Estradiol-17β, prostaglandin E2 (PGE2), and the PGE2 receptor are involved in PGE2 positive feedback loop in the porcine endometrium

Abstract

Before implantation, the porcine endometrium and trophoblast synthesize elevated amounts of luteoprotective prostaglandin estradiol-17β(E 2) (PGE2). We hypothesized that embryo signal, E 2, and PGE2 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 PGE2 receptor (PTGER2 and -4) expression and signaling within the endometrium. We determined the site of action of PGE2 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), PGE2 (100 nM), E2 (1-100 nM), or phorbol 12-myristate 13-acetate (100 nM, positive control). E2 increased PGE2 secretion through elevating expression of mPGES-1 mRNA and PTGS2 and mPGES-1 protein in endometrial explants. By contrast, E2 decreased PGFS and CBR1 protein expression. E2 also stimulated PTGER2 but not PTGER4 protein content. PGE2 enhanced mPGES-1 and PTGER2 mRNA as well as PTGS2, mPGES-1, and PTGER2 protein expression. PGE2 had no effect on PGFS, CBR1, and PTGER4 expression and PGF2α release. Treatment of endometrial tissue with PGE2 increased cAMP production. Cotreatment with PTGER2 antagonist (AH6809) but not PTGER4 antagonist (GW 627368X) inhibited significantly PGE2-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 E2 prevents luteolysis through enzymatic modification of PG synthesis and that E2, PGE2, and endometrial PTGER2 are involved in a PGE2 positive feedback loop in porcine endometrium. Copyright © 2009 by The Endocrine Society.