Hormonal alterations in PCOS and its influence on bone metabolism

Krishnan, Abhaya; Muthusami, Sridhar

doi:10.1530/joe-16-0405

Cited by 125 publications

(99 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly, in organismal system pathway, osteoclast differentiation and chemokine signaling (hsa04380 and hsa04062 respectively); apoptosis (hsa04210) under cellular processes; PI3K-Akt signaling pathway (hsa04151) under environment information processing; and protein-processing in endoplasmic reticulum (hsa04141) under genetic information processing class were highly enriched. The results are in line with the findings where involvement of cancer(Dumesic & Lobo, 2013), osteoclast differentiation(Krishnan & Muthusami, 2017), apoptosis(Yan et al, 2012) and PI3k -Akt signaling pathway(Li et al, 2017) are found to be in close relationship with PCOS. The anti-PCOS effects of T. purpurea can be directly linked to these proteins through the protein targeting capability of its DPCs.To elucidate the cellular, molecular and biological level effects of T. purpurea, protein targets of this plant were subjected to gene ontology enrichment analysis.…”

supporting

confidence: 91%

Deciphering the multi-scale mechanisms ofTephrosia purpureaagainst polycystic ovarian syndrome (PCOS) and its major psychiatric comorbidities: studies from network-pharmacological perspective

Choudhary

Singh

2019

Preprint

View full text Add to dashboard Cite

Tephrosia purpurea (T. purpurea), a plant belonging to Fabaceae (pea) family, is a well-known Ayurvedic herb and is commonly known as Sarapunkha in traditional Indian medicinal system. Described as "Sarwa wranvishapaka", i.e. having capability to heal all types of wounds, it is particularly recognized for its usage in splenomegaly. Towards exploring the comprehensive effects of T. purpurea against polycystic ovarian syndrome (PCOS), its phytochemicals were extensively reviewed and their network pharmacology evaluation is carried out in this study. The complex regulatory potential of its 76 phytochemicals (PCs) against PCOS are enquired by developing and analyzing high confidence tripartite networks of protein targets of each phytochemical at both pathway and disease association scales. We also developed a highconfidence human PPI sub-network specific to PCOS, explored its modular architecture and probed the drug-like phytochemicals (DPCs) having multi-module regulatory potential. The proteins belonging to endocrine system were identified as major targets of the PCs. The study reports 30 DPCs based on ADMET and drug-like properties. Multi-targeting and synergistic capacities of the 12 DPCs against 10 protein targets were identified and evaluated using molecular docking and interaction analyses. The study concludes by highlighting a couple of DPCs as potential sources of PCOS regulators.

show abstract

supporting

confidence: 91%

Deciphering the multi-scale mechanisms ofTephrosia purpureaagainst polycystic ovarian syndrome (PCOS) and its major psychiatric comorbidities: studies from network-pharmacological perspective

Choudhary

Singh

2019

Preprint

View full text Add to dashboard Cite

show abstract

“…The etiological factors for the onset of PCOS include epigenetic modifications, lifestyle, and environmental exposure to xenoestrogens/xenoandrogens. A previous review published from our laboratory revealed the link between various endocrine changes and its relevance to bone function in PCOS [5]. Polycystic ovary morphology (PCOM) is a well-established feature of PCOS-like phenotype, as PCOS is based on ovarian morphological changes associated with increased ovarian volume, ovarian area, hyperandrogenism and anovulation that collectively leading to reprogramming of hypothalamic-pituitary-ovarian axis [4,6].…”

Section: Introductionmentioning

confidence: 99%

Effect of DHT-Induced Hyperandrogenism on the Pro-Inflammatory Cytokines in a Rat Model of Polycystic Ovary Morphology

