GDF-15 levels in patients with polycystic ovary syndrome treated with metformin: a combined clinical and in silico pathway analysis.

IF 1.6 4区医学 Q4 ENDOCRINOLOGY & METABOLISM

Archives of Endocrinology Metabolism Pub Date : 2024-08-27 eCollection Date: 2024-01-01 DOI:10.20945/2359-4292-2023-0416

Fernanda M V Magalhães, Rodrigo M C Pestana, Cláudia N Ferreira, Ieda F O Silva, Ana L Candido, Flávia R Oliveira, Fernando M Reis, Karina B Gomes

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引用次数: 0

Abstract

Objective: Polycystic ovary syndrome (PCOS) is an endocrine disease characterized by metabolic, reproductive, and psychological manifestations. Growth and differentiation factor 15 (GDF-15) is a cytokine associated with metabolic and inflammatory disorders. Metformin is commonly used for the treatment of PCOS. We investigated the relationship between GDF-15 levels and PCOS, the effect of metformin on GDF-15 levels, and potential biologic pathways related to GDF-15.

Subjects and methods: The study included 35 women with PCOS and 32 women without PCOS (controls). Both groups were compared in terms of GDF-15 levels. Additional analysis was conducted on samples from 22 women with PCOS who were treated with either metformin (n = 7) or placebo (n = 15), retrieved from a previous randomized, controlled trial. Levels of GDF-15 were measured using MILLIPLEX. The biologic pathways related to GDF-15 were evaluated using the databases STRING, SIGNOR, and Pathway Commons. The statistical analysis was conducted using the software SPSS.

Results: Levels of GDF-15 were higher in the PCOS group compared with the non-PCOS group (p = 0.039). Among women with PCOS, GDF-15 levels were higher in those treated with metformin compared with placebo (p = 0.007). The proteins related to GDF-15 overlapped between the databases, and a significant interaction was found between GDF-15 and proteins related to PCOS and its complications, including those related to estrogen response, oxidative stress, ovarian infertility, interleukin (IL)-18, IL-4, the ratio of advanced glycation end products to their receptor (AGE/RAGE), leptin, transforming growth factor beta (TGF-β), adipogenesis, and insulin.

Conclusion: The findings of the present study suggest a relationship between GDF-15 and PCOS and a potential increase in GDF-15 levels with metformin treatment. An additional finding was that GDF-15 could be involved in biologic pathways related to PCOS complications.

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接受二甲双胍治疗的多囊卵巢综合征患者体内的 GDF-15 水平：临床与硅路径联合分析。

目的：多囊卵巢综合征（PCOS）是一种以代谢、生殖和心理表现为特征的内分泌疾病。生长与分化因子 15（GDF-15）是一种与代谢和炎症紊乱有关的细胞因子。二甲双胍是治疗多囊卵巢综合征的常用药物。我们研究了 GDF-15 水平与多囊卵巢综合征之间的关系、二甲双胍对 GDF-15 水平的影响以及与 GDF-15 相关的潜在生物途径：研究包括35名患有多囊卵巢综合征的女性和32名未患有多囊卵巢综合征的女性（对照组）。对两组的 GDF-15 水平进行了比较。此外，还对 22 名患有多囊卵巢综合症的妇女的样本进行了分析，这些妇女接受了二甲双胍（7 人）或安慰剂（15 人）的治疗，这些样本是从之前的随机对照试验中提取的。使用 MILLIPLEX 检测了 GDF-15 的水平。使用 STRING、SIGNOR 和 Pathway Commons 数据库评估了与 GDF-15 相关的生物通路。统计分析使用 SPSS 软件进行：结果：与非多囊卵巢综合征组相比，多囊卵巢综合征组的 GDF-15 水平更高（p = 0.039）。在多囊卵巢综合征妇女中，与安慰剂相比，二甲双胍治疗组的 GDF-15 水平更高（p = 0.007）。与GDF-15相关的蛋白质在数据库中有所重叠，并且发现GDF-15与PCOS及其并发症相关的蛋白质之间存在显著的相互作用，包括与雌激素反应、氧化应激、卵巢不孕、白细胞介素（IL）-18、IL-4、高级糖化终产物与其受体（AGE/RAGE）的比率、瘦素、转化生长因子β（TGF-β）、脂肪生成和胰岛素相关的蛋白质：结论：本研究结果表明，GDF-15与多囊卵巢综合征之间存在关系，二甲双胍治疗可能会增加GDF-15的水平。结论：本研究结果表明，GDF-15与多囊卵巢综合征有关系，二甲双胍治疗可能会增加GDF-15的水平。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Archives of Endocrinology Metabolism Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

2.90

自引率

5.90%

发文量

107

审稿时长

7 weeks

期刊介绍： The Archives of Endocrinology and Metabolism - AE&M – is the official journal of the Brazilian Society of Endocrinology and Metabolism - SBEM, which is affiliated with the Brazilian Medical Association. Edited since 1951, the AE&M aims at publishing articles on scientific themes in the basic translational and clinical area of Endocrinology and Metabolism. The printed version AE&M is published in 6 issues/year. The full electronic issue is open access in the SciELO - Scientific Electronic Library Online e at the AE&M site: www.aem-sbem.com. From volume 59 on, the name was changed to Archives of Endocrinology and Metabolism, and it became mandatory for manuscripts to be submitted in English for the online issue. However, for the printed issue it is still optional for the articles to be sent in English or Portuguese. The journal is published six times a year, with one issue every two months.