title: Dissociation of steroid binding to receptors and steroid induction of biological activity in a glucocorticoid-responsive cell.
abstract: Glucocorticoid responses in two independently derived lines of rat hepatoma tissue culture cells (HTC and FU5-5) were examined. FU5-5 cells exhibited induction of the enzyme tyrosine aminotransferase (TAT) at concentrations of dexamethasone that were approximately 7-fold lower than that required for HTC cells. FU5-5 cells also displayed substantial TAT induction with steroids that were partial agonists, or antagonists, in HTC cells. The increased sensitivity of FU5-5 cells was not, however, due to an increased affinity of FU5-5 cell receptors for dexamethasone, as determined from cell-free and whole cell binding experiments. The differential steroid sensitivity for TAT induction was observed with three other, structurally different glucocorticoids, thus apparently ruling out steroid metabolism in one of the cell lines as a cause. Also, induction of TAT in FU5-5 cells occurred at approximately 9-fold lower steroid concentrations than were required for the induction of glutamine synthetase (GS) in the same cells. Thus, the dose-response curves for TAT induction in HTC cells and for GS induction in FU5-5 cells are closely correlated with the saturation curve for whole cell steroid binding to receptor sites, while the dose-response curve for TAT induction in FU5-5 cells is shifted to lower steroid concentrations. This represents the first report of dissociation of two supposedly primary, glucocorticoid-induced functions and indicates that identical receptor-mediated processes cannot be utilized by FU5-5 cells for the induction of TAT and GS. The involvement of second messengers or different nuclear processes are possible explanations for the unusual behavior of FU5-5 cells during glucocorticoid induction of TAT.
mesh_terms: D000818:Animals; D002460:Cell Line; D003470:Culture Media; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D008297:Male; D011281:Pregnatrienes / Q000494:pharmacology; D051381:Rats; D011915:Rats, Inbred BUF; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D014444:Tyrosine Transaminase / Q000096:biosynthesis*
chemical_list: D003470:Culture Media; D005938:Glucocorticoids; D011281:Pregnatrienes; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; C029415:deacylcortivazol; D003907:Dexamethasone; D014444:Tyrosine Transaminase; D006854:Hydrocortisone