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background and Objectives: Polycystic ovary syndrome (PCOS) is one of the most prevalent disorders among women of reproductive age. It is considered as a pro-inflammatory state with chronic low-grade inflammation, one of the key factors contributing to the pathogenesis of this disorder. Polycystic ovary is a well-established criterion for PCOS. The present investigation aimed at finding the role of hyperandrogenism, the most important feature of PCOS, in the development of this inflammatory state. To address this problem, we adopted a model system that developed polycystic ovary morphology (PCOM), which could be most effectively used in order to study the role of non-aromatizable androgen in inflammation in PCOS. Materials and Methods: Six rats were used to induce PCOM in 21-days-old female Wistar albino rats by using a pre-determined release of dihydrotestosterone (DHT), a potent non-aromatizable androgen, achieved by implanting a DHT osmotic pump, which is designed to release a daily dose of 83 μg. Results: After 90 days, the rats displayed irregular estrous cycles and multiple ovarian cysts similar to human PCOS. Elevated serum inflammatory markers such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and the presence of a necrotic lesion in the liver, osteoclast in the femur, multinucleated giant cells and lymphocytes in the ovary based on histopathological observation of DHT-treated rats clearly indicated the onset of inflammation in the hyperandrogenic state. Our results show no significant alterations in serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), insulin, and cortisol between control and hyperandrogenised rats. DHT was significantly elevated as compared to control. mRNA studies showed an increased expression level of TNF-α and IL-1β, further, the mRNA expression of urocortin 1 (Ucn-1) was stupendously elevated in the liver of hyperandrogenised rats. Conclusions: Thus, results from this study provide: (1) a good PCOM model system in order to study the inflammatory changes in PCOS aspects, (2) alteration of inflammatory markers in PCOM rats that could be either due to its direct effect or by the regulation of various inflammatory genes and markers in the liver of hyperandrogenic state suggesting the regulatory role of DHT, and (3) alteration in stress-related protein in the liver of PCOM rats.

show abstract

“…In healthy women of reproductive age, the pituitary gland secretes the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in response to pulsatile secretion of gonadotropin releasing hormone (GnRH) (5,6). These GnRH pulses are more frequent in women with PCOS (3,7). This changed secretion pattern causes an imbalance between LH and FSH, and a higher LH/FSH ratio (3,(7)(8)(9)(10)(11), which may contribute to e.g.…”

Section: Introductionmentioning

confidence: 99%

“…These GnRH pulses are more frequent in women with PCOS (3,7). This changed secretion pattern causes an imbalance between LH and FSH, and a higher LH/FSH ratio (3,(7)(8)(9)(10)(11), which may contribute to e.g. hyperandrogenism and disturbances in follicular maturation and ovulation (3,12).…”

Section: Introductionmentioning

confidence: 99%

Colocalization highlights genes in hypothalamic–pituitary–gonadal axis as potentially mediating polycystic ovary syndrome risk

Censin

Bovijn

Holmes

et al. 2020

Preprint

View full text Add to dashboard Cite

Polycystic ovary syndrome (PCOS) is a common disease in women with consequences for reproductive, metabolic and psychological health. Women with PCOS have disrupted signalling in the hypothalamic-pituitary-gonadal axis and studies have indicated that the disease has a large genetic component. While a recent genome-wide association study of PCOS performed in up to 10,074 cases and 103,164 controls of European decent identified 14 PCOS-associated regions, much of the disease pathophysiology remains unclear.Here, we use a Bayesian colocalization approach to highlight genes that may have a potential role in PCOS pathophysiology and thus are of particular interest for further functional follow-up. We evaluated the posterior probabilities of shared causal variants between PCOS genetic risk loci and intermediate cellular phenotypes in one protein and two expression quantitative trait locus datasets, respectively. Sample sizes ranged from 80 to 31,684. In total, we identified seven proteins or genes with evidence of a shared causal variant for almost a third of PCOS signals, including follicle stimulating hormone (FSH) and the genes ERBB3, IKZF4, RPS26, SUOX, ZFP36L2, and C8orf49. Several of these genes and proteins have been implicated in the hypothalamic-pituitary-gonadal signalling pathway.In summary, our results suggest potential effector proteins and genes for PCOS association signals. This highlights genes for functional follow-up in order to demonstrate a causal role in PCOS pathophysiology.

show abstract

Hormonal alterations in PCOS and its influence on bone metabolism

Cited by 125 publications

References 66 publications

Deciphering the multi-scale mechanisms ofTephrosia purpureaagainst polycystic ovarian syndrome (PCOS) and its major psychiatric comorbidities: studies from network-pharmacological perspective

Deciphering the multi-scale mechanisms ofTephrosia purpureaagainst polycystic ovarian syndrome (PCOS) and its major psychiatric comorbidities: studies from network-pharmacological perspective

Effect of DHT-Induced Hyperandrogenism on the Pro-Inflammatory Cytokines in a Rat Model of Polycystic Ovary Morphology

Colocalization highlights genes in hypothalamic–pituitary–gonadal axis as potentially mediating polycystic ovary syndrome risk

Contact Info

Product

Resources

About