Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity is a major postnatal factor. The variety of pathways involved and lack of a common thread attests to the multifactorial nature and heterogeneity of the syndrome. Further research into the fundamental basis of the disorder will be necessary to optimally correct androgen levels, ovulation, and metabolic homeostasis.

中文翻译：

---

多囊卵巢综合征 (PCOS) 的发病机制：重新审视 PCOS 作为功能性卵巢雄激素过多症的假说。


多囊卵巢综合征（PCOS）被推测是由 1989 年至 1995 年雄激素分泌失调导致的功能性卵巢雄激素过多症（FOH）引起的。随后的研究支持并放大了这一假设。当定义为无法解释的高雄激素性少排卵时，三分之二的 PCOS 病例具有功能上典型的 FOH，其特征是 17-羟基孕酮对促性腺激素刺激的高反应性。其余三分之二的 PCOS 患者在抑制肾上腺雄激素产生后，可通过睾酮升高检测到 FOH。大约 3% 的 PCOS 患有相关的孤立性功能性肾上腺雄激素过多症。其余多囊卵巢综合症病例症状较轻，缺乏类固醇分泌异常的证据；其中大多数人肥胖，我们推测这是导致他们出现非典型多囊卵巢综合症的原因。大约一半患有多囊卵巢形态 (PCOM) 的正常女性存在亚临床 FOH 相关的类固醇生成缺陷。长期培养的经典 PCOS 患者多囊卵巢的卵泡膜细胞具有内在的类固醇生成失调，这可以解释 FOH 典型的类固醇生成异常。这些细胞过度表达大多数类固醇生成酶，特别是细胞色素 P450c17。通过全基因组关联筛选鉴定出的蛋白质在正常卵泡膜细胞中在正常和肿瘤发育 1A.V2 中差异表达，在体外复制了这种 PCOS 表型。大约一半的 PCOS 患者会出现肥胖相关和/或内在胰岛素抵抗的代谢综合征，代偿性高胰岛素血症具有组织选择性效应，包括加重雄激素过多症。多囊卵巢综合症似乎是一种复杂的特征，是多种遗传和环境因素相互作用的结果。 遗传因素包括 PCOM、高雄激素血症、胰岛素抵抗和胰岛素分泌缺陷。环境因素包括产前雄激素暴露和胎儿生长不良，而获得性肥胖是主要的产后因素。涉及的途径多种多样且缺乏共同线索，证明了该综合征的多因素性质和异质性。为了最佳地纠正雄激素水平、排卵和代谢稳态，有必要对该疾病的基本原理进行进一步研究。