Glucocorticoid hormones increase the activity of gamma-glutamyltransferase in a highly differentiated hepatoma cell line.
Gamma-Glutamyltransferase activity was detected in the plasma membrane of the highly differentiated hepatoma cell line Fao, (0.93 mU/mg cell protein). Dexamethasone (1 microM) provoked a 2-3-fold increase in the activity of the enzyme in the presence of fetal calf serum. Maximal induction occurred 48-72 h after addition of the glucocorticoid to the cell culture medium. The hormonal specificity was demonstrated by the relative potencies of several glucocorticoids and sex steroids: hydrocortisone and corticosterone increased gamma-glutamyltransferase activity while tetrahydrocorticosterone and all sex steroids tested were ineffective. The effect of dexamethasone on gamma-glutamyltransferase activity wa specific since the activities of several other plasma membrane enzymes were not modified. The mechanism of the dexamethasone-induced increase in gamma-glutamyltransferase activity was neither by modification of the affinity of the enzyme for its substrates nor by alteration of the subcellular distribution of the enzyme. This increase was prevented by cycloheximide and actinomycin D. The data presented are consistent with a specific glucocorticoid receptor-mediated induction of gamma-glutamyltransferase activity in Fao cells. The kinetic parameters of the induction process by glucocorticoids are very similar to those found in adult rat liver. These results suggest that the Fao cell line is a very convenient system for the study of the molecular mechanisms of glucocorticoid effects on differentiated cells.
D000217:Acyltransferases / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase; D002454:Cell Differentiation; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003345:Corticosterone / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004790:Enzyme Induction; D006854:Hydrocortisone / Q000494:pharmacology; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D051381:Rats; D011503:Transglutaminases
D000305:Adrenal Cortex Hormones; D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide; D000217:Acyltransferases; D011503:Transglutaminases; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000262:Adenylyl Cyclases; D003345:Corticosterone; D006854:Hydrocortisone