Le Minh N, Damiola F, Tronche F, Schütz G, Schibler U
Département de Biologie Moléculaire, Sciences II, Université de Genève, 30 Quai Ernest Ansermet, CH-1211 Genève, Switzerland.
EMBO J. 2001 Dec 17;20(24):7128-36. doi: 10.1093/emboj/20.24.7128.
The circadian timing system in mammals is composed of a master pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus and slave clocks in most peripheral cell types. The phase of peripheral clocks can be completely uncoupled from the SCN pacemaker by restricted feeding. Thus, feeding time, while not affecting the phase of the SCN pacemaker, is a dominant Zeitgeber for peripheral circadian oscillators. Here we show that the phase resetting in peripheral clocks of nocturnal mice is slow when feeding time is changed from night to day and rapid when switched back from day to night. Unexpectedly, the inertia in daytime feeding-induced phase resetting of circadian gene expression in liver and kidney is not an intrinsic property of peripheral oscillators, but is caused by glucocorticoid signaling. Thus, glucocorticoid hormones inhibit the uncoupling of peripheral and central circadian oscillators by altered feeding time.
哺乳动物的昼夜节律系统由下丘脑视交叉上核（SCN）中的主起搏器和大多数外周细胞类型中的从属时钟组成。通过限制进食，外周时钟的相位可以与SCN起搏器完全解耦。因此，进食时间虽然不影响SCN起搏器的相位，但却是外周昼夜节律振荡器的主要授时因子。在这里，我们表明，当进食时间从夜间改为白天时，夜行性小鼠外周时钟的相位重置很慢，而从白天切换回夜间时则很快。出乎意料的是，肝脏和肾脏中昼夜节律基因表达在白天进食诱导的相位重置中的惯性不是外周振荡器的固有特性，而是由糖皮质激素信号传导引起的。因此，糖皮质激素通过改变进食时间来抑制外周和中枢昼夜节律振荡器的解耦。
