Glucocorticoid receptor function correlates with behavioral outcomes
Extensive preclinical and clinical evidence demonstrates that glucocorticoid receptor function and sensitivity are directly correlated with behavioral outcomes, particularly regarding stress adaptation, anxiety, and depression-like phenotypes.
The retrieved literature consistently links glucocorticoid receptor (GR) signaling, expression, phosphorylation, and negative feedback sensitivity to behavioral outcomes such as anxiety, depression-like behaviors, and stress resilience. Multiple papers report that alterations in GR function across different brain regions correspond to varying behavioral phenotypes and stress-related disorders, thus supporting the claim.
Michael Murack, Rajini Chandrasegaram, Kevin Smith, Emily G. Ah-Yen, Étienne Rhéaume, Étienne Malette-Guyon, Zahra Nanji, Seana N. Semchishen, Olivia Latus, C. Messier, N. Ismail. Chronic Sleep Disruption induces depression-like behavior in adolescent male and female mice and sensitization of the hypothalamic-pituitary-adrenal axis in adolescent female mice.. 2020. https://doi.org/10.1016/j.bbr.2020.113001
Study links glucocorticoid receptor expression and cellular activation in brain regions to depression-like behaviors following sleep disruption.
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T. Göver, M. Slezak. Targeting glucocorticoid receptor signaling pathway for treatment of stress-related brain disorders. 2024. https://doi.org/10.1007/s43440-024-00654-w
Review highlights how aberrant glucocorticoid receptor signaling translates to altered behavior in stress-related disorders.
Da-Neng Wei, Yafei Zhao, Mengmeng Zhang, Lei Zhu, Li Wang, Xing Yuan, Chunjie Wu. The Volatile Oil of Zanthoxylum bungeanum Pericarp Improved the Hypothalamic-Pituitary-Adrenal Axis and Gut Microbiota to Attenuate Chronic Unpredictable Stress-Induced Anxiety Behavior in Rats. 2021. https://doi.org/10.2147/DDDT.S281575
Shows that treatments improving anxiety behavior concomitantly elevate glucocorticoid receptor expression in the hypothalamus.
N. Goncharova, O. Chigarova, N. Rudenko, T. Oganyan. Glucocorticoid Negative Feedback in Regulation of the Hypothalamic-Pituitary-Adrenal Axis in Rhesus Monkeys With Various Types of Adaptive Behavior: Individual and Age-Related Differences. 2019. https://doi.org/10.3389/fendo.2019.00024
Demonstrates that individual differences in glucocorticoid receptor feedback regulation correlate with trait anxiety and depression-like behavior.
Bao-Lun Zhu, Jin Tang, W. Chen, Jun-Jie Qian, Feng Zhang, Xiao-Ling Zhang, Tingting Chen, Bo Jiang, He-Yan Zhao. Fluoxetine treatment reverses chronic stress-induced promotion on Fk506-binding protein 5 expression and multiple effects on glucocorticoid receptor phosphorylation in the paraventricular nucleus of mice.. 2024. https://doi.org/10.1016/j.pbb.2024.173916
Connects changes in glucocorticoid receptor phosphorylation and coregulators in the paraventricular nucleus to depression-like behaviors and antidepressant responses.
Ritter P, Shuliupova A, Reshetnikov V, Bondar N. Phenotype-Specific Transcriptomic Responses to Glucocorticoid Signaling in the Prefrontal Cortex and Dorsal Raphe Nucleus Following Chronic Social Stress.. 2026. https://doi.org/10.3390/ijms27146442
Finds that chronic stress establishes distinct behavioral phenotypes that shape glucocorticoid-responsive transcriptional programs.
Potapova S, Isakov Y, Tyulkova E, Vetrovoy O. Glucocorticoid Receptor Signaling: Multilevel Organization, Roles in Fetal Development, and Postnatal Outcomes.. 2026. https://doi.org/10.3390/ijms27062873
Explains how long-term variation in glucocorticoid receptor sensitivity and axis regulation manifests as differences in stress reactivity and affective trajectories.
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