Growth hormone activates PI3K/Akt signaling and inhibits ROS accumulation and apoptosis in granulosa cells of patients with polycystic ovary syndrome.
Growth hormone activates PI3K/Akt signaling and inhibits ROS accumulation and apoptosis in granulosa cells of patients with polycystic ovary syndrome.
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DOI：
10.1186/s12958-020-00677-x
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发表时间：
2020-12-07
期刊：
影响因子：
--
通讯作者：
Huang W
中科院分区：
文献类型：
--
作者：
Gong Y;Luo S;Fan P;Zhu H;Li Y;Huang W
据报道，生长激素（GH）可以通过激活PI3K/Akt信号通路，缓解氧化应激（OS）诱导的某些类型细胞的凋亡。本研究探讨生长激素在多囊卵巢综合征（PCOS）患者OS和颗粒细胞（GCs）凋亡中的作用及其机制。在取卵过程中，从有PCOS和没有PCOS的患者（对照组，n = 32）中收集原发GCs。PCOS患者随机分为接受生长激素治疗（PCOS-GH, n = 30）和不接受生长激素治疗（PCOS- c, n = 31）两组。采用分光光度法和荧光显微镜检测活性氧（ROS）水平。流式细胞术分别采用Annexin V-FITC/PI双染色和JC-1染色检测GC细胞凋亡和线粒体膜电位（MMP）。采用定量逆转录聚合酶链反应和western blotting检测凋亡相关基因和参与PI3K/Akt信号通路蛋白的表达，采用酶联免疫吸附法检测GCs活性caspase-9和caspase-3水平。我们的研究发现，与PCOS-C组相比，PCOS-GH组的GCs中ROS水平和凋亡率显著降低，MMP显著升高（P < 0.05）。PCOS-GH组GCs中FOXO1、Bax、caspase-9、caspase-3 mRNA表达水平显著低于PCOS-C组，Bcl-2 mRNA表达水平显著高于PCOS-C组（P < 0.05）。与PCOS-C组相比，PCOS-GH组GCs中fox01、Bax、cleaved caspase-9/caspase-9和cleaved caspase-3/caspase-3蛋白水平降低，P -PI3K/PI3K、P -Akt/Akt、P - fox01和Bcl-2蛋白水平升高（P < 0.05）。OS诱导PCOS患者细胞凋亡，下调PI3K/Akt信号通路。GH可减轻细胞凋亡，激活PI3K/Akt信号通路。中国临床试验注册。ChiCTR1800019437。预期于2018年10月20日注册。
It is reported that growth hormone (GH) can alleviate oxidative stress (OS) induced apoptosis in some types of cells by activating the PI3K/Akt signaling pathway. This study investigated the role and underlying mechanism of GH in OS and apoptosis in granulosa cells (GCs) of patients with polycystic ovary syndrome (PCOS). Primary GCs were collected from patients with and without PCOS (controls, n = 32) during oocyte retrieval. The patients with PCOS were randomly assigned to take GH treatment (PCOS-GH, n = 30) or without GH treatment (PCOS-C, n = 31). Reactive oxygen species (ROS) level was determined by spectrophotometry and fluorescence microscopy. GC apoptosis and mitochondrial membrane potential (MMP) were detected by Annexin V-FITC/PI double-staining and JC-1 staining, respectively (flow cytometry). The expression of apoptosis-related genes and proteins involved in PI3K/Akt signaling was determined by quantitative reverse-transcription polymerase chain reaction and western blotting, while active caspase-9 and caspase-3 levels of GCs were determined by enzyme-linked immunosorbent assay. Our study found that in GCs of the PCOS-GH group, the ROS levels and apoptotic rates were significantly decreased, whereas MMP was significantly increased when compared to those in the PCOS-C group (P < 0.05). The mRNA levels of FOXO1, Bax, caspase-9, and caspase-3 were significantly decreased, whereas Bcl-2 was increased in GCs of the PCOS-GH group than those in the PCOS-C group (P < 0.05). The protein levels of FOXO1, Bax, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3 were decreased, whereas p-PI3K/PI3K, p-Akt/Akt, p-FOXO1 and Bcl-2 were increased in GCs of the PCOS-GH group, compared with those in the PCOS-C group (P < 0.05). OS induced apoptosis and downregulated the PI3K/Akt signaling pathway in patients with PCOS. GH could alleviate apoptosis and activate the PI3K/Akt signaling pathway. Chinese Clinical Trial Registry. ChiCTR1800019437. Prospectively registered on October 20, 2018.
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