New insights into corticosteroid-binding globulin and glucocorticoid delivery

Corticosteroid-binding globulin (CBG) binds cortisol with high affinity and facilitates its transport in the blood. A recent discovery suggests that CBG may have a role beyond that of a simple transport carrier protein. CBG functions as a protein thermocouple that is exquisitely sensitive to temperature change, releasing cortisol in response to increasing temperatures within the human physiological range. It is also expressed in the human hypothalamus and cerebrospinal fluid, while in the rodent it is also found in other intracellular neuronal locations, suggesting a role in regulating access of glucocorticoids to their receptors in the CNS. Genetic variants of CBG have been detected in man and have been associated with fatigue-pain syndromes and hypotension, again suggesting a potential effect of CBG on the access of cortisol to brain glucocorticoid receptors. These new findings provide the basis for a novel concept of the mechanisms through which the body regulates access of glucocorticoids to the brain and other tissues of the body.

▶Temperature-responsive release of cortisol from CBG—a protein thermocouple. ▶CBG function beyond that of a simple transport protein—current evidence. ▶Neuronal CBG expression—potential role in modulating glucocorticoid exposure to the CNS.