Prostaglandin F2-alpha Stimulates Cyclooxygenase-2 Expression and Prostaglandin F2-alpha Synthesis Through NF-kappaB Activation via Reactive Oxygen Species in the Corpus Luteum of Pseudopregnant Rats.

Abstract

This study was undertaken to investigate how prostaglandin F2α (PGF2α) increases PGF2α synthesis and cyclooxygenase-2 (COX-2) expression in the corpus luteum in pseudopregnant rats. We further investigated the molecular mechanism by which PGF2α stimulates COX-2 expression. PGF2α (3 mg/kg) or phosphate buffer as a control was 5 injected subcutaneously on day 7 of pseudopregnancy. COX-2 mRNA expression and PGF2α concentrations in the corpus luteum were measured 2 h, 6 h, and 24 h after PGF2α injection. PGF2α significantly increased COX-2 mRNA expression at 2 h and luteal PGF2α concentrations at 24 h. PGF2α significantly decreased serum progesterone levels at all of the times studied. Simultaneous administration of a selective COX-2 inhibitor 10 (NS-398, 10 mg/kg) completely abolished the increase in luteal PGF2α concentrations induced by PGF2α. PGF2α increased NF-κB p65 protein expression in the nucleus of luteal cells 30 min after PGF2α injection, and electrophoretic mobility shift assay revealed that PGF2α increased binding activities of NF-κB to the NF-κB consensus sequence of the COX-2 gene promoter. Simultaneous administration of both superoxide dismutase (SOD) 15 Page 2 of 39