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

摘要

This study was undertaken to investigate how prostaglandin F2a (PGF2a) increases PGF2a synthesis and PTGS2 expression in the corpusluteum of pseudopregnant rats. We further investigated the molecular mechanism by which PGF2a stimulates PTGS2 expression. PGF2a(3 mg/kg) or phosphate buffer as a control was injected s.c. on day 7 of pseudopregnancy. Ptgs2 mRNA expression and PGF2aconcentrations in the corpus luteum were measured at 2, 6, and 24 h after PGF2a injection. PGF2a significantly increased Ptgs2 mRNAexpression at 2 h and luteal PGF2a concentrations at 24 h. PGF2a significantly decreased serum progesterone levels at all of the timesstudied. Simultaneous administration of a selective PTGS2 inhibitor (NS-398, 10 mg/kg) completely abolished the increase in lutealPGF2a concentrations induced by PGF2a. PGF2a increased NFKB p65 protein expression in the nucleus of luteal cells 30 min after PGF2ainjection, and electrophoretic mobility shift assay revealed that PGF2a increased binding activities of NFKB to the NFKB consensussequence of the Ptgs2 gene promoter. Simultaneous administration of both superoxide dismutase and catalase to scavenge reactiveoxygen species (ROS) inhibited the increases of nuclear NFKB p65 protein expression, lipid peroxide levels, and Ptgs2 mRNA expressioninduced by PGF2a. In conclusion, PGF2a stimulates Ptgs2 mRNA expression and PGF2a synthesis through NFKB activation via ROS in thecorpus luteum of pseudopregnant rats.