A clinical study has found a biomarker for glucocorticoid action that can be used to develop tests to help clinicians customize treatments
Researchers have uncovered pathways involved in the body’s response to glucocorticoid treatments and identified a new biological marker that could be used to monitor how these drugs work in patients, according to a clinical study published today in eLife.
A more reliable indicator of an individual’s response to glucocorticoid drugs could be used to develop a clinically applicable test that can help tailor treatments and reduce potential side effects.
Glucocorticoids, like cortisol, are a type of hormone that has major roles in the body’s response to stress. Glucocorticoid medications are one of the most commonly prescribed treatments for a range of conditions, including patients whose adrenal glands cannot produce enough cortisol. The effects of glucocorticoids are complex, which means that the level of cortisol in the blood does not reliably reflect what is happening in the tissues. This makes it difficult for medical professionals to know how to design treatments.
First author Demetrius Chantzikristus, chief physician in the Department of Endocrinology and Diabetes – explains – “Side effects of glucocorticosteroids are common in patients, indicating that current methods of monitoring their work, which typically focus on clinical response or disease activity,” explains Metabolism, University Hospital Sahlgrenska, Sweden. “We wanted to find a type of biomarker that could be measured to monitor glucocorticoid action in individuals, in the hope that this would help clinicians understand how best to treat patients.”
The team studied patients with Addison’s disease who lacked the ability to make their own cortisol. This allowed them to compare activity in the same patient’s tissues when their cortisol levels were low and when they were restored by glucocorticoid treatments, which helps account for differences between individuals.
Instead of focusing solely on the metabolic products associated with exposure to glucocorticoids, they also looked at gene expression and microRNAs in patients using new computational methods developed in collaboration with Dr. Adam Stevens at the University of Manchester, UK. MicroRNAs are short strands of RNA that can regulate the expression of genes by interfering with protein production. The team analyzed these various factors in blood cells and body fats, which are an important metabolic tissue, as the patients’ cortisol levels were altered, and revealed the close relationships between the different elements involved in the action of glucocorticoids.
Among the elements identified, the miR-122-5p microRNA is closely related to genes and metabolites regulated by glucocorticoid treatments. To test this association, the team looked at levels of miR-122-5p in the blood of patients exposed to different glucocorticoid levels from three independent studies and found the same pattern, supporting the idea that this microRNA could be a useful biological marker for glucocorticoid action.
Lead author Gudmundur Johansson, professor in the Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Sweden, concludes that “this potential biomarker can now be investigated in larger groups of patients with the goal of developing a clinically applicable test”. “Our work has also increased our understanding of the action of glucocorticoids, which may help reveal their role in many common diseases such as diabetes, obesity, and cardiovascular disease.”
This study was a collaborative effort between researchers at the universities of Manchester (UK), Edinburgh (UK), Copenhagen (Denmark) and Gothenburg (Sweden), as well as the University of Newcastle (UK) and University Hospital Sahlgrenska (Sweden).
Emily Packer, Director of Media Relations
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Full list of sponsors for this study:
Vetenskapsrådet, Swedish Federal Government under the LUA / ALF Agreement, Swedish Endocrinology Association, Gutenberg Medical Association, Wellcome Trust, Medical Research Council, Chief Scientist Office, Eva Madura Foundation, Rigshospitalet, Danish Rheumatology Association
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