Tissue-specific control of cortisol versus corticosterone in humans

Human adrenal glands secrete both cortisol and corticosterone. High cortisol levels in blood cause Cushing's syndrome, with obesity and accelerated cardiovascular disease, while low levels cause Addison's disease. Professor Walker's research has shown that cardiometabolic risk factors in the population are associated with more subtle elevation in cortisol levels in both blood and tissue. However, any contribution of corticosterone in humans has been neglected to date. During this award, using the experimental medicine toolkit that his group has developed to study steroid physiology in vivo in humans, Professor Walker will extend recent discoveries that blood and tissue levels of cortisol and corticosterone are controlled independently, and establish the consequences for steroid signalling in adipose tissue in obesity. The programme will include proof of concept for a new therapeutic approach to improve metabolic control in patients with adrenal insufficiency.