A gradual adaptation to a shifted light-dark (LD) cycle is a key element of the circadian clock system and believed to be controlled by the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Endocrine factors have a strong influence on the regulation of the circadian clock network and alter acute photic responses of the SCN clock. In females, endocrine function depends on the stage of the ovarian cycle. So far, however, little is known about the effect of the estrous cycle on behavioral and molecular responses to shifts in the LD rhythm. Based on this, we investigated whether estrous state affects the kinetics of phase shift during jetlag in behavior, physiology, and molecular clock rhythms in the SCN and in peripheral tissues. Female mice exposed to an advanced LD phase at proestrous or metestrous showed different phase-shift kinetics, with proestrous females displaying accelerated adaptation in behavior and physiology. Constant darkness release experiments suggest that these fast phase shifts do not reflect resetting of the SCN pacemaker. Explant experiments on SCN, adrenal gland, and uterus confirmed this finding with proestrous females showing significantly faster clock phase shifts in peripheral tissues compared with the SCN. Together, these findings provide strong evidence for an accelerated adaptation of proestrous compared with metestrous females to new LD conditions that is accompanied by rapid behavioral, physiological, and molecular rhythm resetting. Not only do these findings open up a new avenue to understand the effect of estrous cycle on the clock network under changing environmental conditions but also imply a greater susceptibility in proestrous females.

逐渐适应转变的明暗 (LD) 周期是生物钟系统的关键要素，据信由中央昼夜节律起搏器视交叉上核控制(SCN)。内分泌因素对生物钟网络的调节有很强的影响，并改变 SCN 时钟的急性光反应。在女性中，内分泌功能取决于卵巢周期的阶段。然而，到目前为止，关于发情周期对 LD 节律变化的行为和分子反应的影响知之甚少。基于此，我们研究了发情状态是否会影响时差期间 SCN 和外周组织中行为、生理和分子钟节律的相移动力学。雌性小鼠在动情前或巨动时暴露于晚期 LD 阶段，表现出不同的相移动力学，动情前雌性在行为和生理上表现出加速适应。持续黑暗释放实验表明，这些快速相移并不反映 SCN 起搏器的重置。SCN、肾上腺和子宫的外植体实验证实了这一发现，与 SCN 相比，发情期女性在外周组织中显示出明显更快的时钟相移。总之，这些发现提供了强有力的证据，证明与动情雌性相比，动情雌性对新的 LD 条件的适应加速，伴随着快速的行为、生理和分子节律的重置。这些发现不仅为了解在不断变化的环境条件下发情周期对时钟网络的影响开辟了一条新途径，而且还暗示了发情期女性具有更大的易感性。和子宫证实了这一发现，与 SCN 相比，发情期女性在外周组织中显示出明显更快的时钟相移。总之，这些发现提供了强有力的证据，证明与动情雌性相比，动情雌性对新的 LD 条件的适应加速，伴随着快速的行为、生理和分子节律的重置。这些发现不仅为了解在不断变化的环境条件下发情周期对时钟网络的影响开辟了一条新途径，而且还暗示了发情期女性具有更大的易感性。和子宫证实了这一发现，与 SCN 相比，发情期女性在外周组织中显示出明显更快的时钟相移。总之，这些发现提供了强有力的证据，证明与动情雌性相比，动情雌性对新的 LD 条件的适应加速，伴随着快速的行为、生理和分子节律的重置。这些发现不仅为了解在不断变化的环境条件下发情周期对时钟网络的影响开辟了一条新途径，而且还暗示了发情期女性具有更大的易感性。这些发现提供了强有力的证据，证明与动情雌性相比，动情雌性对新的 LD 条件的适应加速，伴随着快速的行为、生理和分子节律的重置。这些发现不仅为了解在不断变化的环境条件下发情周期对时钟网络的影响开辟了一条新途径，而且还暗示了发情期女性具有更大的易感性。这些发现提供了强有力的证据，证明与动情雌性相比，动情雌性对新的 LD 条件的适应加速，伴随着快速的行为、生理和分子节律的重置。这些发现不仅为了解在不断变化的环境条件下发情周期对时钟网络的影响开辟了一条新途径，而且还暗示了发情期女性具有更大的易感性。