scholarly journals The Mechanism of Androgen Actions in PCOS Etiology

2019 ◽  
Vol 7 (9) ◽  
pp. 89 ◽  
Author(s):  
Valentina Rodriguez Paris ◽  
Michael J. Bertoldo
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Future Development ◽  
Molecular Mechanisms ◽  
Ad Hoc ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Female Fertility ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
The Future

Polycystic ovary syndrome (PCOS) is the most common endocrine condition in reproductive-age women. By comprising reproductive, endocrine, metabolic and psychological features—the cause of PCOS is still unknown. Consequently, there is no cure, and management is persistently suboptimal as it depends on the ad hoc management of symptoms only. Recently it has been revealed that androgens have an important role in regulating female fertility. Androgen actions are facilitated via the androgen receptor (AR) and transgenic Ar knockout mouse models have established that AR-mediated androgen actions have a part in regulating female fertility and ovarian function. Considerable evidence from human and animal studies currently reinforces the hypothesis that androgens in excess, working via the AR, play a key role in the origins of polycystic ovary syndrome (PCOS). Identifying and confirming the locations of AR-mediated actions and the molecular mechanisms involved in the development of PCOS is critical to provide the knowledge required for the future development of innovative, mechanism-based interventions for the treatment of PCOS. This review summarises fundamental scientific discoveries that have improved our knowledge of androgen actions in PCOS etiology and how this may form the future development of effective methods to reduce symptoms in patients with PCOS.

scholarly journals Differential expression of long non-coding RNA Regulator of reprogramming and its molecular mechanisms in polycystic ovary syndrome

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Zhihong Zhang ◽  
Min Sang ◽  
Siqin Liu ◽  
Jing Shao ◽  
Yunjiang Cai
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Polycystic Ovary ◽  
Pearson Correlation ◽  
Reproductive Age ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Control Group ◽  
Ovary Syndrome ◽  
Gene Assay

Abstract Background Polycystic ovary syndrome (PCOS) is a common endocrine disease in women of reproductive age. Multiple studies have shown that long non-coding RNAs (lncRNA) and microRNAs (miRNA) play a role in PCOS. This study aimed to explore the role and molecular mechanism of lncRNA -Regulator of reprogramming (lncROR) in PCOS. Results Expression level of lncROR in PCOS patients was up-regulated, while level of miR-206 was down-regulated in comparison with control group (P < 0.001). Logistics regression analysis showed that lncROR and miR-206 were independent predictors of PCOS. The ROC curve showed that lncROR had a high diagnostic value for PCOS with an AUC value of 0.893. Pearson correlation coefficient indicated that the expression level of miR-206 was negatively correlated with the level of lncROR. CCK-8 assay and apoptosis assay revealed that downregulation of lncROR up-regulated the expression of miR-206, thereby inhibiting cell proliferation and promoting cell apoptosis. However, silencing the expression of miR-206 reversed the above effects caused by down-regulation of lncROR expression. Luciferase reporter gene assay suggested that there was a target relationship between lncROR and miR-206. VEGF was proved to be the target gene of miR-206. Conclusions Highly expressed lncROR indirectly up-regulated the expression of VEGF by down-regulating the expression of miR-206, thereby promoting the proliferation of KGN cells and inhibiting apoptosis, and further promoting the development of PCOS.

scholarly journals Androgens and ovarian function: translation from basic discovery research to clinical impact

2019 ◽  
Vol 242 (2) ◽  
pp. R23-R50 ◽  
Author(s):  
K A Walters ◽  
V Rodriguez Paris ◽  
A Aflatounian ◽  
D J Handelsman
Keyword(s):  
Future Development ◽  
Molecular Mechanisms ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Reproductive Function ◽  
Poor Responders ◽  
Discovery Research ◽  
The Future ◽  
The Impact

In the last decade, it has been revealed that androgens play a direct and important role in regulating female reproductive function. Androgens mediate their actions via the androgen receptor (AR), and global and cell-specific Ar-knockout mouse models have confirmed that AR-mediated androgen actions play a role in regulating female fertility and follicle health, development and ovulation. This knowledge, along with the clinical data reporting a beneficial effect of androgens or androgen-modulating agents in augmenting in vitro fertilization (IVF) stimulation in women termed poor responders, has supported the adoption of this concept in many IVF clinics worldwide. On the other hand, substantial evidence from human and animal studies now supports the hypothesis that androgens in excess, acting via the AR, play a key role in the origins of polycystic ovary syndrome (PCOS). The identification of the target sites of these AR actions and the molecular mechanisms involved in underpinning the development of PCOS is essential to provide the knowledge required for the future development of novel, mechanism-based therapies for the treatment of PCOS. This review will summarize the basic scientific discoveries that have enhanced our knowledge of the roles of androgens in female reproductive function, discuss the impact these findings have had in the clinic and how a greater understanding of the role androgens play in female physiology may shape the future development of effective strategies to improve IVF outcomes in poor responders and the amelioration of symptoms in patients with PCOS.

scholarly journals Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome

2010 ◽  
Vol 162 (2) ◽  
pp. 193-212 ◽  
Author(s):  
Evanthia Diamanti-Kandarakis ◽  
Charikleia D Christakou ◽  
Eleni Kandaraki ◽  
Frangiskos N Economou
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Unknown Etiology ◽  
Ovary Syndrome ◽  
Therapeutic Implications ◽  
Therapeutic Benefits ◽  
Insulin Sensitizers ◽  
Promising Area

