The effect of circadian rhythm on prolactin/PRLR-mediated intracellular signaling profiles in vivo and in vitro

The circadian molecular Clock is an internal time-keeping system, which regulates various physiological processes. The circadian Clock may be involved in all biological processes. The circadian Clock is closely related to prolactin's activities. However, until now, the effect of circadian Clock dysregulation on PRL's bioactivities remains unclear. Clock protein is an essential component in circadian Clock and necessary for Clock function. Therefore, Clock gene knockout mice (CLOCK-/- mice) was used to explore the effect of circadian Clock dysfunction on PRL's activities. The in vitro and in vivo experimental results showed that PRLR-mediated signaling was significantly down-regulated. PRL-induced JAK2-STAT5 signaling in Clock(-/-) mice was significantly decreased compared to control mice in vivo. In vitro, PRL/PRLR-mediated signaling in mammary epithelial cell that Clock was knocked down by siRNA was significantly down-regulated compared to control cells. Mechanistically, the expression levels of negative regulatory molecule (the suppressor of cytokine signaling (SOCS) was upregulated in vitro and in vivo, which may be one of the factors that causes the PRL-signaling downregulation. Taken together, the current work indicates that the circadian Clock affects the PRL's activities. This finding lays the foundation for studying the relationship between the circadian Clock and PRL's biological activities.

Automated summary

The study reveals that the circadian Clock affects the activities of PRL. Using Clock gene knockout mice, researchers found that PRL-induced signaling was significantly reduced in Clock(-/-) mice, both in vitro and in vivo. The upregulation of negative regulatory molecule SOCS may be one of the factors causing the downregulation of PRL signaling.