Dulaglutide, a long-acting GLP-1 receptor agonist, can improve hyperandrogenemia and ovarian function in DHEA-induced PCOS rats

Wu, Luming; Wang, Yin-Xue; Zhan, Yue; Liu, A-hui; Wang, Yixiang; Shen, Haofei; Wang, Yifan; Wang, Liyan; Tao, Zhongbin; Wang, Yiqing

doi:10.1016/j.peptides.2021.170624

Cited by 17 publications

(8 citation statements)

References 48 publications

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“…91 At the same time, animal experiments by Wu et al confirmed that rat serum androgen levels were significantly reduced and SHBG content was significantly increased in the groups treated with three different doses of dulaglutide compared with that in the PCOS group induced by DHEA. 92 In addition, in our previous animal experiments, we found that both MET and exenatide can alleviate glucose and lipid metabolism disorders and hyperandrogenemia and increase the serum SHBG level in a PCOS rat model induced by letrozole combined with an HFD. Interestingly, our results also emphasized that compared with MET, exenatide can have stronger effects on regulating the PI3K/AKT pathway, reducing liver TG deposition, and upregulating the expression levels of SHBG and HNF-4α in the liver tissue of PCOS-with-IR rats.…”

Section: Glucagon-like Peptide-1 Receptor Agonists (Glp-1 Ras)mentioning

confidence: 79%

Effect of Sex Hormone-Binding Globulin on Polycystic Ovary Syndrome: Mechanisms, Manifestations, Genetics, and Treatment

Xing¹,

Zhang²,

Zhao³

et al. 2022

IJWH

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Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases causing infertility in women of childbearing age. It is characterized by hyperandrogenemia (HA), chronic anovulation, and polycystic ovary morphology (PCOM). Most women with PCOS have metabolic abnormalities. Sex hormone-binding globulin (SHBG), a transport carrier that binds estrogen and androgens and regulates their biological activity, is usually used as an indicator of hyperandrogenism in women with PCOS. Low serum SHBG levels are considered a biomarker of metabolic abnormalities and are associated with insulin resistance (IR), HA, and abnormal glucose and lipid metabolism in PCOS patients. SHBG is also related to the long-term prognosis of PCOS, whereas SHBG gene polymorphism is associated with PCOS risk. In addition, the administration of metformin (MET), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), thiazolidinediones (TZDs), compound oral contraceptives (COCs), as well as nutrient supplements such as inositol (MI), vitamin D, and synbiotics can regulate SHBG levels to ameliorate PCOS complications and improve prognosis. This review focuses on the interaction between SHBG and various PCOS complications as well as the regulation of SHBG by various drugs and nutrients and its therapeutic effects on PCOS.

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Section: Glucagon-like Peptide-1 Receptor Agonists (Glp-1 Ras)mentioning

confidence: 79%

Effect of Sex Hormone-Binding Globulin on Polycystic Ovary Syndrome: Mechanisms, Manifestations, Genetics, and Treatment

Xing¹,

Zhang²,

Zhao³

et al. 2022

IJWH

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“…The number of cystic follicles was increased in PCOS ovarian tissues while the corpus luteum was reduced (Wang et al, 2021), which is similar to our results. Although DHEA induced PCOS model is not the most ideal model, it is currently a widely used model with clinically similar phenotypes (Joseph Igbo, 2022; Wu et al, 2021). In this study, the estrous cycle disorders, increased T, LH, FSH, and LH/FSH levels in serum, increased cystic follicles and corpus luteum in ovarian tissues were indicated the successful establishment of the PCOS rat model.…”

Section: Discussionmentioning

confidence: 99%

CPEB1 induces autophagy and promotes apoptosis in ovarian granulosa cells of polycystic ovary syndrome

