Prostaglandins (PGs) interact with specific receptors on plasma membranes to regulate myometrial activity in many species. The present study examined whether the expression of relaxant prostaglandin E receptor subtype two (EP(2)) and contractile prostaglandin F receptor (FP) mRNA in the rat uterus is changed during various states of pregnancy and regulated by steroid hormones. Expression of mRNA for EP(2) and FP receptors in the full-thickness uteri was analyzed by reverse transcription-polymerase chain reaction using specific primers. Abundance of receptor mRNA was expressed relative to beta-actin mRNA. Results showed that 1) mRNA for EP(2) receptors in the rat uterus was substantially increased during pregnancy (320%) compared with the nonpregnant state (100%, P < 0.01), and declined during labor at term (36% vs. 100% in control, P < 0.01); 2) mRNA expression for FP receptors in rat uterus was increased during pregnancy (333% vs. 100% in nonpregnant rats, P < 0. 01) and reached maximal levels during labor (515% vs. 100% in control, P < 0.01); 3) upon RU-486 treatment on Day 19 of pregnancy, uterine EP(2) receptor mRNA levels were decreased (18% vs. 100% in control, P < 0.01), and FP mRNA levels were increased (357% vs. 100% in control, P < 0.01); 4) with ICI 164384 (an antiestrogen) treatment on Day 19 of gestation, uterine FP receptor mRNA levels were decreased without effects on EP(2) receptors; 5) in ovariectomized (ovx) rats, progesterone increased EP(2) (163% vs. 100% in control, P < 0.01) and had no effects on FP receptor mRNA expression in the rat uterus; 6) estradiol increased FP receptor mRNA levels (358% vs. 100% in control, P < 0.01) and had no effects on EP(2) mRNA in the ovx rat uterus. Therefore, we conclude that steroid hormones modulate the mRNA for relaxant EP(2) and contractile FP receptors for PGs in the uterus and thus regulate uterine activity during pregnancy and labor.