Neural mechanisms of gonadal steroid hormone effectsin circadian rhythmicity

女性患有一系列睡眠障碍，其中失眠和睡眠过度尤为常见。在许多情况下，这些睡眠障碍与内分泌变化密切相关，包括月经，怀孕和更年期。长期以来，人们一直推测，在此期间发生的性腺类固醇激素水平的变化与这些睡眠-觉醒障碍密切相关。我们的目标是确定性腺类固醇的神经机制，特别是雌激素驱动的昼夜节律系统的变化。在本研究中，我们试图确定雌激素直接影响并导致雌性啮齿动物昼夜行为节律改变的雌激素敏感振荡器。我们使用免疫组织化学（体内）和发光记录方法检测大脑中几个靶区域的时钟基因（PER 2）表达的节律，以测量来自循环PER 2：：LUCIFERASE（PER 2：：LUC）敲入小鼠（体外）的组织外植体培养物中PER 2表达的昼夜节律。我们发现，雌激素治疗直接影响下丘脑视前区（POA）的PER 2：：LUC节律。最终，我们的研究结果将为女性睡眠障碍提供新的治疗方法，并改善女性在整个生命周期中的生活质量。

Women suffer from a range of sleep disorders with insomnia and hypersomnia being particularly common. In many cases, these sleep disorders are tightly associated with endocrine changes including menstruation, pregnancy, and menopause. It has been long speculated that variations of gonadalsteroid hormone levels that occur during this times are closely related to these sleep-wake disturbances. Our goalisto determine the neural mechanisms that underlie gonadal steroids, especially, estrogen driven changes in the circadian timing system. In this study, we tried to identify estrogen sensitive oscillator(s) which estrogen directly influences and lead to change circadian behavioral rhythm in female rodents. We examined rhythms of clock gene expression(PER2) in several target regions in the brainusing immunohistochemistry(in vivo) and luminescent recording methods to measure circadian rhythms of PER2 expression in tissue explant cultures from cycling PER2 :: LUCIFERASE(PER2 :: LUC) knockin mice(in vitro). We found that PER2 :: LUC rhythm in preoptic area(POA) of the hypothalamus was directly influenced by estrogen treatments. Ultimately, our findings will result in new therapeutic approaches for sleep disorders in women and improve the quality of life for women throughout their lifecycle.