary-adrenal (HPA) axis. These differences are thought to contribute to the disparity in the prevalence of various autoimmune and infectious diseases between males and females. We used a mathematical model of the HPA axis to evaluate the hypothesis that differential sensitivity and negative feedback of the HPA axis network are causal factors for the observed sex differences in its activity. In doing so, we implicitly accounted for the differential influence of gonadal hormones on the HPA axis. Furthermore, we determined whether the putative mechanisms responsible for differences in basal HPA axis activity might also contribute to the observed differences in its stimulus-driven response. Model simulations predicted that the female HPA axis has greater adrenal sensitivity and weaker negative feedback. We identified two distinct sex-specific parameter spaces that generate corticosterone profiles in qualitative agreement with experimental results. We propose that these parameter subspaces indicate the interindividual variability in the regulatory mechanisms of the HPA axis. Furthermore, the model predicts that the maintenance of homeostatic rhythms in response to chronic stress requires specific regulatory adaptations resulting in a phenotype of allostatically driven chronic stress-sensitization. We propose that these adaptations indicate a physiological cost of adaptation to chronic stress. Model simulations suggest that individuals with high adrenal sensitivity are more vulnerable to chronic stress sensitization and might be more susceptible to the development of neuropsychiatric disorders. These results contribute to the study of sex differences in physiological feedback systems within a quantitative framework.
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