Grant: Operating Grant

Cortisol is a natural steroid hormone that controls the growth and development of most of our vital organs, and it helps us deal with stress, fight off infections, and recover after illness. It is also used extensively as a drug that is commonly known as hydrocortisone. The way cortisol acts as a hormone inside cells has been well studied but how it gets to these cells is less well understood. Our studies of the plasma binding protein for cortisol, known as Corticosteroid Binding Globulin or CBG, have shown us that - in addition to transporting cortisol in the blood - CBG influences how cortisol gains access to specific cells during normal development and diseases like inflammation. There is evidence that defects in the production or function of CBG in humans are associated with hypotension, chronic fatigue, and our ability to respond to acute inflammation. We propose that a greater understanding of how CBG is produced and functions, and how CBG deficiencies might contribute to disease states, could improve and personalize steroid and other drug treatment regimens, especially during life-threatening events. With this as the ultimate goal, our priority is to: (1) Further define the structure and function of CBG and to use this knowledge to design novel therapeutic strategies; (2) delineate how plasma CBG production is regulated under both normal and pathological conditions, and (3) define how abnormalities in human CBG production or function contribute to adverse clinical outcomes.