通过AKT通路,N6-甲基氨酸脱甲酶FTO与PCOS中的过高雄性质有关
Yuan-Xue Jing1,2,3, Hong-Xing Li1,2,3, Feng Yue1,3
1The First Hospital of Lanzhou University, Lanzhou, China.
概括
脂肪质量和与肥胖相关的蛋白质 (FTO) 在多囊性卵巢综合征 (PCOS) 中被上调,导致过高雄性. 针对FTO可能为PCOS提供新的治疗策略.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 多囊卵巢综合征 (PCOS) 是一种常见的内分泌疾病,其特征是高雄性和排卵问题.
- 脂肪质量和与肥胖相关的蛋白质 (FTO),一种m6A脱甲基酶,与卵巢疾病有关,但其在PCOS病变发生过程中的作用尚不清楚.
研究的目的:
- 研究FTO在PCOS中的机制,重点关注其与高雄性质的关系.
- 探索针对FTO作为PCOS治疗策略的潜力.
主要方法:
- 在临床PCOS样本,PCOS大鼠模型和暴露于二氨酸 (DHT) 的粒状细胞 (GCs) 中分析了FTO水平.
- 评估的m6ARNA甲基化,雄激素水平,类固醇激素合成酶表达和雄激素受体 (AR) /前列腺特异性抗原 (PSA) 水平.
- 利用FTO抑制 (siRNA,麦克洛芬胺酸) 和AKT酸化抑制 (LY294002) 来评估对GCs的影响.
主要成果:
- 在PCOS患者中,FTO表达升高,与m6A水平负相关,但与雄激素水平正相关.
- 在体外,DHT促进了FTO表达,并降低了m6A水平.
- FTO抑制降低了雄激素合成和AR/PSA水平,而FTO抑制则协同降低了GC存活率和增加了细胞循环停止.
结论:
- 在PCOS中,FTO是上调调节的,通过影响雄激素合成和AR信号传递,有助于过高雄激素主义.
- 在GC中,FTO和AR相互作用.
- 准FTO是一个潜在的治疗途径,用于管理PCOS中高雄性质症.
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