Glucocorticoid and prostaglandin: lack of an inhibitory effect by dexamethasone on the synthesis of 6-ketoprostaglandin F_1α in rat lung

High doses of dexamethasone (1-12 mg/kg twice daily) were administered to pregnant rats for 2 days. The effect of dexamethasone on fetal and maternal lung prostaglandin metabolism was examined on day 21 of gestation. Dexamethasone treatment at all dosages significantly increased conversion of [¹⁴C]-arachidonic acid to 6-ketoprostaglandin F_α in both fetal and maternal lung homogenates. This finding is similar to our earlier finding using lower dosages of dexamethasone and suggests that dexamethasone enhances lung prostaglandin synthetase activity. Because dexamethasone is known to inhibit the activity of phospholipases, we also measured lung immunoreactive 6-ketoprostaglandin F_α. The results showed that dexamethasone treatment did not diminish lung 6-keto-prostaglandin F_1α level even at the highest dosage used (12 mg/kg). These results suggest that high dosages of dexamethasone, such as those used in the clinical treatment of septic shock, do not inhibit synthesis of lung prostaglandin.