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

Abstract

AbstractThis study was undertaken to investigate how prostaglandin F2α(PGF2α) increases PGF2αsynthesis and PTGS2 expression in the corpus luteum of pseudopregnant rats. We further investigated the molecular mechanism by which PGF2αstimulates PTGS2 expression. PGF2α(3 mg/kg) or phosphate buffer as a control was injected s.c. on day 7 of pseudopregnancy.Ptgs2mRNA expression and PGF2αconcentrations in the corpus luteum were measured at 2, 6, and 24 h after PGF2αinjection. PGF2αsignificantly increasedPtgs2mRNA expression at 2 h and luteal PGF2αconcentrations at 24 h. PGF2αsignificantly 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 PGF2αconcentrations induced by PGF2α. PGF2αincreased NFKB p65 protein expression in the nucleus of luteal cells 30 min after PGF2αinjection, and electrophoretic mobility shift assay revealed that PGF2αincreased binding activities of NFKB to the NFKB consensus sequence of thePtgs2gene 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, andPtgs2mRNA expression induced by PGF2α. In conclusion, PGF2αstimulatesPtgs2mRNA expression and PGF2αsynthesis through NFKB activation via ROS in the corpus luteum of pseudopregnant rats.