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Published on: March 5, 2022
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Polycystic Ovary Syndrome Pathophysiology: Integrating Systemic, CNS and Circadian Processes
1CRC Scotland & London, SW1V 1PG London, UK.
Frontiers in Bioscience (Landmark Edition)
|January 30, 2024
Summary
Polycystic ovary syndrome (PCOS) involves more than hormones; central nervous system and systemic factors, including the aryl hydrocarbon receptor (AhR), play key roles. Understanding these interactions offers new treatment avenues for PCOS and associated conditions.
Area of Science:
- Endocrinology and Neuroscience
- Reproductive Biology
- Metabolic Syndrome Research
Background:
- Traditional PCOS conceptualization focuses on hormonal imbalances and hypothalamic/ovarian dysfunction.
- Emerging evidence highlights significant central nervous system (CNS) and systemic contributions to PCOS pathophysiology.
- Current treatments for PCOS, including oral contraceptives and weight loss, do not fully address underlying mechanisms.
Purpose of the Study:
- To review and integrate data on wider systemic and CNS changes in polycystic ovary syndrome (PCOS).
- To explore the role of night-time cortisol regulation, glucocorticoid receptor (GR) activation, and protective factors.
- To detail the pathophysiological involvement of the aryl hydrocarbon receptor (AhR) and its ligands in PCOS.
Main Methods:
- Review of existing literature on PCOS, focusing on systemic and CNS interactions.
- Analysis of the interplay between the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoid receptor (GR) activation, and cellular regulation.
- Examination of the influence of gut microbiome (butyrate), melatonin pathways, and kynurenine metabolism via AhR.
Main Results:
- Night-time cortisol levels and the cortisol awakening response (CAR) influence GR nuclear translocation, affecting immune and glial cell function.
- Protective factors like butyrate and melatonin inhibit GR translocation, while AhR activation, driven by kynurenine, exacerbates PCOS pathophysiology.
- AhR upregulates the N-acetylserotonin/melatonin ratio, decreasing melatonin and increasing stress plasticity in the paraventricular nucleus.
Conclusions:
- PCOS pathophysiology involves complex interactions between the HPA axis, GR activation, melatonergic pathways, gut microbiome, and AhR signaling.
- These integrated mechanisms explain associations between PCOS and other conditions like depression, diabetes, and autism spectrum disorder.
- Understanding these wider systemic and CNS factors opens new avenues for targeted PCOS research and therapeutic development.
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