Hair cortisol in polycystic ovary syndrome

González, Diego; Maidana, Patricia; Ibar, Carolina; Jamardo, Juan; Jacobsen, Darío; Fritzler, Analy; Fortuna, Federico; Fernández, Gustavo J.; Lamas-Majek, E; Mallea-Gil, Susana; Ballarino, C; Onetto, Claudia; López, Manuel Fernández; Mesch, Viviana; Fabre, Bibiana

doi:10.1038/s41598-022-14061-9

Cited by 4 publications

(2 citation statements)

References 37 publications

(40 reference statements)

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“…This, in addition to the increased in hepatic and adipose expression of Hsd11b1 observed in our mouse study, could contribute to elevated cortisol/corticosterone exposure in patients with PCOS. Indeed, patients with PCOS showed increased hair cortisol concentrations as compared to healthy women [ 51 ], possibly mediated via androgen regulation of HSD11B1 expression.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid Receptor Antagonism Improves Glucose Metabolism in a Mouse Model of Polycystic Ovary Syndrome

Li,

Ying,

Gentenaar

et al. 2023

Journal of the Endocrine Society

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Context Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with obesity, insulin resistance, and dyslipidemia. Hyperandrogenism is a major characteristic of PCOS. Increased androgen exposure is believed to deregulate metabolic processes in various tissues as part of the PCOS pathogenesis, predominantly through the androgen receptor (AR). Notably, various metabolic features in PCOS are similar to those observed after excess glucocorticoid exposure. Objective We hypothesized that glucocorticoid receptor (GR) signaling is involved in the metabolic symptoms of PCOS. Methods In a PCOS model of chronic dihydrotestosterone (DHT) exposure in female mice, we investigated whether GR signaling machinery was (de)regulated, and if treatment with a selective GR antagonist alleviated the metabolic symptoms. Results We observed an upregulation of GR messenger RNA expression in the liver after DHT exposure. In white adipose tissues and liver we found that DHT upregulated Hsd11b1, which encodes for the enzyme that converts inactive into active glucocorticoids. We found that preventive but not therapeutic administration of a GR antagonist alleviated DHT-induced hyperglycemia and restored glucose tolerance. We did not observe strong effects of GR antagonism in DHT-exposed mice on other features like total fat mass and lipid accumulation in various tissues. Conclusion We conclude that GR activation may play a role in glucose metabolism in DHT-exposed mice.

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Section: Discussionmentioning

confidence: 99%

Glucocorticoid Receptor Antagonism Improves Glucose Metabolism in a Mouse Model of Polycystic Ovary Syndrome

Li,

Ying,

Gentenaar

et al. 2023

Journal of the Endocrine Society

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“…PCOS mainly affects the endocrine and reproductive systems, but it may also affect the nervous system, such as the regulation of neurotransmitters, which affects mood and behavior. In addition, the chronic stress state in which PCOS patients live can activate the hypothalamic-pituitary-adrenal (HPA) axis, thus affecting neural signaling [21]. MDD, which is mainly characterized by mood disorders, is nowadays more and more understood as a disorder with an important neurobiological basis.…”

Section: Relationship Between Neuronal Signaling and The Pathogenesis...mentioning

confidence: 99%

Identification of the Shared Gene Signatures and Molecular Mechanisms Between Polycystic Ovarian Syndrome and Major Depressive Disorder: Evidence From Transcriptome Data

Zheng,

Wang,

Liu

2023

Preprint

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Background: Polycystic Ovarian Syndrome (PCOS) is the most common metabolic and endocrine disorder in reproductive-age women, while Major Depressive Disorder (MDD) is a relatively common psychiatric condition. Previous studies have suggested a potential link between PCOS and MDD, but the underlying pathophysiological mechanisms remain unclear. This study aims to identify differential expression genes (DEGs) between PCOS and MDD using bioinformatics methods, explore the associated molecular mechanisms, elucidate the TF-mRNA-miRNA regulatory network involved, predict potential drug molecules, and validate them through molecular docking. Methods: Microarray datasets GSE34526 and GSE125664 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) of PCOS and MDD were analyzed using the GEO2R online tool to obtain shared DEGs to both. Next, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the shared DEGs were performed. Then, protein-protein interaction (PPI) network were constructed and the hub genes were identified using the STRING database and Cytoscape software. Next, NetworkAnalyst was used to construct network between target transcription factors (TFs), microRNAs (miRNAs), and hub genes. Finally, the DSigDB database was used to search for potential drug molecules for the treatment of PCOS combined with MDD, followed by molecular docking using the AutoDock Tools and visualization of the results using PyMol 2.4.0. Results: In the above two datasets, 158 shared DEGs were identified. GO and KEGG enrichment analyses showed that these shared DEGs were mainly enriched in pathways related to neural signaling, energy metabolism, and chronic inflammation with immune dysregulation. In addition, genes with greater than 2-fold median interaction number were further screened by Cytoscape's plugin, cytoNCA, and finally 6 hub genes were selected from the PPI network, ncluding GRIN1, CNR1, DNM1, SYNJ1, PLA2G4A and EPHB2. Then, through the construction of the TF-mRNA-miRNA regulatory network, it was concluded that hsa-miR-27a might be a strongly associated miRNA with the pathogenesis of PCOS and MDD, while TFAP2A might be a strongly associated TF. Finally, orlistat, docosahexaenoic acid (DHA), capsaicin, and myo-inositol were considered as potential drug molecules for the treatment of PCOS combined with MDD using the DSigDB database and related study finding, and then molecular docking was performed using AutoDock Tools. The drug-molecule combination with the lowest binding energy was visualized using PyMol software and it found to be well docked. Conclusions: In summary, we constructed a TF-mRNA-miRNA regulatory network for the first time to characterize the interactions among potential TFs, miRNAs, and hub genes associated with PCOS and MDD, and concluded that aberrant neuronal signaling, disturbed energy metabolism, and immune dysregulation with inflammatory response may be the common pathogenesis of PCOS and MDD. In addition, we identified potential drug molecules for the treatment of PCOS and MDD and performed molecular docking validation. This provides new insights to identify potential associations, potential biomarkers and therapeutic agents for PCOS and MDD.

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Mental Health Across the Menstrual Cycle in Polycystic Ovary Syndrome: Insights and Implications

Phimphasone-Brady,

Ross,

Zhang

et al. 2024

Curr Psychiatry Rep

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Hair cortisol in polycystic ovary syndrome

Cited by 4 publications

References 37 publications

Glucocorticoid Receptor Antagonism Improves Glucose Metabolism in a Mouse Model of Polycystic Ovary Syndrome

Glucocorticoid Receptor Antagonism Improves Glucose Metabolism in a Mouse Model of Polycystic Ovary Syndrome

Identification of the Shared Gene Signatures and Molecular Mechanisms Between Polycystic Ovarian Syndrome and Major Depressive Disorder: Evidence From Transcriptome Data

Mental Health Across the Menstrual Cycle in Polycystic Ovary Syndrome: Insights and Implications

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