Prostaglandin F2α (PGF2α) stimulates PTGS2 expression and PGF2α synthesis through NFKB activation via reactive oxygen species in the corpus luteum of pseudopregnant rats.
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.
Taniguchi
Ken
K
Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan.
Matsuoka
Aki
A
Kizuka
Fumie
F
Lee
Lifa
L
Tamura
Isao
I
Maekawa
Ryo
R
Asada
Hiromi
H
Taketani
Toshiaki
T
Tamura
Hiroshi
H
Sugino
Norihiro
N
D000818:Animals; D003338:Corpus Luteum / Q000187:drug effects* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D011555:Pseudopregnancy / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D009578:Nitrobenzenes; D017382:Reactive Oxygen Species; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D015237:Dinoprost; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat