Glucocorticoid-mediated induction of glucocortin: a rapid primary response common to major target tissues.
Glucocorticoids are known to rapidly induce four proteins in rat thymus cells in time to account for the earliest known metabolic hormone effects. We report here an additional protein, which we refer to as "glucocortin" (Mr = 17,000, pI = 4.7). It is of special interest since it is the only protein rapidly induced in all of the glucocorticoid target cells we have examined. We have characterized the kinetics of glucocortin mRNA induction in isolated thymus cells. Giant two-dimensional gel electrophoretic analysis of in vitro translation products reveals a 2-fold increase in the level of translatable mRNA within 15 min of dexamethasone addition, with maximal stimulation (approximately equal to 7-fold) by 45 min. Cycloheximide does not reduce the hormone-mediated increase in glucocortin mRNA, suggesting that the induction represents a primary response to glucocorticoids. This protein is induced by dexamethasone in a dose-dependent manner, with maximal induction at 10(-6) M and partial inductions at concentrations as low as 10(-10) M. It is strongly induced by cortisol at 10(-6) M, but it is not induced by estradiol or testosterone or by thyroid hormone, even at concentrations as high as 10(-6) M. Deoxycorticosterone has no effect at 10(-8) M but does generate a half-maximal effect at 10(-6) M, a finding consistent with its status as a partial glucocorticoid agonist. In summary, glucocortin appears to be a primary glucocorticoid-induced protein that represents the most rapid induction so far detected, and it appears to be the only one that may be common to all glucocorticoid target cells.
Colbert
R A
RA
Young
D A
DA
D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005938:Glucocorticoids / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism*
D005938:Glucocorticoids; D011506:Proteins; D012333:RNA, Messenger; C047380:glucocortin protein, mouse; D003900:Desoxycorticosterone; D003907:Dexamethasone; D003513:Cycloheximide