Enzyme could explain link between metabolic disease and PCOS

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US scientists have discovered a new link between increased male hormones and metabolic disease in people with polycystic ovary syndrome (PCOS). An enzyme that activates male hormone in the fat tissue of women with PCOS has been identified which could raise the risk of other metabolic health complications, including type 2 diabetes and fatty liver disease. Women with PCOS often have higher levels of male hormones circulating in the blood, and this study has, for the first time, showed that hormones in abdominal fat tissue far exceed those measured in their blood. The enzyme responsible for this is AKR1C3, which is increased in fat tissue of women with PCOS and, according to researchers from the University of Birmingham, "causes increased activation of male hormones". Professor Wiebke Arlt, Director of the Institute of Metabolism and Systems Research at the University of Birmingham, said this led to "increased activation of male hormones, which we observed to lead to increased build-up of lipid droplets in the fat cells and, eventually, to fatty acid overspill into the circulation." Arlt explained that the overspill affected how cells responded to insulin. Fat cells become less responsive and greater levels of insulin are produced. This increased insulin then leads to even higher levels of AKR1C3. "This vicious circle drives complications like fatty liver disease, which recently have been shown to be more common in women with PCOS," said Arlt. Dr Michael O'Reilly, also from the University of Birmingham, added: "This study is particularly exciting because it highlights the role that body fat plays in generating excess male hormones in PCOS women, which then act locally to disrupt the ability of the body's fat to store lipid effectively. "Finding a new treatment that reduces the risk of diabetes and fatty liver disease in women with PCOS would bring relief to millions of patients." The study has been published in The Journal of Clinical Endocrinology &Metabolism.

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