Dexamethasone regulation of alpha 1-acid glycoprotein and other acute phase reactants in rat liver and hepatoma cells.

The regulation of al-acid glycoprotein (al-AGP) in rat hepatoma tissue culture (HTC) cells by dexamethasone was assessed by cell-free translation of mRNA and by RNA-DNA hybridization techniques using a cloned double-stranded cDNA probe. The effect of dexamethasone on the mRNA level of aI-AGP was compared with the induction of mammary tumor virus (MTV) mRNA in viral infected HTC cells. The dose-response, kinetics of mRNA accumulation, and sensitivity to the glucocorticoid antagonist 17P-carboximide derivative of dexamethasone are identical for both al-AGP and MTV mRNA. The appearance of al-AGP mRNA is, however, different from that of MTV mRNA in that it is dependent on de novo protein synthesis. Dexamethasone acts similarly on nontransformed hepatic cells since the synthetic glucocorticoid mediates the accumulation of al-AGP mRNA in liver in vivo and increases the synthesis of al-AGP in primary cultures of adult hepatocytes. Quantitation of aI-AGP mRNA levels in HTC cells and liver after a 48-h treatment with dexamethasone yielded values of 3,800 and 10,000 copies of mRNA/cell, respectively. Since al-AGP represents a major acute phase reactant in rats, we determined whether dexamethasone influences the level of other mRNA species which are modulated by experimentally induced inflammation. Dexamethasone affects the expression of a subset of acute phase reactants; however, most of these steroid-mediated alterations, including increased al-AGP mRNA levels, occur in inflammation-induced adrenalectomized rats. The combined results from the experiments with HTC cells and livers suggest that aI-AGP and some other acute phase reactants are controlled by two effector systems, glucocorticoids and yet to be determined stress-related factor(s). Since al-AGP and other acute phase reactants can be induced in the apparent absence of glucocorticoids, it is not clear at this time whether endogenous glucocorticoids play a major role in regulating the mRNA concentrations of acute phase reactants.