Influence of the estrous cycle on clock gene expression in reproductive tissues: effects of fluctuating ovarian steroid hormone levels.
Influence of the estrous cycle on clock gene expression in reproductive tissues: effects of fluctuating ovarian steroid hormone levels.
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DOI：
10.1016/j.steroids.2010.01.007
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发表时间：
2010-03
期刊：
影响因子：
2.7
通讯作者：
Block, Gene D.
中科院分区：
文献类型：
--
作者：
Nakamura, Takahiro J.;Sellix, Michael T.;Kudo, Takashi;Nakao, Nobuhiro;Yoshimura, Takashi;Ebihara, Shizufumi;Colwell, Christopher S.;Block, Gene D.
已知雌性啮齿动物的生理和行为的昼夜节律受到发情周期的影响。负责产生昼夜节律振荡的时钟基因在中枢神经系统和外围组织中广泛表达，包括组成生殖系统的那些组织。为了研究发情周期是否影响外周组织中时钟基因的表达节律，我们首先利用实时定量聚合酶链式反应(在体)和发光记录方法检测了周期大鼠生殖(子宫、卵巢)和非生殖(肝脏)组织中时钟基因(PER1，PER2，BMal1)的表达节律，以测量周期中PER2：：荧光素酶(PER2：：Luc)敲门小鼠(体外)组织外植体培养中PER2表达的昼夜节律。我们发现在体内三种组织和体外子宫中，Clock基因的表达都有显著的发情变化。我们还发现，外源雌激素和孕激素的应用改变了子宫中PER2：：Luc的表达节律。此外，我们测量了卵巢类固醇对人类乳腺癌细胞系(MCF-7细胞)时钟基因表达的影响，作为同时包含类固醇激素受体和时钟基因的内分泌细胞的模型。我们发现，孕酮，而不是雌激素，显著上调了MCF-7细胞中PER1、PER2和BMal1的表达。总之，我们的发现表明，生殖组织中生物钟的时间受到发情周期的影响，并表明类固醇激素水平的波动可能在一定程度上通过直接影响时钟基因表达的时间来起作用。
Circadian rhythms in physiology and behavior are known to be influenced by the estrous cycle in female rodents. The clock genes responsible for the generation of circadian oscillations are widely expressed both within the central nervous system and peripheral tissues, including those that comprise the reproductive system. To address whether the estrous cycle affects rhythms of clock gene expression in peripheral tissues, we first examined rhythms of clock gene expression (Per1, Per2, Bmal1) in reproductive (uterus, ovary) and non-reproductive (liver) tissues of cycling rats using quantitative real-time PCR (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 (ex vivo). We found significant estrous variations of clock gene expression in all three tissues in vivo, and in the uterus ex vivo. We also found that exogenous application of estrogen and progesterone altered rhythms of PER2::LUC expression in the uterus. In addition, we measured the effects of ovarian steroids on clock gene expression in a human breast cancer cell line (MCF-7 cells) as a model for endocrine cells that contain both the steroid hormone receptors and clock genes. We found that progesterone, but not estrogen, acutely up-regulated Per1, Per2, and Bmal1 expression in MCF-7 cells. Together, our findings demonstrate that the timing of the circadian clock in reproductive tissues is influenced by the estrous cycle and suggest that fluctuating steroid hormone levels may be responsible, in part, through direct effects on the timing of clock gene expression.
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