Estrogen receptor 1 modulates circadian rhythms in adult female mice
Estrogen receptor 1 modulates circadian rhythms in adult female mice
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DOI：
10.3109/07420528.2014.885528
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发表时间：
2014-01-01
影响因子：
2.8
通讯作者：
Mahoney, Megan M.
中科院分区：
文献类型：
--
作者：
Blattner, Margaret S.;Mahoney, Megan M.
雌二醇影响日常活动的水平和分布、自由奔跑期的持续时间以及对光脉冲的行为相反应。然而，雌二醇调节日常和昼夜节律的机制尚不完全清楚。我们测试了雌激素通过雌激素受体亚型1 （ESR1）的经典和“非经典”作用调节日常活动模式的假设。我们使用雌激素反应通路突变的雌性转基因小鼠；ESR1敲除（ERKO）小鼠和“非经典”雌激素受体敲入（NERKI）小鼠。NERKI小鼠的ESR1受体在雌激素反应元件结合域发生突变，只能通过“非经典”基因组和第二信使途径发挥作用。切除卵巢的雌性NERKI、ERKO和野生型（WT）小鼠被皮下注射低剂量或高剂量雌二醇胶囊，并与没有激素替代的对照组进行比较。我们测量了在明暗循环和持续黑暗中跑步的活动，以及在主观白天和夜间不同时间点对光脉冲的行为相反应。雌二醇增加了WT小鼠的平均每日轮跑，巩固了活动至暗期，缩短了内源性周期，但NERKI和ERKO小鼠没有。在所有接受雌二醇治疗的动物中，无论基因型如何，活动发生的时间都提前了，这表明这是一种与esr1无关的机制。我们认为雌二醇通过ESR1的经典作用改变周期、活动水平和活动分布，而ESR1独立的机制调节节律的阶段。
Estradiol influences the level and distribution of daily activity, the duration of the free-running period, and the behavioral phase response to light pulses. However, the mechanisms by which estradiol regulates daily and circadian rhythms are not fully understood. We tested the hypothesis that estrogens modulate daily activity patterns via both classical and "non-classical'' actions at the estrogen receptor subtype 1 (ESR1). We used female transgenic mice with mutations in their estrogen response pathways; ESR1 knock-out (ERKO) mice and "non-classical'' estrogen receptor knock-in (NERKI) mice. NERKI mice have an ESR1 receptor with a mutation in the estrogen-response-element binding domain, allowing only actions via "non-classical'' genomic and second messenger pathways. Ovariectomized female NERKI, ERKO, and wildtype (WT) mice were given a subcutaneous capsule with low-or high-dose estradiol and compared with counterparts with no hormone replacement. We measured wheel-running activity in a light: dark cycle and constant darkness, and the behavioral phase response to light pulses given at different points during the subjective day and night. Estradiol increased average daily wheel-running, consolidated activity to the dark phase, and shortened the endogenous period in WT, but not NERKI and ERKO mice. The timing of activity onset during entrainment was advanced in all estradiol-treated animals regardless of genotype suggesting an ESR1-independent mechanism. We propose that estradiol modifies period, activity level, and distribution of activity via classical actions of ESR1 whereas an ESR1 independent mechanism regulates the phase of rhythms.