Gonadal steroids and gender are risk factors for sleep disruptions and insomnia in women. However, the relationship between ovarian steroids and sleep is poorly understood. In rodent models, estradiol (E2) suppresses sleep in females suggesting that E2 may reduce homeostatic sleep need. The current study investigates whether E2 decreases sleep need and the potential mechanisms that govern E2 suppression of sleep. Our previous findings suggest that the median preoptic nucleus (MnPO) is a key nexus for E2 action on sleep. Using behavioral, neurochemical, and pharmacological approaches, we tested whether (1) E2 influenced the sleep homeostat and (2) E2 influenced adenosine signaling in the MnPO of adult female rats. In both unrestricted baseline sleep and recovery sleep from 6-h sleep deprivation, E2 significantly reduced nonrapid eye movement (NREM) sleep-delta power, NREM-slow wave activity (NREM-SWA, 0.5–4.0 Hz), and NREM-delta energy suggesting that E2 decreases homeostatic sleep need. However, coordinated with E2-induced changes in physiological markers of homeostatic sleep was a marked increase in MnPO extracellular adenosine (a molecular marker of homeostatic sleep need) during unrestricted and recovery sleep in E2-treated but not oil control animals. While these results seemed contradictory, systemically administered E2 blocked the ability of CGS-21680 (adenosine A2A receptor agonist) microinjected into the MnPO to increase NREM sleep suggesting that E2 may block adenosine signaling. Together, these findings provide evidence that E2 may attenuate the local effects of the A2A receptors in the MnPO, which in turn may underlie estrogenic suppression of sleep behavior as well as changes in homeostatic sleep need.

中文翻译：

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雌二醇影响成年雌性大鼠的腺苷能信号传导和非快速眼动睡眠需求

性腺类固醇和性别是女性睡眠中断和失眠的危险因素。然而，人们对卵巢类固醇和睡眠之间的关系知之甚少。在啮齿动物模型中，雌二醇 (E2) 会抑制女性的睡眠，这表明 E2 可能会减少稳态睡眠需求。目前的研究调查了 E2 是否会减少睡眠需求以及控制 E2 抑制睡眠的潜在机制。我们之前的研究结果表明，中位视前核 (MnPO) 是 E2 对睡眠的作用的关键纽带。使用行为学、神经化学和药理学方法，我们测试了 (1) E2 是否影响睡眠稳态和 (2) E2 是否影响成年雌性大鼠 MnPO 中的腺苷信号传导。在不受限制的基线睡眠和 6 小时睡眠剥夺后的恢复睡眠中，E2 显着降低了非快速眼动 (NREM) 睡眠-delta 功率、NREM-慢波活动 (NREM-SWA, 0.5–4.0 Hz) 和 NREM-delta 能量，表明 E2 降低了稳态睡眠需求。然而，与 E2 诱导的稳态睡眠生理标志物的变化相协调的是，在 E2 治疗但不是控油动物的无限制和恢复睡眠期间，MnPO 细胞外腺苷（一种稳态睡眠需求的分子标志物）显着增加。虽然这些结果似乎相互矛盾，但全身给药的 E2 阻断了微量注射到 MnPO 中的 CGS-21680（腺苷 A2A 受体激动剂）增加 NREM 睡眠的能力，这表明 E2 可能阻断腺苷信号传导。总之，这些发现提供了证据表明 E2 可以减弱 MnPO 中 A2A 受体的局部作用，