Dehydroepiandrosterone stimulates inflammation and impairs ovarian functions of polycystic ovary syndrome
Dehydroepiandrosterone stimulates inflammation and impairs ovarian functions of polycystic ovary syndrome
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脱氢表雄酮刺激炎症并损害多囊卵巢综合征的卵巢功能
DOI：
10.1002/jcp.27501
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发表时间：
2019-05-01
影响因子：
5.6
通讯作者：
Yan, Qiu
中科院分区：
文献类型：
--
作者：
Li, Yulin;Zheng, Qin;Yan, Qiu
多囊卵巢综合征（PCOS）是育龄妇女不孕的最常见原因之一。其特征是排卵功能障碍、多囊卵巢和高雄激素血症。炎症可能是PCOS发病机制的关键因素。然而，炎症细胞因子与PCOS发生发展之间的关系尚未见报道。为探讨炎症因子与多囊卵巢综合征（PCOS）的关系，采用蛋白质芯片技术检测脱氢表雄酮（DHEA）诱导PCOS大鼠血清蛋白质的变化，并采用酶联免疫吸附试验（ELISA）检测IFN-γ的浓度。与对照组大鼠相比，DHEA诱导的多囊卵巢综合征大鼠的干扰素-γ水平下降，而氟他胺（雄激素受体拮抗剂）治疗的大鼠部分恢复了这一水平。PCOS患者血清IFN-γ水平也低于健康妇女。使用卵巢颗粒细胞（KGN），我们证明，DHEA下调IFN-γ的表达和分泌的剂量和时间依赖性的方式，这可以在一定程度上恢复与氟替卡松治疗。氟替卡松可改善DHEA对细胞增殖的抑制作用和促进细胞凋亡的作用。IFN-γ促进KGN细胞增殖，但抑制其凋亡，DHEA通过激活下游PI 3 K/AKT信号通路抑制KGN细胞凋亡。上述结果表明DHEA通过下调IFN-γ的表达抑制卵巢颗粒细胞增殖并促进其凋亡，而IFN-γ的表达可被氟替卡松恢复，IFN-γ可能作为PCOS检测的潜在炎症标志物。
Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in child-bearing-age women. It is characterized by ovulation dysfunction, polycystic ovaries, and hyperandrogenism. Inflammation is likely to be a crucial contributor to the pathogenesis of PCOS. However, the association between the inflammatory cytokines and the development of PCOS has not been reported. To explore the relationship between the inflammatory cytokines and PCOS, alterations of serum proteins in dehydroepiandrosterone (DHEA)-induced PCOS rats were screened by protein array, and the concentration of IFN-gamma was further measured by using enzyme-linked immunosorbent assay (ELISA). DHEA-induced PCOS rats had a decreased level of IFN-gamma compared with the control rats, which was restored partly in flutamide (an androgen receptor antagonist)-treated rats. Moreover, the level of IFN-gamma in serum of patients with PCOS was also lower than that in healthy women. Using the ovarian granulosa cells (KGN), we demonstrated that DHEA downregulated the expression and secretion of IFN-gamma in dose- and time-dependent manners, which could be restored to some extent by treating with flutamide. Furthermore, flutamide ameliorated the inhibitory effect on cell proliferation and promotive effect on cell apoptosis by DHEA. The results also revealed that IFN-gamma promoted the proliferation but inhibited the apoptosis of KGN cells, which was suppressed by DHEA via activating the downstream PI3K/AKT signaling pathway. Taken together, these results showed that DHEA inhibited the proliferation and promoted the apoptosis of ovarian granulosa cells through downregulating the expression of IFN-gamma which could be restored by flutamide, and IFN-gamma may serve as a potential inflammatory biomarker for PCOS detection.