Progesterone, but not estradiol, synchronizes circadian oscillator in the uterus endometrial stromal cells
Progesterone, but not estradiol, synchronizes circadian oscillator in the uterus endometrial stromal cells
复制标题
DOI：
10.1007/s11010-008-9981-4
复制
发表时间：
2008
影响因子：
4.3
通讯作者：
Masami Hirata;Pei-jian He;N. Shibuya;M. Uchikawa;N. Yamauchi;S. Hashimoto;M. Hattori
中科院分区：
文献类型：
--
作者：
Masami Hirata;Pei-jian He;N. Shibuya;M. Uchikawa;N. Yamauchi;S. Hashimoto;M. Hattori
昼夜节律振荡器在视交叉上核内产生，并在许多外周组织中同步昼夜节律时钟。分子基础是由形成转录和翻译反馈环的许多基因和蛋白质组成的。这种分子振荡器也适用于周围组织，包括子宫。虽然卵巢类固醇调节子宫内膜间质细胞的功能，但它对昼夜节律的调节尚不清楚。在这里，我们研究了雌二醇(E_2)和孕酮(P_4)调节基质细胞昼夜节律振荡器的可能性。本研究利用构建的PER2启动子失稳荧光素酶(PER2-dLUC)基因转基因大鼠，建立Per2-dLUC振荡实时监测系统。经地塞米松处理后，间质细胞呈现恒定的Per2-dLuc振荡，提示昼夜节律振荡器起作用。然而，在体内注射人绒毛膜促性腺激素(HCG)后，这种昼夜节律振荡器被扰乱，尽管在hCG后4天，它被改变为有节奏的模式。用P4慢性处理后，未成熟和妊娠大鼠的间质细胞产生恒定的Per2-dLuc振荡，而E2不促进这种节律性的Per2-dLuc振荡。总体而言，P4通过发条系统的转录和翻译反馈环同步子宫内膜间质细胞的昼夜节律振荡器。
The circadian oscillator is generated within the suprachiasmatic nuclei and synchronizes circadian clocks in numerous peripheral tissues. The molecular basis is composed of a number of genes and proteins that form transcriptional and translational feedback loops. Such molecular oscillators are also operative in peripheral tissues, including in the uterus. Although ovarian steroids regulate the function of uterine endometrial stromal cells, the modulation of ovarian steroids on the circadian rhythms remains unknown. Here we investigate the possibility that estradiol (E2) and progesterone (P4) modulate the circadian oscillator of the stromal cells. The study using transgenic rats constructed withPeriod2(Per2) promoter-destabilized luciferase (Per2-dLuc) gene, with the real-time monitoring system ofPer2-dLucoscillation. The stromal cells displayed constantPer2-dLucoscillation after treatment with dexamethasone, suggesting that the circadian oscillator is operative. However, the circadian oscillator was disrupted by in vivo administration of human chorionic gonadotropin (hCG) following equine chorionic gonadotropin (eCG), although it was altered into a rhythmic pattern 4 days later following hCG. Chronic treatment with P4 induced constantPer2-dLucoscillation in the stromal cells from eCG-treated immature and pregnant rats, whereas E2 did not promote such a rhythmicPer2-dLucoscillation. Collectively, P4 synchronizes the circadian oscillator of the uterus endometrial stromal cells through transcriptional and translational feedback loops of the clockwork system.