The effect of dexamethasone on parathyroid hormone stimulation of adenylate cyclase in ROS 17/2.8 cells

Abstract

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.