Vascular endothelial growth factor increases messenger RNAs encoding cyclooxygenase-II and membrane-associated prostaglandin E synthase in rat luteal cells.
Vascular endothelial growth factor (VEGF) is known to be necessary for the vascularization of the developing corpus luteum. Our recent data suggested that cyclooxygenase-II (COX-II) may play a role in the formation of vascular plexuses in developing corpora lutea of the rat. Here we examined the relationship between VEGF and the expression of prostaglandin (PG)- metabolizing enzymes in rat ovarian luteal cells. VEGF treatment caused a dose-dependent increase in the expression of COX-II and membrane-associated PGE synthase (mPGES) mRNA in cultured rat luteal cells. However, pretreatment of the luteal cells with a selective COX-II inhibitor, NS-398, abolished the VEGF-enhanced mPGES mRNA expression. VEGF also increased PGE2 secretion. Conversely, PGE2 dose-dependently stimulated VEGF mRNA expression. Furthermore, VEGF induced VEGF mRNA expression, but this effect was abolished by NS-398 pretreatment. These findings suggest that VEGF enhances PGE2 production by stimulating COX-II and mPGES expression in rat corpus luteum and that the effect of VEGF on luteal cells may be partially mediated by this stimulation of PGE2 production.
Sakurai
T
T
Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Horinouchi, 1432-1, Tokyo, 192-0392, Japan.
Tamura
K
K
Kogo
H
H
D000818:Animals; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism*; D051546:Cyclooxygenase 2; D005260:Female; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D013268:Stimulation, Chemical; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000494:pharmacology*
D007527:Isoenzymes; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C495729:membrane-associated PGE synthase, rat