Centre for Neuroendocrinology and Department of Physiology, University of Otago, Dunedin, New Zealand.
Brain Health Research Institute and Department of Biological Sciences, Kent State University, Kent, OH, United States.
Front Endocrinol (Lausanne). 2022 Aug 5;13:951344. doi: 10.3389/fendo.2022.951344. eCollection 2022.
Polycystic ovary syndrome (PCOS) is associated with elevated androgen and luteinizing hormone (LH) secretion and with oligo/anovulation. Evidence indicates that elevated androgens impair sex steroid hormone feedback regulation of pulsatile LH secretion. Hyperandrogenemia in PCOS may also disrupt the preovulatory LH surge. The mechanisms through which this might occur, however, are not fully understood. Kisspeptin (KISS1) neurons of the rostral periventricular area of the third ventricle (RP3V) convey hormonal cues to gonadotropin-releasing hormone (GnRH) neurons. In rodents, the preovulatory surge is triggered by these hormonal cues and coincident timing signals from the central circadian clock in the suprachiasmatic nucleus (SCN). Timing signals are relayed to GnRH neurons, in part, projections from SCN arginine-vasopressin (AVP) neurons to RP3V neurons. Because rodent SCN cells express androgen receptors (AR), we hypothesized that these circuits are impaired by elevated androgens in a mouse model of PCOS. In prenatally androgen-treated (PNA) female mice, SCN expression was significantly increased compared to that found in prenatally vehicle-treated mice. A similar trend was seen in the number of -positive SCN cells expressing . In the RP3V, the number of kisspeptin neurons was preserved. Anterograde tract-tracing, however, revealed reduced SCN neuron projections to the RP3V and a significantly lower proportion of RP3V neurons with close appositions from SCN fibers. Functional assessments showed, on the other hand, that RP3V neuron responses to AVP were maintained in PNA mice. These findings indicate that PNA changes some of the neural circuits that regulate the preovulatory surge. These impairments might contribute to ovulatory dysfunction in PNA mice modeling PCOS.
多囊卵巢综合征（PCOS）与雄激素和黄体生成素（LH）分泌升高以及少/无排卵有关。有证据表明，升高的雄激素会损害甾体激素对 LH 脉冲分泌的反馈调节。PCOS 中的高雄激素血症也可能破坏排卵前 LH 激增。然而，这种情况发生的机制尚不完全清楚。第三脑室前室周区（RP3V）的 kisspeptin（KISS1）神经元向促性腺激素释放激素（GnRH）神经元传递激素信号。在啮齿动物中，促性腺激素释放激素（GnRH）神经元受这些激素信号和来自视交叉上核（SCN）的中央生物钟的同步定时信号的触发，触发排卵前激增。定时信号部分通过 SCN 精氨酸加压素（AVP）神经元向 RP3V 神经元的投射传递到 GnRH 神经元。由于啮齿动物 SCN 细胞表达雄激素受体（AR），我们假设这些环路在 PCOS 的小鼠模型中被升高的雄激素所损害。在产前雄激素处理（PNA）的雌性小鼠中，与产前载体处理的小鼠相比，SCN 的表达显著增加。在表达 的 SCN 细胞中也观察到类似的趋势。在 RP3V 中， kisspeptin 神经元的数量保持不变。然而，顺行追踪显示 SCN 神经元向 RP3V 的投射减少，并且具有 SCN 纤维紧密贴合的 RP3V 神经元的比例明显降低。另一方面，功能评估显示，在 PNA 小鼠中，RP3V 神经元对 AVP 的反应得以维持。这些发现表明，PNA 改变了一些调节排卵前激增的神经环路。这些损伤可能导致 PNA 模拟 PCOS 的小鼠的排卵功能障碍。
