Corticosteroid-binding globulin, also referred to as transcortin or SerpinA6, is produced and secreted primarily by hepatocytes in the liver and is considered a negative acute phase protein. It contains a single binding site for glucocorticoids and progesterone, both of which bind with high affinity, with an estimated 80�C90% of endogenous GCs bound to CBG. Although its main function is to transport and modulate the bioavailability of these steroids, the role of CBG is believed to extend to more than a carrier protein. It has been proposed that CBG acts as a reservoir for GCs and CCG 50014 directly transports and releases these steroid hormones at target tissues during inflammation. According to the free hormone hypothesis, only the free fraction of steroid hormone is biologically active and able to diffuse across the plasma membrane of target tissues. The ratio between free and bound steroids depends on the number of binding sites and the affinity for the binding sites. This implies that any changes in the Clopidol levels of CBG would modify the distribution of steroids to target tissues and indeed, free corticosterone levels in CBG knockout mice have been reported to be 10-times higher than in wild type mice. Several factors influence CBG production including a variety of stressors and hormones. GCs are the major hormone secreted during stress and they mediate their biological effect through binding to the glucocorticoid receptor whereby it is able to modulate gene expression. GCs also regulate the level of their transport protein, CBG, in a negative feedback loop. In humans, plasma levels of CBG are suppressed during prolonged exposure to GCs, whether endogenous, as in Cushing��s syndrome, or exogenous, as during administration of synthetic GCs. A number of studies in rats also indicate that physiological and physical stressors down-regulate CBG production. Furthermore, the dramatic fall of CBG levels during stress, with concomitant substantial increases in free GC levels, merits its classification as a negative APP. In humans, for example, CBG levels are dramatically decreased during inflammation and this drastic decrease in CBG levels has been associated with impaired immune function.