08:07pm Sunday 23 September 2018

Body clock link to steroids discovered

Scientists at The Universities of Manchester and Leeds have discovered that the time of day influences the way mice respond to steroids.

Professor David Ray, from The University of Manchester, led the research which found that out of 752 genes which regulate lungs in mice, 230 genes work only in the day and only 197 at night.

And in the liver, where doctors have long thought that steroids are influential for many side effects, 1,702 genes regulate the organ in the day and a mere 299 at night in mice.

The research could one day have important implications on the way steroids – one of the most common drugs in medicine – are prescribed.

Published in the Journal of Clinical Investigation, the study is funded by the Wellcome Trust and the National Institutes of Health in the United States.

When Reverbα – a molecule that controls the time of day effect is removed, the liver flips its genes so that more genes are regulated at night than during the day.

The removal of Reverbα also seemed to have a protective effect against the build up of fat in the liver – known as fatty liver.

Steroids are the most potent anti-inflammatory agent known to medicine. They are widely used and are very effective and used to treat a wide range of conditions. We can’t yet say that this research confirms that taking steroids at different times of the day will impact on things like side effects. But this is clearly an exciting advance in the way we understand how steroids work.

Professor David Ray

And that, says Professor Ray, could be important as daytime genes regulate glucose metabolism whereas night genes regulate fat metabolism.

Fatty liver is common, leads to diabetes, and can result in serious liver damage, including cirrhosis, if it progresses.

Professor Ray said: “Steroids are the most potent anti-inflammatory agent known to medicine. They are widely used and are very effective and used to treat a wide range of conditions.

“We can’t yet say that this research confirms that taking steroids at different times of the day will impact on things like side effects.

“But this is clearly an exciting advance in the way we understand how steroids work.”

He added: “There are experimental drugs which have been targeting Reverbα in animals.

“But now we hope to move on to measuring effectiveness and side effects on human tissue.”

REV-ERBα Couples the Circadian Clock to Hepatic Glucocorticoid Action is published in the Journal of Clinical Investigation.

 

The University of Manchester

 


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