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

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Abstract
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 Mr = 35,000–48,000 (α1-AGP) and Mr > 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 t½ 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.