Xuan,

Ren,

et al. 2024

Molecular Reproduction Devel

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Inflammatory damage in ovarian granulosa cells (GCs) is a key mechanism in polycystic ovary syndrome (PCOS), cytoplasmic polyadenylation element binding protein‐1 (CPEB1) is important in inflammatory regulation, however, its role in PCOS is unclear. We aim to research the mechanism of CPEB1 in ovarian GCs in PCOS using dehydroepiandrosterone (DHEA)‐induced PCOS rat models and testosterone‐incubated GC models. The pathophysiology in PCOS rats was analyzed. Quantitative‐realtime‐PCR, TUNEL, immunohistochemistry, and Western blot were applied for quantification. Additionally, cell counting kit‐8, flow cytometry, immunofluorescence, Western blot, and Monodansylcadaverine staining were performed. We found that PCOS rat models exhibited a disrupted estrus cycle, elevated serum levels of testosterone, luteinizing hormone (LH), and follicle‐stimulating hormone (FSH), increased LH/FSH ratio, and heightened ovarian index. Furthermore, reduced corpus luteum and increased follicular cysts were observed in ovarian tissue. In ovarian tissue, autophagy and apoptosis were activated and CPEB1 was overexpressed. In vitro, CPEB1 overexpression inhibited cell viability and sirtuin‐1 (SIRT1), activated tumor necrosis factor‐α, and interleukin‐6 levels, as well as apoptosis and autophagy; however, CPEB1 knockdown had the opposite effect. In conclusion, overexpression of CPEB1 activated autophagy and apoptosis of ovarian GCs in PCOS.

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“…Previous studies have demonstrated that the DHEA-induced rat model in PCOS displays the clinical characteristics of PCOS in humans, including hyperandrogenism, obesity, and pathological morphology of polycystic ovary [ 24 ]. Yu et al indicated that decreased endometrial receptivity and abnormal ovarian morphology existed in mice exposed by DHEA [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Acupuncture Improves Endometrial Angiogenesis by Activating PI3K/AKT Pathway in a Rat Model with PCOS

Xing

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Acupuncture, a treatment derived from traditional Chinese medicine, can effectively relieve the symptoms and improve pregnancy outcome in patients with polycystic ovary syndrome (PCOS); however, its mechanism remains unclear. This study aimed at investigating whether acupuncture could improve endometrial angiogenesis and thus endometrial receptivity via activating PI3K/AKT pathway in PCOS rats. Methods. We established a rat model with PCOS, which was induced by DHEA. Acupuncture was performed every other day for 15 days, and the PI3K inhibitor (LY294002) was intraperitoneal injected 30 mins before acupuncture treatment. Females rats were mated with male SPF SD rats in a ratio of 2 : 1 after treatment and sacrificed on the 5th day when the vaginal plug was identified. The number of implantation sites was observed, followed by ovarian and endometrial morphology detected with hematoxylin-eosin staining and a scanning electron microscope, estrous cycle detected with vaginal smear analysis, and sex hormones and angiogenesis-related PI3K/AKT gene/protein expression detected with enzyme-linked immunosorbent assay, western blotting, immune histochemistry, and quantitative real-time PCR. Results. Acupuncture notably improved implantation sites’ number, endometrial receptivity factors including endometrial morphology, pinopodes, HOX-10, and LIF protein expression, as well as angiogenesis and PI3K/AKT pathway factors such as VEGF, VEGFR2, Ang-1, PI3K, AKT, and P-AKT gene/protein expression and the level of eNOS and NO in the endometrium of rats with PCOS; PCOS-like symptoms were alleviated as well. The efficacy of acupuncture on a rat model with PCOS was counteracted by the combination with the PI3K inhibitor. Conclusion. Acupuncture improves endometrial angiogenesis by activating the PI3K/AKT pathway, thus promoting endometrial receptivity and the number of implantation sites in rats with PCOS.

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Dulaglutide, a long-acting GLP-1 receptor agonist, can improve hyperandrogenemia and ovarian function in DHEA-induced PCOS rats

Cited by 17 publications

References 48 publications

Effect of Sex Hormone-Binding Globulin on Polycystic Ovary Syndrome: Mechanisms, Manifestations, Genetics, and Treatment

Effect of Sex Hormone-Binding Globulin on Polycystic Ovary Syndrome: Mechanisms, Manifestations, Genetics, and Treatment

CPEB1 induces autophagy and promotes apoptosis in ovarian granulosa cells of polycystic ovary syndrome

Acupuncture Improves Endometrial Angiogenesis by Activating PI3K/AKT Pathway in a Rat Model with PCOS

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