Induction of the acute-phase reactant, alpha 1-acid glycoprotein, by glucocorticoids in rat hepatoma cells.
alpha 1-acid glycoprotein (alpha 1-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 (alpha 1-AGP) and Mr greater than 180,000, both of which are greatly enhanced by glucocorticoid treatment. The amount of alpha 1-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 1/2 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 alpha 1-AGP mRNA induction. This is a secondary hormonal response since inhibition of protein synthesis blocks the induction of alpha 1-AGP mRNA by dexamethasone whereas the induction of mouse mammary tumor virus (MMTV) RNA is unaffected.
D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental; D009961:Orosomucoid / Q000096:biosynthesis*; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014444:Tyrosine Transaminase / Q000096:biosynthesis; D014775:Virus Activation / Q000187:drug effects
D005938:Glucocorticoids; D009961:Orosomucoid; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D011374:Progesterone; D003907:Dexamethasone; D003513:Cycloheximide; D014444:Tyrosine Transaminase