Multi-system reproductive metabolic disorder: significance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS)

Li, Yan; Chen, Chang-ye; Ma, Yan; Xiao, Jianru; Luo, Guifang; Li, Yukun; Wu, Daichao

doi:10.1016/j.lfs.2019.04.046

Cited by 129 publications

(115 citation statements)

References 107 publications

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“…There are still several issues to be addressed. Considering that PCOS is a multi-system reproductive metabolic disorder, activation of AMPK signaling may not be the only mechanism responsible for the beneficial effects of BAL [35]. We tried to use dorsomorphin as an AMPK inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Baicalin ameliorates polycystic ovary syndrome through AMP-activated protein kinase

et al. 2019

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Polycystic ovary syndrome (PCOS) is a complex endocrine disorder and regarded as the leading cause of anovulatory infertility. PCOS is characterized by reproductive dysfunction and metabolic disorders. Baicalin (BAL) is one of the most potent bioactive flavonoids isolated from the radix of Scutellaria baicalensis. In the present study, we investigated the potential effects of BAL on PCOS in dehydroepiandrosterone-treated rats. We found that BAL notably reduced the serum levels of free testosterone, total testosterone, follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol in PCOS rats. The increase of serum insulin level and HOMA-IR was markedly inhibited by BAL. Moreover, BAL decreased body weights, increased the number of rats with the regular estrous cycle, and ameliorated ovarian histological changes and follicular development in the DHEA-treated PCOS rats. The increase of pro-inflammatory cytokines (TNFα, IL-1β, and IL-18) and decrease of anti-inflammatory cytokine (IL-10) in PCOS rats were suppressed by BAL. BAL induced a significant decrease in the mRNA expression of steroidogenic enzymes, including 3β-HSD, CYP11A1, CYP19A1, StAR, in ovarian tissues in PCOS rats. Furthermore, BAL inhibited the decrease of AMPK protein level and phosphorylation, the decrease of Akt phosphorylation and the increase of 5α-reductase enzyme 1 expression in ovarian tissues in PCOS rats. The effects of BAL were inhibited by an inhibitor of AMPK, dorsomorphin. The upregulation of AMPK contributed to the beneficial effects of BAL. The results highlight the potential role of BAL for the intervention of PCOS.

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Section: Discussionmentioning

confidence: 99%

Baicalin ameliorates polycystic ovary syndrome through AMP-activated protein kinase

et al. 2019

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“…Female mice with a disruption in the ZFP36L2 gene have disturbed oocyte maturation and ovulation, and its gene product has been implicated in regulation of LHreceptor levels (33,41). There is previous evidence for disruptions in gonadotropin signalling, specifically FSH and LH, being involved in PCOS pathophysiology (8,42). FSH and LH are crucial hormones for follicular development and ovulation (5,6,8), The two hormones share an alpha chain (encoded by CGA (33)), and disruption of FSHB has been associated with higher LH levels in both humans and mice (43,44).…”

Section: Discussionmentioning

confidence: 98%

“…There is previous evidence for disruptions in gonadotropin signalling, specifically FSH and LH, being involved in PCOS pathophysiology (8,42). FSH and LH are crucial hormones for follicular development and ovulation (5,6,8), The two hormones share an alpha chain (encoded by CGA (33)), and disruption of FSHB has been associated with higher LH levels in both humans and mice (43,44). SNPs in the FSHB region have also been associated with levels of both LH and LH/FSH (45)(46)(47).…”

Section: Discussionmentioning

confidence: 98%

“…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%

“…hyperandrogenism and disturbances in follicular maturation and ovulation (3,12). Other possible contributing factors that have been suggested include for example insulin resistance and inflammation (3,8). There is also evidence for a strong genetic component, with genetic factors suggested to explain 66% of the disease variance (13).…”

Section: Introductionmentioning

confidence: 99%

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

Censin

Bovijn

Holmes

et al. 2020

Preprint

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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.

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Association Between Insulin Resistance Indices and Liver Function Parameters Among Women With Polycystic Ovary Syndrome

Saei Ghare Naz,

Mousavi,

Firouzi

et al. 2024

Endocrino Diabet & Metabol

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ObjectiveThis study aimed to investigate whether polycystic ovary syndrome (PCOS) status changes the association between insulin resistance (IR) indices and liver function parameters among women.MethodsThis is a cross‐sectional, population‐based study. We selected 1101 subjects aged ≥20 years from participants of Tehran Lipid and Glucose Study (TLGS). All of them had known the status of PCOS, and all variables were related to the IR indices and liver function parameters. The main outcome measures were TG/HDL‐C and triglyceride‐glucose (TyG) and liver function parameters (hepatic steatosis index [HSI], alanine transaminase [ALT] and aspartate transaminase [AST]).ResultIn the present study, there was no significant difference between the PCOS and the non‐PCOS regarding the presence of liver function abnormalities. A model adjusted by age and BMI showed that the upper tertile of TyG index was positively associated with high AST (OR = 3.04 [95% CI: 1.20–7.68], p < 0.05), high ALT (4.76 [3.07–7.36], p < 0.05) and high HSI (8.44 [1.82–39.17], p < 0.05). Although the history of diabetes had a positive impact on elevated AST (1.66 [1.15, 2.40], p < 0.05), the third tertile of TG/HDL‐C was associated with increased odds of elevated ALT (3.35 [2.21–5.06]) and HSI (6.55 [1.17–36.46]), whereas the second tertile of TG/HDL‐C (OR = 2.65, CI 95%: 1.74–4.03) was also positively associated with elevated ALT. PCOS had no significant association with elevated liver function tests.ConclusionThe highest tertile of TyG index and the TG/HDL‐C ratio as a surrogate of IR might play a role in detecting abnormalities of liver function parameters among women. However, PCOS status cannot change the association between IR and liver dysfunction.

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Multi-system reproductive metabolic disorder: significance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS)

Cited by 129 publications

References 107 publications

Baicalin ameliorates polycystic ovary syndrome through AMP-activated protein kinase

Baicalin ameliorates polycystic ovary syndrome through AMP-activated protein kinase

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

Association Between Insulin Resistance Indices and Liver Function Parameters Among Women With Polycystic Ovary Syndrome

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