Chronic stress alters adrenal clock function in a sexually dimorphic manner

Stagl, Matthew; Bozsik, Mary; Karow, Christopher; Wertz, David; Kloehn, Ian; Gasser, P.; Gilmartin, Marieke R.; Evans, Jennifer

doi:10.1530/jme-17-0146

Cited by 11 publications

(5 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sex differences have been described at many levels of the circadian system, including in relation to SCN size and HPA axis vulnerability (Bailey & Silver 2014). This leads to a different response and resilience to circadian 'challenges' such as stress: in fact, the adrenal clock seems to have a gating effect on stress response in a sexually dimorphic manner, with ACTH exerting a larger response from female adrenal glands, possibly due to the lower amplitude of the adrenal clock oscillation (Stagl et al 2018). In summary, glucocorticoids and glucocorticoid receptor (GR) are important in re-shaping the cosinor-based rhytmometry, but they are not the only agents involved (Fig.…”

Section: The Vertical Paradigm: Hierarchical Control Of the Hpa Circamentioning

confidence: 99%

Fixing the broken clock in adrenal disorders: focus on glucocorticoids and chronotherapy

Minnetti

Hasenmajer

Pofi

et al. 2020

Journal of Endocrinology

View full text Add to dashboard Cite

The circadian rhythm derives from the integration of many signals that shape the expression of clock-related genes in a 24-h cycle. Biological tasks, including cell proliferation, differentiation, energy storage, and immune regulation, are preferentially confined to specific periods. A gating system, supervised by the central and peripheral clocks, coordinates the endogenous and exogenous signals and prepares for transition to activities confined to periods of light or darkness. The fluctuations of cortisol and its receptor are crucial in modulating these signals. Glucocorticoids and the autonomous nervous system act as a bridge between the suprachiasmatic master clock and almost all peripheral clocks. Additional peripheral synchronizing mechanisms including metabolic fluxes and cytokines stabilize the network. The pacemaker is amplified by peaks and troughs in cortisol and their response to food, activity, and inflammation. However, when the glucocorticoid exposure pattern becomes chronically flattened at high- (as in Cushing’s syndrome) or low (as in adrenal insufficiency) levels, the system fails. While endocrinologists are well aware of cortisol rhythm, too little attention has been given to interventions aimed at restoring physiological cortisol fluctuations in adrenal disorders. However, acting on glucocorticoid levels may not be the only way to restore clock-related activities. First, a counterregulatory mechanism on the glucocorticoid receptor itself controls signal transduction, and second, melatonin and/or metabolically active drugs and nutrients could also be used to modulate the clock. All these aspects are described herein, providing some insights into the emerging role of chronopharmacology, focusing on glucocorticoid excess and deficiency disorders.

show abstract

Section: The Vertical Paradigm: Hierarchical Control Of the Hpa Circamentioning

confidence: 99%

Fixing the broken clock in adrenal disorders: focus on glucocorticoids and chronotherapy

Minnetti

Hasenmajer

Pofi

et al. 2020

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Cortisol downregulates the blood concentration of CRH and ACTH via different negative feedback mechanisms [44]. The secretion of cortisol and other glucocorticoids from the adrenal gland is dynamically regulated throughout the day [45]. These hormones are released in higher amounts at the beginning of the active phase of the circadian cycle.…”

Section: Discussionmentioning

confidence: 99%

Effects of Withania somnifera on Cortisol Levels in Stressed Human Subjects: A Systematic Review

Della Porta,

Maier,

Cazzola

2023

Nutrients

View full text Add to dashboard Cite

Background: Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and anti-stress activities. However, its precise mechanisms of action and optimal use as a supplement are not yet fully understood. The objective of this systematic review is to assess the impact of WS supplementation on cortisol levels in stressed humans by analyzing clinical trials conducted prior to May 2023. Methods: The assessment was carried out following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) by exploring the databases of EMBASE, PubMed, Google Scholar, CENTRAL, and Scopus. Results: Of the 4788 articles identified, only 9 studies met the selection criteria. The selected studies varied in terms of design, results, formulations, dosages, and treatment duration (30–112 days), and involved subjects with varying degrees of stress. WS supplementation decreases cortisol secretion with no significant adverse effects. Nonetheless, none of the studies evaluated the potential impact of cortisol reduction on adrenal function and long-term effects. Conclusions: Brief-term supplementation with WS appears to have a stress-reducing effect in stressed individuals. However, since the long-term effects of WS supplementation are not yet fully understood, WS supplements should be used under medical supervision.

show abstract

“…Restraint stress applied for 15 min advanced adrenal PER2::LUC oscillation by 2 h ( Engeland et al, 2016 ). In another study, 2 h restraint starting during the mid-day didn’t shift adrenal PER2::LUC expression, but repeating the regimen for 7 days did do so ( Stagl et al, 2018 ). Finally, 14 days of subordination stress also led to advanced PER2::LUC in the adrenal glands ( Razzoli et al, 2014 ).…”

Section: Differential Afferent Inputs To Peripheral and Scn Clocksmentioning

confidence: 99%

Mutual Shaping of Circadian Body-Wide Synchronization by the Suprachiasmatic Nucleus and Circulating Steroids

Yao

Silver

2022

Front. Behav. Neurosci.

View full text Add to dashboard Cite

BackgroundSteroids are lipid hormones that reach bodily tissues through the systemic circulation, and play a major role in reproduction, metabolism, and homeostasis. All of these functions and steroids themselves are under the regulation of the circadian timing system (CTS) and its cellular/molecular underpinnings. In health, cells throughout the body coordinate their daily activities to optimize responses to signals from the CTS and steroids. Misalignment of responses to these signals produces dysfunction and underlies many pathologies.Questions AddressedTo explore relationships between the CTS and circulating steroids, we examine the brain clock located in the suprachiasmatic nucleus (SCN), the daily fluctuations in plasma steroids, the mechanisms producing regularly recurring fluctuations, and the actions of steroids on their receptors within the SCN. The goal is to understand the relationship between temporal control of steroid secretion and how rhythmic changes in steroids impact the SCN, which in turn modulate behavior and physiology.Evidence SurveyedThe CTS is a multi-level organization producing recurrent feedback loops that operate on several time scales. We review the evidence showing that the CTS modulates the timing of secretions from the level of the hypothalamus to the steroidogenic gonadal and adrenal glands, and at specific sites within steroidogenic pathways. The SCN determines the timing of steroid hormones that then act on their cognate receptors within the brain clock. In addition, some compartments of the body-wide CTS are impacted by signals derived from food, stress, exercise etc. These in turn act on steroidogenesis to either align or misalign CTS oscillators. Finally this review provides a comprehensive exploration of the broad contribution of steroid receptors in the SCN and how these receptors in turn impact peripheral responses.ConclusionThe hypothesis emerging from the recognition of steroid receptors in the SCN is that mutual shaping of responses occurs between the brain clock and fluctuating plasma steroid levels.

show abstract

Chronic stress alters adrenal clock function in a sexually dimorphic manner

Cited by 11 publications

References 64 publications

Fixing the broken clock in adrenal disorders: focus on glucocorticoids and chronotherapy

Fixing the broken clock in adrenal disorders: focus on glucocorticoids and chronotherapy

Effects of Withania somnifera on Cortisol Levels in Stressed Human Subjects: A Systematic Review

Mutual Shaping of Circadian Body-Wide Synchronization by the Suprachiasmatic Nucleus and Circulating Steroids

Contact Info

Product

Resources

About