Coordination of bladder peripheral clock and diurnal micturition pattern by glucocorticoids

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 p Bmal1 -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 hours forward by corticosterone administration at the inactive phase. Moreover, the bladder clock shifted 8–12 hours in mice that underwent both bilateral adrenalectomy and corticosterone administration at the inactive phase. These mice saw 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.