Induction of the Acute-Phase Reactant,α1-Acid Glycoprotein,by Glucocorticoids in Rat Hepatoma Cells

α1-acid glycoprotein (α₁-AGP), or orosomucoid, is shown to be inducible by glucocorticoids in HTC rat hepatoma cells. Immunoprecipitation of [³⁵S]methionine pulse-labeled proteins from these cells reveals secreted proteins of M_r = 35,000–48,000 (α₁-AGP) and M_r > 180,000, both of which are greatly enhanced by glucocorticoid treatment. The amount of α₁-AGP-specific mRNA in HTC cells is greatly increased (at least 100-fold) in response to glucocorticoids. The new steady-state level of RNA is approached with a t _½ of about 8 hr and the RNA consists of a single species of approximately 850 bases. The response is specific for glucocorticoids since: (i) the EC₅₀ for dexamethasone is 30 nM; (ii) the glucocorticoid antagonist, progesterone, inhibits the induction by dexamethasone; and (iii) a glucocorticoid receptor-deficient cell line is incapable of α₁-AGP mRNA induction. This is a secondary hormonal response since inhibition of protein synthesis blocks the induction of α₁-AGP mRNA by dexamethasone whereas the induction of mouse mammary tumor virus (MMTV) RNA is unaffected.