Indiana University School of Medicine, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Indianapolis, IN 46202, USA.
Steroids. 2012 Mar 10;77(4):300-5. doi: 10.1016/j.steroids.2011.12.003. Epub 2011 Dec 8.
Chronic low-grade inflammation has emerged as a key contributor to the pathogenesis of Polycystic Ovary Syndrome (PCOS). A dietary trigger such as glucose is capable of inciting oxidative stress and an inflammatory response from mononuclear cells (MNC) of women with PCOS, and this phenomenon is independent of obesity. This is important because MNC-derived macrophages are the primary source of cytokine production in excess adipose tissue, and also promote adipocyte cytokine production in a paracrine fashion. The proinflammatory cytokine tumor necrosis factor-α (TNFα) is a known mediator of insulin resistance. Glucose-stimulated TNFα release from MNC along with molecular markers of inflammation are associated with insulin resistance in PCOS. Hyperandrogenism is capable of activating MNC in the fasting state, thereby increasing MNC sensitivity to glucose; and this may be a potential mechanism for promoting diet-induced inflammation in PCOS. Increased abdominal adiposity is prevalent across all weight classes in PCOS, and this inflamed adipose tissue contributes to the inflammatory load in the disorder. Nevertheless, glucose ingestion incites oxidative stress in normal weight women with PCOS even in the absence of increased abdominal adiposity. In PCOS, markers of oxidative stress and inflammation are highly correlated with circulating androgens. Chronic suppression of ovarian androgen production does not ameliorate inflammation in normal weight women with the disorder. Furthermore, in vitro studies have demonstrated the ability of pro-inflammatory stimuli to upregulate the ovarian theca cell steroidogenic enzyme responsible for androgen production. These findings support the contention that inflammation directly stimulates the polycystic ovary to produce androgens.
慢性低度炎症已成为多囊卵巢综合征（PCOS）发病机制的关键因素。葡萄糖等饮食诱因能够引发 PCOS 女性单核细胞（MNC）的氧化应激和炎症反应，而这种现象与肥胖无关。这很重要，因为 MNC 衍生的巨噬细胞是过量脂肪组织中细胞因子产生的主要来源，并且还以旁分泌方式促进脂肪细胞细胞因子的产生。促炎细胞因子肿瘤坏死因子-α（TNFα）是胰岛素抵抗的已知介质。MNC 对葡萄糖刺激的 TNFα释放以及炎症的分子标志物与 PCOS 中的胰岛素抵抗有关。在禁食状态下，高雄激素血症能够激活 MNC，从而增加 MNC 对葡萄糖的敏感性；这可能是促进 PCOS 中饮食诱导炎症的潜在机制。在 PCOS 中，所有体重类别都普遍存在腹部肥胖，这种发炎的脂肪组织导致该疾病的炎症负荷增加。尽管如此，即使没有腹部肥胖增加，葡萄糖摄入也会在患有 PCOS 的正常体重女性中引发氧化应激。在 PCOS 中，氧化应激和炎症的标志物与循环雄激素高度相关。慢性抑制卵巢雄激素产生并不能改善患有该疾病的正常体重女性的炎症。此外，体外研究表明，促炎刺激物能够上调负责雄激素产生的卵巢泡膜细胞类固醇生成酶。这些发现支持炎症直接刺激多囊卵巢产生雄激素的观点。
