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

Area of Science:

• Chronobiology
• Urology
• Endocrinology

Background:

• Peripheral clocks regulate organ function and are synchronized by molecular and behavioral cues.
• The specific signals that entrain the bladder clock, however, have remained largely unknown.

Purpose of the Study:

• To investigate the role of glucocorticoids as potential zeitgebers for the mammalian bladder clock.
• To determine if glucocorticoid signaling influences the diurnal rhythm of bladder function, specifically voiding patterns.

Main Methods:

• Utilized a human urothelial cell line engineered with a pBmal1-dLuc reporter to assess gene expression changes following cortisol treatment.
• Conducted in vivo studies using mice, involving bilateral adrenalectomy and timed administration of corticosterone to evaluate bladder clock gene expression and voiding rhythms.
• Monitored diurnal activity rhythms alongside voided volume per micturition to differentiate clock entrainment effects.

Main Results:

• Cortisol treatment induced significant shifts in gene expression within the human urothelial cell line.
• In vivo, corticosterone administration shifted bladder clock gene expression, particularly in adrenalectomized mice.
• Adrenalectomized mice receiving corticosterone exhibited altered diurnal rhythms in voided volume per micturition, while general activity rhythms remained intact.

Conclusions:

• Diurnal glucocorticoid signaling acts as a potent zeitgeber for the bladder clock, overriding other entrainment factors.
• Glucocorticoid signaling is essential for coordinating the diurnal rhythm of voided volume per micturition.
• These findings highlight a critical link between endocrine rhythms and bladder physiology.