Estradiol-17beta, prostaglandin E2 (PGE2), and the PGE2 receptor are involved in PGE2 positive feedback loop in the porcine endometrium.
Before implantation, the porcine endometrium and trophoblast synthesize elevated amounts of luteoprotective prostaglandin estradiol-17beta (E(2)) (PGE(2)). We hypothesized that embryo signal, E(2), and PGE(2) modulate expression of key enzymes in PG synthesis: PG-endoperoxide synthase-2 (PTGS2), microsomal PGE synthase (mPGES-1), PGF synthase (PGFS), and PG 9-ketoreductase (CBR1) as well as PGE(2) receptor (PTGER2 and -4) expression and signaling within the endometrium. We determined the site of action of PGE(2) in endometrium during the estrous cycle and pregnancy. Endometrial tissue explants obtained from gilts (n = 6) on d 11-12 of the estrous cycle were treated with vehicle (control), PGE(2) (100 nM), E(2) (1-100 nm), or phorbol 12-myristate 13-acetate (100 nm, positive control). E(2) increased PGE(2) secretion through elevating expression of mPGES-1 mRNA and PTGS2 and mPGES-1 protein in endometrial explants. By contrast, E(2) decreased PGFS and CBR1 protein expression. E(2) also stimulated PTGER2 but not PTGER4 protein content. PGE(2) enhanced mPGES-1 and PTGER2 mRNA as well as PTGS2, mPGES-1, and PTGER2 protein expression. PGE(2) had no effect on PGFS, CBR1, and PTGER4 expression and PGF(2alpha) release. Treatment of endometrial tissue with PGE(2) increased cAMP production. Cotreatment with PTGER2 antagonist (AH6809) but not PTGER4 antagonist (GW 627368X) inhibited significantly PGE(2)-mediated cAMP production. PTGER2 protein was localized in luminal and glandular epithelium and blood vessels of endometrium and was significantly up-regulated on d 11-12 of pregnancy. Our results suggest that E(2) prevents luteolysis through enzymatic modification of PG synthesis and that E(2), PGE(2), and endometrial PTGER2 are involved in a PGE(2) positive feedback loop in porcine endometrium.
Waclawik
Agnieszka
A
Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-747 Olsztyn, Poland. waclawik@pan.olsztyn.pl
Jabbour
Henry N
HN
Blitek
Agnieszka
A
Ziecik
Adam J
AJ
D000818:Animals; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology*; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D030762:Estrous Cycle / Q000378:metabolism; D005260:Female; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D010120:Oxytocics / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D000071876:Prostaglandin-E Synthases; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D013552:Swine
D004967:Estrogens; D010120:Oxytocics; D018078:Receptors, Prostaglandin E; D004958:Estradiol; D015237:Dinoprost; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone