Coutinho Eulalia A, Kauffman Alexander S
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Med Sci (Basel). 2019 Aug 2;7(8):84. doi: 10.3390/medsci7080084.
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder, affecting at least 10% of women of reproductive age. PCOS is typically characterized by the presence of at least two of the three cardinal features of hyperandrogenemia (high circulating androgen levels), oligo- or anovulation, and cystic ovaries. Hyperandrogenemia increases the severity of the condition and is driven by increased luteinizing hormone (LH) pulse secretion from the pituitary. Indeed, PCOS women display both elevated mean LH levels, as well as an elevated frequency of LH pulsatile secretion. The abnormally high LH pulse frequency, reflective of a hyperactive gonadotropin-releasing hormone (GnRH) neural circuit, suggests a neuroendocrine basis to either the etiology or phenotype of PCOS. Several studies in preclinical animal models of PCOS have demonstrated alterations in GnRH neurons and their upstream afferent neuronal circuits. Some rodent PCOS models have demonstrated an increase in GnRH neuron activity that correlates with an increase in stimulatory GABAergic innervation and postsynaptic currents onto GnRH neurons. Additional studies have identified robust increases in hypothalamic levels of kisspeptin, another potent stimulator of GnRH neurons. This review outlines the different brain and neuroendocrine changes in the reproductive axis observed in PCOS animal models, discusses how they might contribute to either the etiology or adult phenotype of PCOS, and considers parallel findings in PCOS women.
多囊卵巢综合征（PCOS）是一种常见的生殖内分泌疾病，影响至少10%的育龄女性。PCOS的典型特征是具有高雄激素血症（循环雄激素水平升高）、少排卵或无排卵以及卵巢多囊这三个主要特征中的至少两个。高雄激素血症会加重病情，其由垂体促黄体生成素（LH）脉冲分泌增加所驱动。实际上，PCOS女性不仅平均LH水平升高，而且LH脉冲分泌频率也升高。异常高的LH脉冲频率反映了促性腺激素释放激素（GnRH）神经回路的过度活跃，提示PCOS的病因或表型存在神经内分泌基础。在PCOS临床前动物模型中的多项研究已证明GnRH神经元及其上游传入神经回路存在改变。一些啮齿动物PCOS模型已证明GnRH神经元活动增加，这与GnRH神经元上刺激性GABA能神经支配和突触后电流增加相关。其他研究已确定，另一种GnRH神经元的强效刺激物—— kisspeptin在下丘脑的水平显著升高。本综述概述了在PCOS动物模型中观察到的生殖轴不同的脑和神经内分泌变化，讨论了它们如何可能导致PCOS的病因或成年表型，并考虑了PCOS女性中的平行发现。
