The role of reactive oxygen species as bioactive substances in the regulation of luteal function

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This study was undertaken to investigate how prostaglandin F2α(PGF2α) increases PGF2αsynthesis and cyclooxygenase-2 (COX-2) expression in the corpus luteum in pseudopregnant rats. We further investigated the molecular mechanism by which PGF2αstimulates COX-2 expression. PGF2α (3 mg/kg) or phosphate buffer as a control was injected subcutaneously on day 7 of pseudopregnancy. COX-2 mRNA expression and PGF2αconcentrations in the corpus luteum were measured 2 h, 6 h, and 24 h after PGF2αinjection. PGF2αsignificantly increased COX-2 mRNA 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 COX-2 inhibitor (NS-398, 10 mg/kg) completely abolished the increase in luteal PGF2αconcentrations induced by PGF2α. PGF2αincreased NF-κB p65 protein expression in the nucleus of luteal cells 30 min after PGF2αinjection, and electrophoretic mobility shift assay revealed that PGF2αincreased binding activities of NF-κB to the NF-κB consensus sequence of the COX-2 gene promoter. Simultaneous administration of both superoxide dismutase (SOD) and catalase to scavenge reactive oxygen species (ROS) inhibited the increases of nuclear NF-κB p65 protein expression, lipid peroxide levels, and COX-2 mRNA expression induced by PGF2α. In conclusion, PGF2αstimulates COX-2 mRNA expression and PGF2αsynthesis through NF-κB activation via ROS in the corpus luteum of pseudopregnant rats.