Carbonyl reductase 1 and 20β-dihydrocortisol: a novel glucocorticoid metabolism pathway in the pathogenesis of mineralcorticoid activation in obesity

Glucocorticoids, such as cortisol, are hormones which regulate stress, inflammation, infection and blood pressure. Levels of glucocorticoids are tightly regulated by the brain and adrenal gland but also by individual organs. High glucocorticoid levels are associated with conditions such as obesity and high blood pressure, which are risk factors for heart attacks and strokes. Glucocorticoids are broken down in tissues by several metabolic pathways and this normally results in an inactive product.

We have discovered a pathway, called CBR1, which breaks down glucocorticoids into an active product which has strong effects on the receptors regulating blood pressure and salt balance. The enzyme responsible for this pathway is found in almost every tissue of the body. The pathway is up-regulated in obesity and there is evidence that it may be important in other diseases such as liver disease and cancer. Food and supplements may interfere with its action.

We aim to ascertain the role of this pathway in health and determine its importance in diseases such as obesity and high blood pressure.