Blank S K, McCartney C R, Marshall J C
The Center for Research in Reproduction, Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA.
Hum Reprod Update. 2006 Jul-Aug;12(4):351-61. doi: 10.1093/humupd/dml017. Epub 2006 May 2.
Polycystic ovary syndrome (PCOS) is a common clinical disorder characterized by ovulatory dysfunction and hyperandrogenaemia. A neuroendocrine hallmark of PCOS is persistently rapid LH (GnRH) pulsatility, which favours pituitary synthesis of LH over that of FSH and contributes to the increased LH concentrations and LH : FSH ratios typical of PCOS. Inadequate FSH levels contribute to impaired follicular development, whereas elevated LH levels augment ovarian androgen production. Whereas luteal phase elevations in progesterone normally slow GnRH pulse frequency, women with PCOS do not experience normal progesterone-mediated slowing, due in part to impaired hypothalamic progesterone sensitivity. This reduction in hypothalamic progesterone sensitivity appears to be mediated by elevated androgens because sensitivity can be restored with the androgen receptor blocker flutamide. The ovulatory and hormonal abnormalities associated with PCOS generally present during puberty, typically associated with hyperandrogenaemia. Along with elevated LH concentration and pulsatility, some girls with hyperandrogenaemia have impaired hypothalamic progesterone sensitivity similar to that seen in adult women with PCOS. We propose that peripubertal hyperandrogenaemia may lead to persistently rapid GnRH pulse frequency via impaired hypothalamic feedback inhibition. The subsequent abnormalities in gonadotropin secretion, androgen production and ovulatory function may support progression towards the adult PCOS phenotype.
多囊卵巢综合征（PCOS）是一种常见的临床疾病，其特征为排卵功能障碍和高雄激素血症。PCOS的一个神经内分泌特征是LH（GnRH）脉冲频率持续快速，这有利于垂体合成LH而非FSH，并导致PCOS典型的LH浓度升高和LH:FSH比值增加。FSH水平不足导致卵泡发育受损，而LH水平升高则增加卵巢雄激素的产生。正常情况下，黄体期孕酮升高会减缓GnRH脉冲频率，但PCOS女性不会出现正常的孕酮介导的减缓，部分原因是下丘脑对孕酮的敏感性受损。下丘脑孕酮敏感性的降低似乎是由雄激素升高介导的，因为使用雄激素受体阻滞剂氟他胺可以恢复敏感性。与PCOS相关的排卵和激素异常通常在青春期出现，通常与高雄激素血症有关。除了LH浓度和脉冲频率升高外，一些高雄激素血症女孩的下丘脑孕酮敏感性受损，类似于成年PCOS女性。我们认为青春期前后的高雄激素血症可能通过下丘脑反馈抑制受损导致GnRH脉冲频率持续快速。随后促性腺激素分泌、雄激素产生和排卵功能的异常可能支持向成年PCOS表型的进展。