AbstractPolycystic ovary syndrome (PCOS) is now recognized to be the most common endocrinopathy in women of reproductive age with a prevalence of 6.6–6.8%. PCOS, a syndrome of unknown etiology, was initially regarded as a reproductive disorder. However, in the last 15 years the role of insulin resistance (IR) has been identified as a significant contributor to the pathogenesis of PCOS, and the metabolic and cardiovascular sequelae of the syndrome have been increasingly appreciated. The coexistence and interaction of reproductive and cardiometabolic abnormalities in the context of PCOS have created a need for a modified therapeutic management of affected women.Insulin sensitizers, particularly metformin, have been introduced as a pharmaceutical option targeting not only IR, but several other aspects of the syndrome, including reproductive abnormalities. The landscape of the multifaceted actions of metformin evolves to broaden the therapeutic implications of this old drug in a new fashion for patients with PCOS. Most recently, the spectrum of metformin's targets has been expanded, and molecular studies have explored the tissue-specific mechanisms of metformin in the liver, the muscle, the endothelium, and the ovary. The use of metformin in pregnant women with PCOS comprises another scarcely explored, but promising area of research. This review attempts to cover the spectrum of metformin's cellular actions in different tissues and to summarize the current literature regarding the potential medical value of this medication in PCOS. Even if many of these actions are individually modest, they seem to be collectively sufficient to confer therapeutic benefits not only in cardiometabolic aspects but also in reproductive aspects of PCOS.

Polycystic ovary syndrome and probiotics: a natural approach to an inflammatory disease

2020 ◽  
Vol 16 ◽  
Author(s):  
Antonio Schiattarella ◽  
Gaetano Riemma ◽  
Marco La Verde ◽  
Gianluigi Franci ◽  
Annalisa Chianese ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Critical Role ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Natural Approach ◽  
New Treatment ◽  
Gut Microbial Community ◽  
New Evidence

: Polycystic ovary syndrome (PCOS) is a condition that affects about 15% of women of reproductive age and is correlated with infertility, insulin resistance, and obesity. The etiology of PCOS is multifactorial and genetic, endocrine, and metabolic causes were involved. New evidence suggests a link between microorganisms residing in the digestive tracts of humans and the development of PCOS. Moreover, an imbalance in the gut microbial community could be a possible factor for the onset of insulin resistance and obesity. Hyperandrogenism, a key feature of PCOS, could also play a critical role in shaping the microbiome community. Probiotics could modify the gut microbiota and serve as a potential treatment for PCOS. Here we disclose the association between PCOS and intestinal microbiota and the possible role of probiotics as a new treatment approach.

scholarly journals Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

2019 ◽  
Vol 104 (11) ◽  
pp. 5372-5381 ◽  
Author(s):  
Nigel K Stepto ◽  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Kirsty A Walters ◽  
Raymond J Rodgers
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Basic Research ◽  
Future Research ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

Health Care-Related Economic Burden of Polycystic Ovary Syndrome in the United States: Pregnancy-Related and Long-Term Health Consequences

2021 ◽  
Author(s):  
Carrie Riestenberg ◽  
Anika Jagasia ◽  
Daniela Markovic ◽  
Richard P Buyalos ◽  
Ricardo Azziz
Keyword(s):  
United States ◽  
Polycystic Ovary Syndrome ◽  
Economic Burden ◽  
Polycystic Ovary ◽  
The United States ◽  
Reproductive Age ◽  
Cochrane Library ◽  
Control Group ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive-aged women, affecting approximately 5-20% of women of reproductive age. A previous estimate noted that the economic burden of PCOS approximates $3.7 billion annually in 2020 USD when considering only the costs of the initial diagnosis and of reproductive endocrine morbidities, not considering the costs of pregnancy-related and long-term morbidities. Objective To estimate the excess prevalence and economic burden of pregnancy-related and long-term health morbidities attributable to PCOS. Data Sources PubMed, EmBase and Cochrane Library. Study Selection Studies in which the diagnosis of PCOS was consistent with the Rotterdam, National Institutes of Health (NIH), or Androgen Excess & PCOS (AE-PCOS) Society criteria, or that used electronic medical record diagnosis codes, or diagnosis based on histopathologic sampling were eligible for inclusion. Studies that included an outcome of interest and a control group of non-PCOS patients who were matched or controlled for body mass index (BMI) were included. Data Extraction Two investigators working independently extracted data on study characteristics and outcomes. Data Synthesis Data was pooled using random-effects meta-analysis. The I 2statistic was used to assess inter-study heterogeneity. The quality of selected studies was assessed using the Newcastle-Ottawa Scale. Results The additional total healthcare-related economic burden due to pregnancy-related and long-term morbidities associated with PCOS in the United States is estimated to be $4.3 billion annually in 2020 USD. Conclusions Together with our prior analysis, the economic burden of PCOS is estimated at $8 billion annually in 2020 USD.

Disorders of steroid metabolism in women of reproductive age with polycystic ovary syndrome

2021 ◽  
Author(s):  
Olga Glavnova ◽  
Ludmila Velikanova ◽  
Natalia Vorokhobina ◽  
raviliy Galakhova ◽  
Ekaterina Malevanania ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Steroid Metabolism ◽  
Women Of Reproductive Age ◽  
Ovary Syndrome
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