Glucocorticoids May Reset Biological Clocks

Biological clocks located in peripheral white blood cells can be synchronized through administration of glucocorticoids, opening up new therapeutic avenues for improving the synchronization of the body’s various biological clocks, according to a new study.

Physiological changes over the course of a day are regulated by a circadian system composed of a central clock located deep within the center of the brain and multiple clocks located in different parts of the body.

“These results lead us to believe that we may one day be able to use a combined therapy that targets the central clock (inverting work schedules, administering controlled light therapy) with a pharmacological treatment that targets the peripheral clocks to ensure that all clocks are adjusted,”  said lead author Diane B. Boivin, MD, PhD, Professor in the Faculty of Medicine at McGill University and the Founder/Director of the Centre for Study and Treatment of Circadian Rhythms of the Douglas Mental Health University Institute in Montreal.

In previous studies, Dr Boivin and her team showed that desynchronized circadian clocks disrupt the sleep, performance, and cardiac parameters of night-shift workers. The researchers also showed that exposing workers to bright light at night or adjusting work schedules can improve the synchronization of the central biological clock to their atypical work schedule.

“A single therapy can’t address the disruptions that occur in all biological clocks,” stated Dr Boivin. “For example, when used incorrectly, light therapy can even aggravate the situation.”

Clock genes drive biological clocks, and these genes are active in all body organs. Animal studies have shown that the central biological clock in the brain sends signals to the clocks in other organs. Glucocorticoids appear to play a central role in transmitting these signals. This is the first study to demonstrate that glucocorticoids play this role in humans, the researchers stated.

They studied the rhythmic expression of clock genes in white blood cells of 16 healthy volunteers to see how the volunteers adjusted to glucocorticoids administered in the late afternoon.

The results show that 20 mg of hydrocortisone taken orally acutely increased gene expression in peripheral blood mononuclear cell (PBMC) peripheral clocks. After 6 days of hydrocortisone administration, the phases of central markers were not affected; however, expression of 2 genes in PBMCs were shifted by about 9.5 to 11.5 hours.

This suggests that biological rhythms may play a role in controlling immune function in night-shift workers, the investigators stated.

The new research opens the door to innovative therapies that adjust circadian rhythms in inverted sleep schedules, combining synchronizing agents for the central and peripheral clocks.

This has possible applications for travelers, night-shift workers, patients who are experiencing sleep disorders and circadian rhythm disorders, and persons with various psychiatric disorders, they stated.

“At this stage, we are not recommending the use of glucocorticoids to adjust the rhythms of night-shift workers, as there could be medical risks,” Dr Boivin said.

The researchers published their results online December 12, 2014 in The FASEB Journal.