Glucocorticoids increase the responsiveness of cells in culture to prostaglandin E 1

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Abstract
The influence of steroid hormones on the response of human astrocytoma cells (1321N1) to prostaglandin E1 (PGE1) was investigated. Responsiveness to PGE1 was determined by measuring the conversion of [3H]ATP to cyclic [3H]AMP in cells prelabeled with [3H]adenine. After incubation of the cells with dexamethasone, a marked increase in both the maximal effect (2- to 3-fold) and the potency (5-fold) to PGE1 was observed. The effect was specific for the action of PGE1 in that no change in the response of the cells to isoproterenol was observed. The EC50 [median effective concentration] for dexamethasone was 0.001 .mu.M and the effect was dependent on the presence of serum. The effect of dexamethasone was first observed after a 30-60 min lag and was maximal by 6-8 h. Preconfluent cultures (3 days after seeding) exhibited optimal responsiveness to glucocorticoids. Both hydrocortisone and corticosterone mimicked the effect of dexamethasone but both were less potent. The action of dexamethasone was blocked by progesterone, testosterone and 17 .alpha.-methyltestosterone. Cycloheximide, at a concentration (1.0 .mu.g/ml) that blocked protein synthesis (> 90%) in 1321N1 cells, totally prevented the effect of dexamethasone on the response of the cells to PGE1. Upon removal of dexamethasone from cells treated for 16 h, responsiveness to PGE1 returned to control levels with a half-time of 4 h. Dexamethasone also was found to increase the response to PGE1 of a Rous sarcoma virus-transformed human astrocytoma cell line and the WI-38 human fibroblast line. The most obvious interpretation of the findings is that glucocorticoids induce the synthesis of a protein that selectively modifies the sensitivity of adenylate cyclase to PGE1.