The effect of the antiprogestins RU 486 and ZK 98734 on the synthesis and metabolism of prostaglandins F2 alpha and E2 in separated cells from early human decidua.
Enriched preparations of glandular and stromal cells were obtained from early human decidua and incubated for 24 h in the presence of two progesterone antagonists, RU 486 (17 beta-hydroxy-11 beta-[4-dimethylaminophenyl]17 alpha-[1-propynyl]-estra-4,9-dien-3-one) and ZK 98734 (17 beta-hydroxy-11 beta-4[4-dimethylaminophenyl]17 alpha-[3-hydroxy-1-propynyl]estra-4,9-dien-3-one) to determine the effect of the antiprogestins on the release of prostaglandin F2 alpha (PGF2 alpha) and PGE2 and their subsequent conversion to 15-keto-13,14-dihydro-PGF2 alpha and 15-keto-13,14-dihydro-PGE2. In the presence of exogenous arachidonic acid (AA, 30 microM), both steroids stimulated PGF2 alpha release by glandular, but not stromal, cells (P less than 0.001) and inhibited the metabolism of PGF2 alpha by the glandular fraction (P less than 0.005 and P less than 0.001 respectively). In the absence of exogenous AA, RU 486 and ZK 98734 stimulated the release of PGF2 alpha from glandular, but not stromal, cells (P less than 0.001 and P less than 0.005, respectively). Neither steroid altered the release or metabolism of PGE2 when the cells were incubated with AA, but both RU 486 and ZK 98734 increased the release of PGE2 by glandular, but not stromal, cells when incubated without AA (P less than 0.005 and P less than 0.001, respectively). Both steroids inhibited the metabolism of PGE2 under these conditions (P less than 0.05). These results suggest that 1) antiprogestins stimulate the synthesis of PGs by glandular cells in early human decidua, but do not alter the synthesis of PGs by stromal cells; 2) this stimulation of PG synthesis involves an effect on cyclooxygenase activity and is not a consequence of increased availability of endogenous AA; 3) the metabolism of PGs by glandular cells is altered by RU 486 and ZK 98734; 4) as RU 486 has greater antiglucocorticoid activity than ZK 98734, these results suggest that both steroids act on decidua by antagonizing endogenous progesterone rather than glucocorticoid activity.
D002478:Cells, Cultured; D003656:Decidua / Q000378:metabolism*; D015237:Dinoprost; D015232:Dinoprostone; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015735:Mifepristone; D011247:Pregnancy; D011372:Progestins / Q000037:antagonists & inhibitors*; D011458:Prostaglandins E / Q000096:biosynthesis / Q000378:metabolism*; D011460:Prostaglandins F / Q000096:biosynthesis / Q000378:metabolism*
D004963:Estrenes; D011372:Progestins; D011458:Prostaglandins E; D011460:Prostaglandins F; D015735:Mifepristone; C048260:lilopristone; D015237:Dinoprost; D015232:Dinoprostone