In vivo Circadian Rhythms in Gonadotropin-Releasing Hormone Neurons
In vivo Circadian Rhythms in Gonadotropin-Releasing Hormone Neurons
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DOI：
10.1159/000243163
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发表时间：
2010-01-01
影响因子：
4.1
通讯作者：
Tischkau, Shelley A.
中科院分区：
文献类型：
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作者：
Hickok, Jason R.;Tischkau, Shelley A.
虽然人们普遍认为生物钟为促黄体生成激素（LH）激增提供了一个定时信号，但对这一现象的机制解释仍不清楚。例如，已知昼夜运动输出周期kaput（时钟）突变小鼠严重抑制LH峰，但这种表型是否源于视交叉上核（SCN）的昼夜节律丧失或促性腺激素释放激素（GnRH）神经元的昼夜功能改变尚未解决。GnRH神经元可以在体外被刺激以昼夜节律周期循环，并且该周期的破坏扰乱GnRH十肽的分泌。我们发现，周期-2（PER 2）和脑肌肉Arnt样-1（BMAL 1）蛋白在体内GnRH群体中具有昼夜节律周期。PER 2和BMAL 1的表达都以24小时为周期振荡，PER 2在夜间达到峰值，BMAL 1在白天达到峰值。然而，该群体不像其他振荡组织那样同质，只有约50%的群体在授时因子时间4（ZT 4）共享BMAL 1的峰值表达水平，在ZT 16共享PER 2的峰值表达水平。此外，在GnRH-eGFP小鼠的活动节律中诱导相位延迟的光脉冲引起BMAL 1和PER 2的峰值表达水平的类似延迟。这些研究为天然GnRH神经元的功能性昼夜节律钟提供了直接证据，其相位与SCN的相位密切相关。版权所有（C）2009 S. Karger AG，巴塞尔
Although it is generally accepted that the circadian clock provides a timing signal for the luteinizing hormone (LH) surge, mechanistic explanations of this phenomenon remain underexplored. It is known, for example, that circadian locomotor output cycles kaput (clock) mutant mice have severely dampened LH surges, but whether this phenotype derives from a loss of circadian rhythmicity in the suprachiasmatic nucleus (SCN) or altered circadian function in gonadotropin-releasing hormone (GnRH) neurons has not been resolved. GnRH neurons can be stimulated to cycle with a circadian period in vitro and disruption of that cycle disturbs secretion of the GnRH decapeptide. We show that both period-2 (PER2) and brain muscle Arnt-like-1 (BMAL1) proteins cycle with a circadian period in the GnRH population in vivo. PER2 and BMAL1 expression both oscillate with a 24-hour period, with PER2 peaking during the night and BMAL1 peaking during the day. The population, however, is not as homogeneous as other oscillatory tissues with only about 50% of the population sharing peak expression levels of BMAL1 at zeitgeber time 4 (ZT4) and PER2 at ZT16. Further, a light pulse that induced a phase delay in the activity rhythm of the GnRH-eGFP mice caused a similar delay in peak expression levels of BMAL1 and PER2. These studies provide direct evidence for a functional circadian clock in native GnRH neurons with a phase that closely follows that of the SCN. Copyright (C) 2009 S. Karger AG, Basel