Control 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 pBmal1-dLuc human urothelial cell line showed significant shifts in gene expression after cortisol treatment while, in vivo, rhythmic bladder clock gene expression was not influenced by bilateral-adrenalectomy (ADx) but shifted 4 hours forward by corticosterone administration at the inactive phase (CORT). Moreover, the bladder clock shifted 8-12 hours in ADx+CORT mice. These mice saw decreases in the diurnal rhythm of volume voided per micturition, while maintaining diurnal activity rhythm. These results indicate that the diurnal rhythm of glucocorticoid signaling is a zeitgeber that overcomes other entrainment factors for the bladder clock and coordinates the diurnal rhythm of volume voided per micturition. (145 words) Examination of changes over time in total bladder RNA in mice with bilateral adrenalectomy and corticosterone administration or contol.