Glucocorticoid and estrogen regulation of corticosteroid-binding globulin production by rat liver.

We have recently demonstrated that rat liver can synthesize and secrete corticosteroid-binding globulin (CBG). The present study extends these observations and examines the hormonal regulation of hepatic CBG production. Male rats were pretreated by adrenalectomy and/or glucocorticoid or estrogen administration and the rate of CBG production was measured in vitro. The production rates were assessed by the generation of specific corticosterone binding sites in both a liver-slice preparation and in an isolated perfused liver. The two techniques showed qualitatively similar results. Adrenalectomy enhanced and glucorticoid administration inhibited the rate of CBG production and secretion. Pretreatment of male rats with estradiol stimulated the rate of CBG production. The production rates were 20- to 40-fold higher in the perfused liver demonstrating its superiority over the liver-slice system. The livers from intact rats secreted CBG binding sites at a rate of approximately 18 pmol/g liver per hours, generating an estimated 20% of the total CBG content of a rat each day. The possible clinical implications of the therapeutic use of glucocorticoids that bind to CBG, yet inhibit CBG production, are discussed.