New roles for corticosteroid binding globulin and opposite expression profiles in lung and liver.

Abstract

Corticosteroid-binding globulin (CBG) is the specific plasma transport glycoprotein for glu- cocorticoids. Circulating CBG is mainly synthesized in liver but, its synthesis has been located also in other organs as placenta, kidney and adipose tissue with unknown role. Using an experimental model of acute pancreatitis in cbg -/- mice we investigated whether changes in CBG affect the progression of the disease as well as the metabolism of gluco- corticoids in the lung. Lack of CBG does not modify the progression of inflammation associ- ated to pancreatitis but resulted in the loss of gender differences in corticosterone serum levels. In the lung, CBG expression and protein level were detected, and it is noteworthy that these showed a sexual dimorphism opposite to the liver, i.e. with higher levels in males. Reduced expression of 11 β -HSD2, the enzyme involved in the deactivation of corticoste- rone, was also observed. Our results indicate that, in addition to glucocorticoids transporter, CBG is involved in the gender differences observed in corticosteroids circulating levels and plays a role in the local regulation of corticosteroids availability in organs like lung.