The central role for androgens in development of polycystic ovary syndrome

多囊卵巢综合征（PCOS）是女性中最常见的激素紊乱，影响5-10%的育龄妇女。它是不孕不育的主要原因，但它也与晚年患2型糖尿病（晚发性或非胰岛素依赖型糖尿病）和心脏病的风险增加3至4倍有关。此外，由于人口中肥胖的发病率急剧增加，越来越多的PCOS年轻女性患有糖尿病。有证据表明，患有多囊卵巢综合征的女性能量平衡不正常，这可能使她们更容易体重增加。我们对多囊卵巢综合征的病因知之甚少，这限制了我们目前的治疗选择，或预防这种疾病的长期后果。然而，我们确实知道，血液中雄激素（雄性激素，如睾酮）水平高于正常水平是多囊卵巢综合征中最常见的激素异常，动物模型的证据表明，在胎儿时期暴露于过量的睾丸激素会导致我们在多囊卵巢综合征女性中认识到的许多特征。但是，关于卵巢（和肾上腺）产生雄激素，以及雄激素如何影响生育能力和导致糖尿病和心脏病的代谢紊乱，还有很多需要了解的。在拟议的工作计划中，我们将使用动物模型和人体研究（来自卵巢或脂肪组织的细胞）来探索雄激素在多囊卵巢综合征起源中的作用。特别是，我们想知道暴露于过量的雄激素是否对卵巢的功能（从胎儿到成年）和能量平衡有直接影响，以及脂肪组织中控制这一点的信号。我们还想研究（在老鼠身上）阻断雄性激素在幼龄动物身上的作用是否能预防（或至少减少）成年期常见的生殖和代谢异常。这将给我们一个更好的机会，找到有效的方法来改善排卵（和生育）的机会，预防和治疗2型糖尿病。

Polycystic ovary syndrome (PCOS) is the commonest hormone disorder in women, affecting between 5-10% of women of reproductive age. It is a major cause of infertility but it is also associated with a 3 to 4-fold increase in the risk of developing type 2 diabetes (late onset, or non insulin-dependent diabetes), and heart disease, in later life. Furthermore, because of the steeply increasing incidence of obesity in the population, more and more young women with PCOS are getting diabetes. There is evidence that women with PCOS have abnormal energy balance and that may make them more susceptible to weight gain. We know very little about the cause or causes of PCOS, which currently limits our options for treatment, or prevention of the long-term consequences of the disorder. We do however know that higher than normal blood levels of androgens (male hormones such as testosterone) are the most common hormone abnormality in PCOS and there is evidence from animal models that exposure to excess testosterone during fetal life leads many of the features that we recognise in women with PCOS. But there is still much to be learned about both the production of androgens by the ovary (and adrenal gland) and how androgens affect both fertility and metabolic disorders leading to diabetes and heart disease. In the proposed programme of work, we shall use both animal models and human studies (of cells from the ovary or fat tissue) to explore the role of androgens in the origin of PCOS. In particular, we want to know whether exposure to excess androgen has a direct effect on the way the ovary functions (from fetal life to adulthood) and on energy balance - and the signals in fat tissue that control this. We also want to study (in mice) whether blocking the effects of androgen in young animals can prevent (or at least reduce) the reproductive and metabolic abnormalities that are common in adulthood. This will give us a much better chance of finding effective ways of in improving the chances of ovulation (and fertility) and in preventing and treating type 2 diabetes.