糖皮质激素协调小鼠膀胱外周时钟和昼夜排尿模式。

Glucocorticoids coordinate the bladder peripheral clock and diurnal micturition pattern in mice.

机构信息

Department of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Department of Urology, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan.

出版信息

Commun Biol. 2023 Jan 21;6(1):81. doi: 10.1038/s42003-023-04464-3.

Abstract

Peripheral clocks function to regulate each organ and are synchronized though various molecular and behavioral signals. However, signals that entrain the bladder clock remain elusive. Here, we show that glucocorticoids are a key cue for the bladder clock in vitro and in vivo. A pBmal1-dLuc human urothelial cell-line showed significant shifts in gene expression after cortisol treatment. In vivo, rhythmic bladder clock gene expression was unchanged by bilateral adrenalectomy but shifted 4 h forward by corticosterone administration at the inactive phase. Moreover, the bladder clock shifted 8-12 h in mice that underwent both bilateral adrenalectomy and corticosterone administration at the inactive phase. These mice showed decreases in the diurnal rhythm of volume voided per micturition, while maintaining diurnal activity rhythms. These results indicate that the diurnal rhythm of glucocorticoid signaling is a zeitgeber that overcomes other bladder clock entrainment factors and coordinates the diurnal rhythm of volume voided per micturition.

摘要

外周时钟的功能是调节各个器官,并通过各种分子和行为信号进行同步。然而,使膀胱时钟同步的信号仍然难以捉摸。在这里,我们表明糖皮质激素是体外和体内膀胱时钟的关键线索。pBmal1-dLuc 人尿路上皮细胞系在皮质醇处理后显示出基因表达的显著变化。在体内,双侧肾上腺切除术不会改变节律性膀胱时钟基因表达,但在非活动期给予皮质酮会使其向前移动 4 小时。此外,在非活动期同时进行双侧肾上腺切除术和皮质酮给药的小鼠中,膀胱时钟会移动 8-12 小时。这些小鼠每排尿量的昼夜节律减少,同时保持昼夜活动节律。这些结果表明,糖皮质激素信号的昼夜节律是一个 Zeitgeber,它克服了其他膀胱时钟同步因素,并协调了每排尿量的昼夜节律。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b1b/9867708/3ca2687a2352/42003_2023_4464_Fig1_HTML.jpg

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