Altered aquaporin expression in women with polycystic ovary syndrome: hyperandrogenism in follicular fluid inhibits aquaporin-9 in granulosa cells through the phosphatidylinositol 3-kinase pathway
Altered aquaporin expression in women with polycystic ovary syndrome: hyperandrogenism in follicular fluid inhibits aquaporin-9 in granulosa cells through the phosphatidylinositol 3-kinase pathway
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DOI：
10.1093/humrep/deq078
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发表时间：
2010-06-01
影响因子：
6.1
通讯作者：
Huang, He-Feng
中科院分区：
文献类型：
--
作者：
Qu, Fan;Wang, Fang-Fang;Huang, He-Feng
背景资料：本研究旨在探讨多囊卵巢综合征（PCOS）患者卵泡液（FF）中高雄激素血症与颗粒细胞（GC）水通道蛋白9（AQP-9）表达的关系。检测FF患者血清总睾酮（TT）、游离雄激素指数（FAI）、性激素结合球蛋白（SHBG）、FSH、LH和雌二醇。结果：AQP-9蛋白定位于人胃癌细胞的胞核、胞浆和胞膜，胞浆内有AQP-9蛋白的表达，胞浆内有AQP-9蛋白的表达，胞浆内有AQP-9蛋白的表达，胞浆内有AQP-9蛋白的表达。与对照组相比，PCOS妇女FF中TT、FAI和LH水平均较高，SHBG水平较低（P分别为0.0145、0.0001、0.0191、0.0001）。PCOS患者GCs中AQP-9 mRNA水平与FF中TT、SHBG水平和FAI密切相关（P分别为0.0020、0.0001、0.0020）。在体外实验中，DHT（10（-9）mol/l）降低对照GC中AQP-9 mRNA（12 h最低）和蛋白水平（P分别为0.0005、0.0247）。磷脂酰肌醇3-激酶（PI 3 K）抑制剂LY 294002可减弱DHT对AQP-9 mRNA表达的抑制作用（P = 0.0013）。50 μ mol的4-羟基汞苯甲酸钠（PMB）和10（-9）mol/l的二氢睾酮（DHT）分别抑制低渗液中GCs的肿胀（P = 0.0350，0.0027）。
Background: The present study was designed to evaluate whether the alteration of aquaporin-9 (AQP-9) expression in granulosa cells (GCs) of patients with polycystic ovary syndrome (PCOS) was associated with the hyperandrogenism in follicular fluid (FF).Methods: We recruited infertile women with PCOS (n = 14) and infertile women with tubal blockage (controls, n = 31) for this study. We examined total testosterone (TT), free androgen index (FAI), sex hormone-binding globulin (SHBG), FSH, LH and estradiol in FF. Real-time PCR and western blotting were performed to assess AQP-9 expression in GCs, including effects of dihydrotestosterone (DHT) in vitro.Results: AQP-9 protein was localized in the nucleus, cytoplasm and cell membrane of the human GCs. The TT, FAI and LH levels were all higher, and SHBG levels lower, in the FF of women with PCOS versus controls (P = 0.0145, 0.0001, 0.0191, 0.0001, respectively). AQP-9 mRNA level in GCs of patients with PCOS was tightly correlated with the TT, SHBG levels and FAI in FF (P = 0.0020, 0.0001, 0.0020, respectively). In vitro, DHT (10(-9) mol/l) decreased AQP-9 mRNA (lowest at 12 h) and protein levels in control GCs (P = 0.0005, 0.0247, respectively). The inhibitory effect of DHT on AQP-9 mRNA was attenuated by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor (P = 0.0013). Fifty micromolar 4-(hydroxymercuri) benzoic acid sodium salt (PMB) and 10(-9) mol/l DHT blunted the swelling of GCs in hypotonic medium, respectively (P = 0.0350, 0.0027).Conclusion: Hyperandrogenism in FF of women with PCOS inhibited AQP-9 in GCs through the PI3K pathway.