Abstract
Corticosteroid-binding globulin (CBG, transcortin) is the primary cortisol binding
protein. It is a non-inhibitory serine protease inhibitor, capable of conformational change
from a high cortisol-binding affinity form to a low affinity form upon cleavage of
its reactive centre loop by various proteases, such as neutrophil elastase. The burgeoning
inflammatory role of CBG applies to acute, severe inflammation where depletion is
associated with mortality, and to chronic inflammation where defects in cortisol delivery
may perpetuate inflammation. Naturally occurring human mutations influence a wide
range of CBG properties and point toward a role in hitherto unexplained chronic musculoskeletal
pain and fatigue disorders as well as potentially affecting fertility outcomes including
offspring gender. In vitro and knock-out animal models of CBG propose a role for CBG
in cortisol transport to the brain, providing a foundation for understanding the human
observations in those with CBG mutations and sex differences in stress-related mood
and behaviour. Finally, CBG measurement has a practical role in the estimation of
free cortisol, useful in clinical circumstances where CBG levels or cortisol binding
affinity is reduced. Taken together, novel data suggest a role for cortisol in targeted
cortisol delivery, with implications in acute and chronic inflammation, as well as
roles in metabolism and neurocognitive function, implying that CBG is a multifaceted
component in the mechanisms of hypothalamic-pituitary-adrenal axis related homeostasis.
Key words
cortisol - high-affinity CBG - low-affinity CBG - inflammation
