Glucocorticoid regulation of amidating enzyme in a neoplastic C-cell line.
Posttranslational carboxyl-terminal amidation of many peptides is accomplished by peptidylglycine alpha-amidating monooxygenase. We have previously demonstrated that glucocorticoids stimulate production of amidated products by the CA-77 rat medullary thyroid carcinoma cell line. The present investigation was undertaken to determine whether amidation enzyme activity changes in parallel. Enzyme activity, similar to that found in other tissues, was readily detected in cell extracts and conditioned cultured medium. Stimulation with the calcitonin secretagogue calcium increased secretion of enzyme activity and lowered cell extract activity. Treatment of cultures with dexamethasone, but no other steroid, decreased by 50-70% the basal amidation enzyme activity secreted. There was no associated change in cellular activity. The decrease in medium activity was partially reversible and steroid-dose dependent. The glucocorticoid-induced change in medium activity was due to a decreased Vm. These experiments demonstrate that the alpha-amidating activity of the CA-77 cells can be hormonally regulated.
Birnbaum
R S
RS
Research Service and Geriatric Research, Veterans Administration Medical Center, Tacoma, WA 98493.
Bertelsen
A H
AH
Roos
B A
BA
D000818:Animals; D003470:Culture Media; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D006899:Mixed Function Oxygenases; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000201:enzymology*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000032:analysis*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003470:Culture Media; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D003907:Dexamethasone; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; D000587:Oxidoreductases Acting on CH-NH Group Donors