Climacteric Section, Department of Obstetrics and Gynecology, Universidade Federal de São Paulo Escola Paulista de Medicina (UNIFESP/EPM), 66 Embaú Street, Vila Clementino, 04039-060 São Paulo, SP, Brazil.
Laboratory of Molecular and Structural Gynecology, Department of Obstetrics and Gynecology, University of São Paulo School of Medicine, 455 Dr. Arnaldo Avenue, Room 4121, Cerqueira Cesar, 01246-903 São Paulo, SP, Brazil.
Biomed Res Int. 2017;2017:9058307. doi: 10.1155/2017/9058307. Epub 2017 Dec 21.
We aim to assess the effects of metformin treatment on metabolic and endocrine parameters and genes expression related to the insulin-responsive pathway in polycystic ovary syndrome (PCOS). This study comprises twenty-eight obese mice divided into three metformin-treated groups for seven and twenty days and eight nonobese and nontreated ones. We found a significant decrease in glycemia after metformin treatment at days seven and twenty. However, we did not observe differences in body weight measurement. Histologically, after twenty days we observed follicular development with regression of androgenic effects. Levels of IGF-1R protein expression were low after twenty days of treatment, but LEP proteins showed an overexpression in the ovarian stroma. We assessed the IGF-1R and LEP mRNAs levels; data showed a significant overexpression of LEP after seven days of treatment, while the IGF-1R was downregulated. Metformin therapy seems to exert a beneficial effect on histological and anovulatory features, reducing follicular number and pyknosis formation, possibly involved in the reversion of androgenic stimulus. Expression of IGF-1 and LEPR indicates a relevant role in androgenic features reversion present in PCOS, hormonal equilibrium, body weight regulation, and glucose metabolism, therefore, under phenotype obesity and infertility regulation in this model.
我们旨在评估二甲双胍治疗对多囊卵巢综合征（PCOS）胰岛素反应途径的代谢和内分泌参数及基因表达的影响。这项研究包括 28 只肥胖小鼠，分为 3 组，每组接受 7 天和 20 天的二甲双胍治疗，以及 8 只非肥胖未治疗的对照。我们发现，在第 7 天和第 20 天的二甲双胍治疗后，血糖显著降低。然而，我们并没有观察到体重测量的差异。组织学观察发现，经过 20 天的治疗后，卵泡发育并伴有雄激素作用的消退。IGF-1R 蛋白表达水平在治疗 20 天后降低，但 LEP 蛋白在卵巢基质中过度表达。我们评估了 IGF-1R 和 LEP mRNAs 水平；数据显示，治疗 7 天后 LEP 显著过表达，而 IGF-1R 则下调。二甲双胍治疗似乎对组织学和无排卵特征具有有益的影响，减少卵泡数量和核固缩形成，可能参与雄激素刺激的逆转。IGF-1 和 LEPR 的表达表明，在 PCOS 中存在与雄激素特征逆转、激素平衡、体重调节和葡萄糖代谢相关的重要作用，因此在该模型中调节表型肥胖和不孕。
