The effect of dexamethasone on parathyroid hormone stimulation of adenylate cyclase in ROS 17/2.8 cells.
Treatment of ROS 17/2.8 osteosarcoma-derived cells with dexamethasone potentiates the PTH stimulation of adenylate cyclase in these cells, yielding a detectable response to as little as 10 pM PTH. Isoproterenol stimulation was also enhanced. The dexamethasone effect is first apparent at 12 h and increases with time of treatment. The apparent EC50 for dexamethasone is 3 nM. Hydrocortisone and corticosterone act similarly to dexamethasone, but require 30-fold higher concentrations. Dexamethasone treatment produces no change in high affinity phosphodiesterase activity. Glucocorticoid-potentiating effects are much more pronounced in whole cells than in broken cells and do not influence forskolin stimulation. Particulate fractions of dexamethasone-treated cells have higher adenylate cyclase specific activity, but are stimulated by guanyl-5'-yl imidodiphosphate to the same extent as control cells. These findings suggest that the glucocorticoids potentiate hormone responsiveness through promotion of hormone receptor-adenylate cyclase coupling by a mechanism dependent on cellular integrity.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005576:Colforsin; D003345:Corticosterone / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D012516:Osteosarcoma / Q000201:enzymology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013997:Time Factors
D004224:Diterpenes; D010281:Parathyroid Hormone; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D003907:Dexamethasone; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D003345:Corticosterone; D006854:Hydrocortisone