Soy isoflavones exert beneficial effects on letrozole-induced rat polycystic ovary syndrome (PCOS) model through anti-androgenic mechanism

Rajan, Ravi Kumar; Kumar, Madhu; Bhaskar, B.

doi:10.1080/13880209.2016.1258425

Cited by 127 publications

(100 citation statements)

References 35 publications

(36 reference statements)

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“…Moreover, although testosterone, DHT and letrozole are commonly employed to induce PCOS-like characteristics in pubertal or adult female rodents, it is not well understood whether androgen excess during these time periods results in organizational or activational effects. Indeed, several recent studies have assumed that letrozole treatment of pubertal female rodents causes organizational effects [47][48][49][50]. Given that our study demonstrated that letrozole treatment exerted mostly activational effects during puberty, this finding implies that letrozole treatment needs to be present for the entire duration of the study to effectively model PCOS.…”

Section: Discussionsupporting

confidence: 58%

Letrozole treatment of pubertal female mice results in activational effects on reproduction, metabolism and the gut microbiome

Arroyo

et al. 2019

PLoS ONE

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Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women that is comprised of two out of the following three features: hyperandrogenism, oligo-or amenorrhea, or polycystic ovaries. In addition to infertility, many women with PCOS have metabolic dysregulation that increases the risk of developing type 2 diabetes, hypertension, and non-alcoholic fatty liver disease. Changes in the gut microbiome are associated with PCOS and gut microbes may be involved in the pathology of this disorder. Since PCOS often manifests in the early reproductive years, puberty is considered to be a critical time period for the development of PCOS. Exposure to sex steroid hormones during development results in permanent, organizational effects, while activational effects are transient and require the continued presence of the hormone. Androgens exert organizational effects during prenatal or early post-natal development, but it is unclear whether androgen excess results in organizational or activational effects during puberty. We recently developed a letrozole-induced PCOS mouse model that recapitulates both reproductive and metabolic phenotypes of PCOS. In this study, we investigated whether letrozole treatment of pubertal female mice exerts organizational or activational effects on host physiology and the gut microbiome. Two months after letrozole removal, we observed recovery of reproductive and metabolic parameters, as well as diversity and composition of the gut microbiome, indicating that letrozole treatment of female mice during puberty resulted in predominantly activational effects. These results suggest that if exposure to excess androgens during puberty leads to the development of PCOS, reduction of androgen levels during this time may improve reproductive and metabolic phenotypes in women with PCOS. These results also imply that continuous letrozole exposure is required to model PCOS in pubertal female mice since letrozole exerts activational rather than organizational effects during puberty.

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Section: Discussionsupporting

confidence: 58%

Letrozole treatment of pubertal female mice results in activational effects on reproduction, metabolism and the gut microbiome

Arroyo

et al. 2019

PLoS ONE

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“…This excessive testosterone cause other problematic issues like acne, hirsutism and hair loss and also inhibits normal ovulation. So, reducing testosterone to the normal healthy level is the prime goal of PCOS treatment.And our study found statistically significant decrease in testosterone values in all treatment levels as 97.34 ± 3.03 (ng/dl) in SIF 0.10 , 89.29 ± 2.71 (ng/dl) in SIF 0.15 and 79.61 ± 2.85 (ng/dl) in SIF 0.20 [25,26]. found similar results on decrease in testosterone levels by using different dosage levels of soy isoflavones for different time periods.…”

supporting

confidence: 61%

Phytoestrogenic Effects of Various Levels of Soy Isoflavones in Polycystic Ovarian Syndrome

