Glucocorticoids Potentiate the Prostaglandin E1-Mediated Cyclic AMP Formation by a Cultured Murine Neuroblastoma Clone

The effect of steroid hormones on the prostaglandin E1 (PGE1)-mediated cyclic AMP formation by murine neuroblastoma clone N1E-115 was studied. Dexamethasone at submicromolar concentrations and corticosterone at micromolar concentrations (steroids with glucocorticoid activity) were able to modify the PGE1-mediated response whereas testosterone, progesterone, and estradiol each at 10 microM had no effect. Glucocorticoids added to the culture medium of N1E-115 cells produced an increase in the maximal response to PGE1 only after long-term (greater than or equal to 4 h) incubation with the hormone. Inhibitors of protein and RNA synthesis blocked this effect of glucocorticoids. Basal activity of adenylate cyclase in treated cells was twofold higher than that in control cells, and this enzyme seemed to be the primary target for the hormone action, since the activity of 3':5'-cyclic AMP phosphodiesterase and the binding of [3H]PGE1 to its receptors were not altered by glucocorticoid treatment. Our results indicate that glucocorticoids modulate receptor-mediated responses in cells of neural origin through a mechanism that involves induction of protein synthesis.     

Glucocorticoids Modify Differentially Dopamine- and Prostaglandin E1-Mediated Cyclic AMP Formation by the Cultured Human Astrocytoma Clone D384

The effects of steroid hormones on the cyclic AMP responses to stimulation of human astrocytoma cells (D384) by dopamine, prostaglandin E1 (PGE1), and isoprenaline were investigated. Incubation of D384 cells with dexamethasone resulted in a potentiation of the PGE1 and isoprenaline responses and a marked attenuation of the dopamine response. The time courses of the effects of dexamethasone on dopamine and PGE1 responses were similar, requiring long-term (at least 18 h) incubation of cells with the steroid. Concentration-response curves of dexamethasone effects on dopamine and PGE1 responses yielded similar Ka apparent values, suggesting a common mechanism. Cycloheximide, a protein synthesis inhibitor, prevented the effects of dexamethasone. Only steroids with glucocorticoid activity reproduced the dexamethasone effects. Direct stimulation of Gs with 5-guanylylimidodiphosphate and adenylate cyclase with forskolin revealed no significant differences in their activities in dexamethasone-treated and untreated cells. Furthermore, a comparison of the dopamine and PGE1 concentration-response curves obtained from dexamethasone-treated and untreated cells suggested that the affinity of the receptors for their agonists remained unchanged. These results suggest that glucocorticoids may alter protein synthesis and thereby the number of receptors expressed by D384 cells.