This study examines the regulation of major enzymes in prostaglandin E(2) (PGE(2)) synthesis by glucocorticoids in separate cultures of human amnion epithelial and fibroblast cells at term. Cytosolic phospholipase A(2) (cPLA(2)), cytosolic PGES (cPGES), and microsomal PGES (mPGES) mRNA were expressed at similar levels in both cell types, whereas a greater prostaglandin H synthase type 2 (PGHS-2) mRNA expression was observed in amnion fibroblasts than in epithelial cells. Amnion fibroblasts produced 50-fold more PGE(2) per cell than epithelial cells. Dexamethasone (0.01-1 microM) increased PGE(2) production in amnion fibroblasts in a concentration-dependent manner but did not affect PGE(2) production in amnion epithelial cells. Both mRNA and protein expression of cPLA(2) and PGHS-2 but not cPGES and mPGES were increased in a dose-dependent manner by dexamethasone (0.01-1 microM) in amnion fibroblasts. Induction of cPLA(2) and PGHS-2 mRNA by dexamethasone was blocked by RU486. Dexamethasone did not affect PGHS-2, cPGES, and mPGES mRNA expression in amnion epithelial cells. In conclusion, amnion fibroblasts express a higher level of PGHS-2 mRNA and produced more PGE(2) per cell than amnion epithelial cells at term of human pregnancy. Glucocorticoids increase PGE(2) production only in the amnion fibroblasts mainly through induction of cPLA(2) and PGHS-2 expression.