Glucocorticoid-mediated inhibition of ornithine decarboxylyase activity in S49 lymphoma cells.
Incubation of wild-type S49 lymphoma cells with glucocorticoids, such as dexamethasone and hydrocortisone, inhibits the activity of ornithine decarboxylase (L-ornithine carboxylyase, EC 4.1.1.17), the rate-limiting enzyme in the pathway of polyamine biosynthesis. The kinetics of this inhibition are more rapid than the glucocorticoid-mediated growth arrest in the G1 phase of the cell cycle or in glucocorticoid-mediated cytolysis of these cells. The inhibition of ornithine decarboxylase activity by corticosteroids is specific for steroids of the glucocorticoid class. Results obtained with variant S49 cells having lesions in the pathways of glucocorticoid or cyclic AMP action indicate that cytoplasmic glucocorticoid receptors, as well as nuclear transfer of steroid--receptor complexes, are required for the inhibition of ornithine decarboxylase activity but that this inhibition does not require hormonal activation of adenylate cyclase or cyclic AMP-dependent protein kinase. Because glucocorticoid-mediated inhibition of ornithine decarboxylase occurs when cellular protein synthesis has decreased less than 20%, this inhibition may represent a specific glucocorticoid-mediated deinduction of ornithine decarboxylase in S49 cells. Inhibition of ornithine decarboxylase activity may offer a useful marker for suppression of growth and cell cycle progression in these and other lymphoma cells.
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology
D011965:Receptors, Glucocorticoid; D013256:Steroids; D003907:Dexamethasone; D000242:Cyclic AMP; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase