Waclawik Agnieszka, Jabbour Henry N, Blitek Agnieszka, Ziecik Adam J
Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-747 Olsztyn, Poland.
Endocrinology. 2009 Aug;150(8):3823-32. doi: 10.1210/en.2008-1499. Epub 2009 Apr 9.
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.
在着床前，猪子宫内膜和滋养层会合成大量具有黄体保护作用的前列腺素雌二醇-17β（E₂）（PGE₂）。我们推测胚胎信号、E₂和PGE₂会调节PG合成关键酶的表达：PG内过氧化物合酶-2（PTGS2）、微粒体PGE合酶（mPGES-1）、PGF合酶（PGFS）和PG 9-酮还原酶（CBR1），以及子宫内膜内PGE₂受体（PTGER2和-4）的表达和信号传导。我们确定了发情周期和妊娠期PGE₂在子宫内膜中的作用位点。从发情周期第11 - 12天的后备母猪（n = 6）获取子宫内膜组织外植体，用赋形剂（对照）、PGE₂（100 nM）、E₂（1 - 100 nM）或佛波醇12-肉豆蔻酸酯13-乙酸酯（100 nM，阳性对照）进行处理。E₂通过提高子宫内膜外植体中mPGES-1 mRNA以及PTGS2和mPGES-1蛋白的表达来增加PGE₂分泌。相比之下，E₂降低了PGFS和CBR1蛋白的表达。E₂还刺激了PTGER2蛋白含量，但对PTGER4蛋白含量无影响。PGE₂增强了mPGES-1和PTGER2 mRNA以及PTGS2、mPGES-1和PTGER2蛋白的表达。PGE₂对PGFS、CBR1和PTGER4的表达以及PGF₂α释放没有影响。用PGE₂处理子宫内膜组织会增加cAMP的产生。与PTGER2拮抗剂（AH6809）共同处理可显著抑制PGE₂介导的cAMP产生，但与PTGER4拮抗剂（GW 627368X）共同处理则无此作用。PTGER2蛋白定位于子宫内膜的腔上皮、腺上皮和血管中，在妊娠第11 - 12天显著上调。我们的结果表明，E₂通过对PG合成进行酶促修饰来防止黄体溶解，并且E₂、PGE₂和子宫内膜PTGER2参与了猪子宫内膜中的PGE₂正反馈回路。
