Impaired steroid hormone feedback in polycystic ovary syndrome: Evidence from preclinical models for abnormalities within central circuits controlling fertility.
Impaired steroid hormone feedback in polycystic ovary syndrome: Evidence from preclinical models for abnormalities within central circuits controlling fertility.
复制标题
多囊卵巢综合征中类固醇激素反馈受损：来自控制生育的中央回路异常的临床前模型的证据。
DOI：
10.1111/cen.14711
复制
发表时间：
2022
影响因子：
3.2
通讯作者：
Moore,AleishaM
中科院分区：
文献类型：
--
作者：
Moore,AleishaM
多囊卵巢综合征（PCOS）是世界范围内育龄妇女最常见的内分泌疾病和不孕原因。尽管无排卵、多囊卵巢形态和高雄激素分泌的诊断特征表明该综合征是卵巢功能障碍的结果，但控制生殖能力的中枢神经内分泌回路的改变可能导致PCOS症状。下丘脑中促性腺激素释放激素（GnRH）神经元对性类固醇激素负反馈抑制的抵抗导致脉冲性促性腺激素分泌频率加快，这反过来又驱动了该疾病的卵巢特征。由于GnRH神经元不表达类固醇激素受体，因此假设受损的负反馈发生在控制GnRH脉冲产生的上游网络中。本综述将讨论PCOS临床前动物模型的最新工作，用于剖析类固醇激素反馈受损的特定中枢机制。特别是，本综述将重点关注下丘脑弓状核中表达Kisspeptin、Neurokinin B和Dynorphin （KNDy细胞）或γ -氨基丁酸的神经元是雄激素介导的类固醇激素反馈损伤的靶点。最后，本文将探讨针对控制LH脉冲频率的神经元的治疗药物的发展，以缓解PCOS的临床症状。
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy and cause of infertility in women of reproductive age worldwide. Despite diagnostic features of anovulation, polycystic ovarian morphology, and high androgen secretion indicating the syndrome are the result of ovarian dysfunction, alterations to central neuroendocrine circuits that control reproductive capacity may drive PCOS symptoms. Resistance of gonadotrophin‐releasing hormone (GnRH) neurons in the hypothalamus to inhibition by sex steroid hormone‐negative feedback leads to a rapid frequency of pulsatile gonadotrophin secretion, which, in turn, drives the ovarian features of the disease. As GnRH neurons do not express steroid hormone receptors, impaired negative feedback is hypothesized to occur within an upstream network that controls GnRH pulse generation. This review will discuss the latest work from preclinical animal models of PCOS used to dissect the specific central mechanisms involved in impaired steroid hormone feedback. In particular, this review will focus on research that indicates neurons in the arcuate nucleus of the hypothalamus that express Kisspeptin, Neurokinin B and Dynorphin (KNDy cells) or γ‐aminobutyric acid are targets of androgen‐mediated impairment of steroid hormone feedback. Finally, this review will explore the development of therapeutic agents targeting neurons that control LH pulse frequency to resolve PCOS symptoms in the clinic.