Activity, synthesis, storage, and messenger RNA of cyclooxygenase in intrauterine tissues of guinea pigs near term and during labor

Abstract

Whether the reported gestation-dependent increase in cyclooxygenase activity in gestational tissues is due to an accumulation of cyclooxygenase in vivo or an increasing capacity to synthesize cyclooxygenase in vitro is unknown. In this study in guinea pigs, COX activity was estimated from the net production rates of prostaglandins E₂ and F_2α in the presence of optimal substrate concentrations. Cyclooxygenase activity in amnion increased between 45 days of gestation and labor in microsomes (150-fold in relation to PGF_2α production and 116-fold in relation to PGE₂ production) and in tissue explants (42-fold in relation to PGF_2α production). The capacity for de novo synthesis of cyclooxygenase after aspirin treatment increased nine-fold between 45 days of gestation and labor in amnion explants. Comparison of COX activity in amnion explants with or without prior aspirin treatment showed that COX activity is at least three-fold higher in controls than would be expected if the activity was due to de novo synthesis alone. Cyclooxygenase-2 mRNA predominated in amnion but neither cyclooxygenase-2 nor cyclooxygenase-1 mRNA levels (semi-quantitative RT-PCR) changed significantly. This suggests that the gestation-dependent increase in cyclooxygenase activity in guinea pig amnion is due in part to accumulation of cyclooxygenase in vivo, that COX-2 predominates, and that COX activity is not correlated with levels of COX mRNA.