Dunaif A
Pennsylvania State University College of Medicine, Hershey 17033, USA.
Endocr Rev. 1997 Dec;18(6):774-800. doi: 10.1210/edrv.18.6.0318.
It is now clear that PCOS is often associated with profound insulin resistance as well as with defects in insulin secretion. These abnormalities, together with obesity, explain the substantially increased prevalence of glucose intolerance in PCOS. Moreover, since PCOS is an extremely common disorder, PCOS-related insulin resistance is an important cause of NIDDM in women (Table 3). The insulin resistance in at least 50% of PCOS women appears to be related to excessive serine phosphorylation of the insulin receptor. A factor extrinsic to the insulin receptor, presumably a serine/threonine kinase, causes this abnormality and is an example of an important new mechanism for human insulin resistance related to factors controlling insulin receptor signaling. Serine phosphorylation appears to modulate the activity of the key regulatory enzyme of androgen biosynthesis, P450c17. It is thus possible that a single defect produces both the insulin resistance and the hyperandrogenism in some PCOS women (Fig. 19). Recent studies strongly suggest that insulin is acting through its own receptor (rather than the IGF-I receptor) in PCOS to augment not only ovarian and adrenal steroidogenesis but also pituitary LH release. Indeed, the defect in insulin action appears to be selective, affecting glucose metabolism but not cell growth. Since PCOS usually has a menarchal age of onset, this makes it a particularly appropriate disorder in which to examine the ontogeny of defects in carbohydrate metabolism and for ascertaining large three-generation kindreds for positional cloning studies to identify NIDDM genes. Although the presence of lipid abnormalities, dysfibrinolysis, and insulin resistance would be predicted to place PCOS women at high risk for cardiovascular disease, appropriate prospective studies are necessary to directly assess this.
现在已经明确，多囊卵巢综合征（PCOS）常与严重的胰岛素抵抗以及胰岛素分泌缺陷相关。这些异常情况，再加上肥胖，解释了PCOS中糖耐量异常患病率大幅增加的原因。此外，由于PCOS是一种极为常见的疾病，PCOS相关的胰岛素抵抗是女性非胰岛素依赖型糖尿病（NIDDM）的一个重要原因（表3）。至少50%的PCOS女性的胰岛素抵抗似乎与胰岛素受体的丝氨酸磷酸化过度有关。胰岛素受体外部的一个因素，大概是一种丝氨酸/苏氨酸激酶，导致了这种异常，这是与控制胰岛素受体信号传导的因素相关的人类胰岛素抵抗的一个重要新机制的例子。丝氨酸磷酸化似乎调节雄激素生物合成的关键调节酶P450c17的活性。因此，在一些PCOS女性中，单一缺陷可能同时导致胰岛素抵抗和高雄激素血症（图19）。最近的研究强烈表明，在PCOS中胰岛素通过其自身受体（而非胰岛素样生长因子-I受体）发挥作用，不仅增强卵巢和肾上腺的类固醇生成，还增强垂体促黄体生成素（LH）的释放。事实上，胰岛素作用的缺陷似乎具有选择性，影响葡萄糖代谢但不影响细胞生长。由于PCOS通常在初潮年龄发病，这使其成为一个特别适合研究碳水化合物代谢缺陷个体发育以及确定用于定位克隆研究以鉴定NIDDM基因的大型三代亲属的疾病。尽管预计脂质异常、纤维蛋白溶解异常和胰岛素抵抗的存在会使PCOS女性患心血管疾病的风险很高，但仍需要进行适当的前瞻性研究来直接评估这一点。