Mazhar

Nisa

Arshad

2020

Preprint

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Background: Soy isoflavones (SI) has estrogenic effect in tissues by binding to estrogen receptors and might be beneficial for women with Polycystic Ovarian Syndrome (PCOS) by reduction in testosterone, cholesterol , Insulin , weight gain, inflammatory markers and oxidative stress. Methods: The study was plane to examine the effect of various levels of SI on nutrient intake, digestibility, lipid profile, insulin and reproductive hormones of estradiol-valerate (4mg/rat/IM) PCOS induced rat models. Thirty-Six Wistar 45 days old rats weighing 95 ± 5g were divided into 4 groups, each having 9 rats: C (control: without SF), SF10 (SF 0.10g/Kg BW), SF15 (SF 0.15g/Kg BW) and SF20 (SF 0.20g/Kg BW). SF was given through the oral gavage. Food and water were offered ad libitum and intake was recorded daily. Body weight was recorded on weekly basis. During last week of trial, collected feces by total collection method and blood samples were used to calculate nutrient digestibility and biochemical analysis respectively. The Completely Randomized Design and LSD test were used to analyze the data. Results: The significant results were observed in female rats fed SF10, SF15 and SF20 compared to C. Estrogen, progesterone and prolactin were (P<0.05) high in rats fed SF diet that was 4 and 30% increase from C respectively. Insulin, Testosterone, FSH and LH were lowest in rats fed diet SF20. Significant (P<0.05) reduction in cholesterol was observed in rats fed SF15 and SF20 as compared to C. Serum HDL was improved (P<0.05) in all SIF 0.10 , SIF 0.15 and SIF 0.20 as 26.88±1.59 (mg/dl), 32.40±1.42 (mg/dl) and 53.44±1.50 (mg/dl) in comparison to PC. Serum LDL was significantly reduced to 68.89±4.36 (mg/dl) in SIF 0.20 , and to 108.20±4.14 (mg/dl) in SIF 0.15 whereas, insignificant reduction was observed in SIF 0.10 (127.75±4.62 mg/dl) as compared to PC. Highly significant reduction was noted in triglycerides level in SIF 0.20 as 115.00±2.04 (mg/dl), however, significant reduction was observed in both SIF 0.10 and SIF 0.15 as compared to PC after three months of treatment with soy isoflavones.Conclusions: It is concluded that soy isoflavones have potential role on reproductive hormones, insulin levels, weight, lipid profile and nutrient digestibility in PCOS induced rats.

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“…The structure of daid is similar to 17β-estradiol, which can bind to estrogen receptors (ER) and modulate the cell cycle, survival and apoptosis [34,35]. GBM expresses both ERα and ERβ [36][37][38].…”

Section: Discussionmentioning

confidence: 99%

“…Those signaling pathways induced by moesin phosphorylation needs to be further studied. Even though ERM proteins play important roles in cell division [34][35][36][37]. the specific regulation of moesin on β-catenin-induced cell cycle arrest is worth investigating.…”

Section: Discussionmentioning

confidence: 99%

Daidzein derivative daid002 inhibits glioblastoma growth via disrupting the interaction between moesin and CD44

Zhang¹,

Liu²,

Zhang³

et al. 2018

Oncotarget

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Glioblastoma multiforme is a fatal brain tumor with very limited therapeutic options. Recently, an ezrin-radixin-moesin family protein, moesin, is reported to be positively correlated with higher grade of glioblastoma. Here, we reported that daid002, a novel daidzein derivative, inhibited glioblastoma growth and induced G0/ G1 phase arrest. Daid002 decreased moesin phosphorylation through restraint of the direct interaction between moesin and CD44 on the cell membrane and reduced cyclin D1 expression via regulating nuclear translocation of β-catenin. In vivo, daid002 exerted a significant inhibition on glioblastoma growth through CD44/moesin signaling. Our findings established daid002 as an anti-glioblastoma agent by targeting CD44/moesin.

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Soy isoflavones exert beneficial effects on letrozole-induced rat polycystic ovary syndrome (PCOS) model through anti-androgenic mechanism

Cited by 127 publications

References 35 publications

Letrozole treatment of pubertal female mice results in activational effects on reproduction, metabolism and the gut microbiome

Letrozole treatment of pubertal female mice results in activational effects on reproduction, metabolism and the gut microbiome

Phytoestrogenic Effects of Various Levels of Soy Isoflavones in Polycystic Ovarian Syndrome

Daidzein derivative daid002 inhibits glioblastoma growth via disrupting the interaction between moesin and CD44

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