Prostaglandin F2α (PGF2α) stimulates PTGS2 expression and PGF2α synthesis through NFKB activation via reactive oxygen species in the corpus luteum of pseudopregnant rats

Abstract This study was undertaken to investigate how prostaglandin F 2α (PGF 2α ) increases PGF 2α synthesis and PTGS2 expression in the corpus luteum of pseudopregnant rats. We further investigated the molecular mechanism by which PGF 2α stimulates PTGS2 expression. PGF 2α (3 mg/kg) or phosphate buffer as a control was injected s.c. on day 7 of pseudopregnancy. Ptgs2 mRNA expression and PGF 2α concentrations in the corpus luteum were measured at 2, 6, and 24 h after PGF 2α injection. PGF 2α significantly increased Ptgs2 mRNA expression at 2 h and luteal PGF 2α concentrations at 24 h. PGF 2α significantly decreased serum progesterone levels at all of the times studied. Simultaneous administration of a selective PTGS2 inhibitor (NS-398, 10 mg/kg) completely abolished the increase in luteal PGF 2α concentrations induced by PGF 2α . PGF 2α increased NFKB p65 protein expression in the nucleus of luteal cells 30 min after PGF 2α injection, and electrophoretic mobility shift assay revealed that PGF 2α increased binding activities of NFKB to the NFKB consensus sequence of the Ptgs2 gene promoter. Simultaneous administration of both superoxide dismutase and catalase to scavenge reactive oxygen species (ROS) inhibited the increases of nuclear NFKB p65 protein expression, lipid peroxide levels, and Ptgs2 mRNA expression induced by PGF 2α . In conclusion, PGF 2α stimulates Ptgs2 mRNA expression and PGF 2α synthesis through NFKB activation via ROS in the corpus luteum of pseudopregnant rats.