Regulation of Androgen Receptor Expression Alters AMPK Phosphorylation in the Endometrium: In Vivo and In Vitro Studies in Women with Polycystic Ovary Syndrome.
Regulation of Androgen Receptor Expression Alters AMPK Phosphorylation in the Endometrium: In Vivo and In Vitro Studies in Women with Polycystic Ovary Syndrome.
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DOI：
10.7150/ijbs.13109
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发表时间：
2015
影响因子：
9.2
通讯作者：
Shao R
中科院分区：
文献类型：
--
作者：
Li X;Pishdari B;Cui P;Hu M;Yang HP;Guo YR;Jiang HY;Feng Y;Billig H;Shao R
多囊卵巢综合征（PCOS）患者生殖失败的部分原因可能是子宫内膜功能障碍。然而，没有研究调查生理和病理条件下子宫内膜中雄激素、雄激素受体（AR）表达和腺苷酸活化蛋白激酶（AMPK）活化之间的因果关系。在本研究中，我们发现：1）非PCOS和PCOS患者子宫内膜AR表达水平在月经周期中波动; 2）非PCOS患者子宫内膜p-AMPKα表达呈月经周期依赖性变化，而PCOS患者则无此变化; 3）PCOS患者增生期AR表达高于非PCOS患者，而AMPKα激活（4）在子宫内膜增生症中，AR和Ki-67共定位于上皮细胞核。重要的是，我们使用体外人体组织培养和体内5α-二氢睾酮处理的大鼠模型，表明雄激素对AMPKα激活的作用可能是通过核AR介导的，特别是在上皮细胞中。总的来说，我们提供的证据表明，AR表达和AMPKα激活依赖于月经周期的阶段和PCOS的存在，数据表明，AR介导的AMPKα激活的调节可能在子宫内膜增生的发展中发挥作用。
The failure of reproductive success in polycystic ovary syndrome (PCOS) patients could be in part due to endometrial dysfunction. However, no studies have investigated any causality between androgen, androgen receptor (AR) expression, and adenosine monophosphate activated protein kinase (AMPK) activation in the endometrium under physiological and pathological conditions. In the present study, we show that 1) endometrial AR expression levels fluctuate in non-PCOS and PCOS patients during the menstrual cycle; 2) the menstrual phase-dependent alteration of p-AMPKα expression occurs in non-PCOS patients but not in PCOS patients; 3) AR expression is higher in PCOS patients than non-PCOS patients during hyperplasia while AMPKα activation (indicated by the ratio of p-AMPKα to AMPKα); and 4) co-localization of AR and Ki-67 in epithelial cell nuclei is observed in endometrial hyperplasia. Importantly, using in vitro human tissue culture and an in vivo 5α-dihydrotestosterone-treated rat model, we show that the action of androgen on AMPKα activation is likely mediated through nuclear AR, especially in epithelial cells. Collectively, we present evidence that AR expression and AMPKα activation depend on menstrual cycle phase and the presence of PCOS, and the data suggest that AR-mediated regulation of AMPKα activation might play a role in the development of endometrial hyperplasia.