Assessment of Adipocyte Function in Women with PCOS

多囊卵巢综合征(PCOS)影响多达10%的育龄妇女，其特点是 循环雄激素水平升高、胰岛素抵抗、血脂异常和肥胖。然而， 多囊卵巢综合征代谢综合征发生的分子机制尚不清楚。 多囊卵巢综合征和女性阻塞性睡眠呼吸暂停(OSA)之间的相互作用可能起到关键的作用，但 在这些病理过程中扮演的重要角色。尽管最近OSA与胰岛素抵抗之间存在联系，但 研究发现，患有多囊卵巢综合征的肥胖女性患阻塞性睡眠呼吸暂停综合征的可能性是体重匹配的30倍 对于没有多囊卵巢综合征的女性，大多数关于OSA和新陈代谢的研究都是在男性身上进行的。这个 这一应用的中心假设是OSA是胰岛素形成的一个新的危险因素 多囊卵巢综合征患者脂肪组织中的耐药性。我们将通过测量胰岛素来检验这一假设 肥胖型多囊卵巢综合征合并阻塞性睡眠呼吸暂停患者治疗前后原发脂肪细胞的敏感性 为OSA进行干预。胰岛素信号转导和脂代谢的调节将在 并与体内获得的值进行比较。此外，我们还将确定在 循环糖皮质激素和酶110对脂肪细胞中糖皮质激素的局部激活 HSD1对脂肪细胞胰岛素的作用。最后，调节降低内源性卵巢雄激素的作用 肥胖的患有OSA的PCOS妇女的脂肪细胞中胰岛素信号的产生将被测定，也将被测定 给予患者外源性雌激素或黄体酮的效果。总的来说，这些研究将包括 一个更大的SCOR应用程序的组成部分，该应用程序将对 OSA和循环雄激素在胰岛素抵抗、肥胖和代谢中的作用 多囊卵巢综合征妇女的症状。 相关性：患有多囊卵巢综合征的女性患有肥胖、代谢综合征、性激素失调 合成与阻塞性睡眠呼吸暂停。然而，这些不同疾病之间的相互联系是 不是很清楚。作为综合协作项目的一部分，该应用程序将直接调查 口服空腹血糖和雄激素对PCOS患者脂肪细胞胰岛素敏感性的影响 经过治疗干预后。

Polycystic ovary syndrome (PCOS) affects up to 10% of women of reproductive age, and is characterized by elevation in circulating androgen levels, insulin resistance, dyslipidemia and obesity. However, the molecular mechanisms that underlie the development of the metabolic syndrome in PCOS remain unclear. The interplay between PCOS and obstructive sleep apnea (OSA) in women may play a critical but under appreciated role in these pathologies. Despite the recent linkage between OSA and insulin resistance, and the finding that obese women with PCOS are up to 30 times more likely to develop OSA as weight matched women without PCOS, most of the studies on OSA and metabolism have been conducted in men. The central hypothesis of this application is that OSA is a novel risk factor for the development of insulin resistance in adipose tissue in women with PCOS. We will test this hypothesis by measuring insulin sensitivity in primary adipocytes from obese PCOS women with OSA, before and after therapeutic intervention for the OSA. Insulin signal transduction and regulation of lipid metabolism will be assayed in vitro and compared to values obtained in vivo. Additionally, we will determine the role alterations in circulating glucocorticoids and the localized activation of glucocorticoids in adipocytes by the enzyme 110- HSD1 on adipocytic insulin action. Finally, the effects of modulating reducing endogenous ovarian androgen production on insulin signaling in adipocytes from obese PCOS women with OSA will be determined, as will the effects of giving exogenous estrogen or progesterone to patients. Together, these studies will comprise an integral part of a larger SCOR application that will undertake a comprehensive examination of the role of OSA and circulating androgen on the development on insulin resistance, obesity and the metabolic syndrome in women with PCOS. Relevance: Women with PCOS suffer from obesity, metabolic syndrome, dysregulation of sex steroid synthesis and obstructive sleep apnea. However, the inter connections between these various disorders is not well understood. As part of an integrative collaborative project, this application will directly investigate the effects of OSA and androgens on insulin sensitivity in adipocyte biopsies from PCOS patients before and after therapeutic interventions.