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Phase-Dependent Shifting of the Adrenal Clock by Acute Stress-Induced ACTH

机译:急性应激诱导的ACTH的肾上腺时钟的相变

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The adrenal cortex has a molecular clock that generates circadian rhythms in glucocorticoid production, yet it is unclear how the clock responds to acute stress. We hypothesized that stress-induced ACTH provides a signal that phase shifts the adrenal clock. To assess whether acute stress phase shifts the adrenal clock in vivo in a phase-dependent manner, mPER2:LUC mice on a 12:12-h light:dark cycle underwent restraint stress for 15?min or no stress at zeitgeber time (ZT) 2 (early subjective day) or at ZT16 (early subjective night). Adrenal explants from mice stressed at ZT2 showed mPER2:LUC rhythms that were phase-advanced by ~2?h, whereas adrenals from mice stressed at ZT16 showed rhythms that were phase-delayed by ~2?h. The biphasic response was also observed in mice injected subcutaneously either with saline or with ACTH at ZT2 or ZT16. Blockade of the ACTH response with the glucocorticoid, dexamethasone, prevented restraint stress-induced phase shifts in the mPER2:LUC rhythm both at ZT2 and at ZT16. The finding that acute stress results in a phase-dependent shift in the adrenal mPER2:LUC rhythm that can be blocked by dexamethasone indicates that stress-induced effectors, including ACTH, act to phase shift the adrenal clock rhythm.
机译:肾上腺皮质有一个分子钟,可在糖皮质激素的产生中产生昼夜节律,但目前尚不清楚该钟如何响应急性应激。我们假设压力诱发的ACTH提供了一个使肾上腺时钟相移的信号。为了评估急性应激相是否以相位依赖的方式在体内改变肾上腺时钟,在12:12-h光:暗周期对mPER2:LUC小鼠进行了15?min的束缚应激或在Zeitgeber时间(ZT)无应激2(主日早)或ZT16(主日晚)。 ZT2应激的小鼠的肾上腺外植体显示mPER2:LUC节律提前约2?h,而ZT16应激的小鼠的肾上腺显示出时延约2?h。在ZT2或ZT16处皮下注射生理盐水或ACTH的小鼠中也观察到了双相反应。糖皮质激素地塞米松对ACTH反应的阻滞,可阻止在ZT2和ZT16处抑制应激诱导的mPER2:LUC节律相移。急性应激导致肾上腺mPER2:LUC节律发生相依​​性转变(可被地塞米松阻断)的发现表明,应激诱导的效应物(包括ACTH)起着使肾上腺钟律发生相变的作用。

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