Open AccessGlucocorticoids increase the responsiveness of cells in culture to prostaglandin E 1
Author(s) -
Stephen J. Foster,
John P. Perkins
Publication year - 1977
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.74.11.4816
Subject(s) - cycloheximide , endocrinology , dexamethasone , medicine , prostaglandin , cell culture , glucocorticoid , prostaglandin e , incubation , steroid hormone , chemistry , hormone , biology , biochemistry , genetics
The influence of steroid hormones on the response of human astrocytoma cells (1321N1) to prostaglandin E1 (PGE1 ) has been investigated. Responsiveness to PGE1 was determined by measuring the conversion of [3 H]ATP to cyclic [3 H]AMP in cells prelabeled with [3 H]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) of 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 for dexamethasone was 0.001 μM and the effect was dependent on the presence of serum. The effect of dexamethasone was first observed after a 30- to 60-min lag and was maximal by 6-8 hr. 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 17α-methyltestosterone. Cycloheximide, at a concentration (1.0 μg/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 hr, responsiveness to PGE1 returned to control levels with a half-time of 4 hr. 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 our findings is that glucocorticoids induce the synthesis of a protein that selectively modifies the sensitivity of adenylate cyclase to PGE1 .