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The Effect of the Antiprogestins RU 486 and ZK 98734 on the Synthesis and Metabolism of Prostaglandins F₂ and E₂ in Separated Cells from Early Human Decidua

Medical Research Council, Reproductive Biology Unit, Centre for Reproductive Biology Edinburgh, EH3 9EW Scotland

Address requests for reprints to: Dr. S. K. Smith, Medical Research Council, Reproductive Biology Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh, EH3 9EW Scotland.

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 (17β-hydroxy-11β-[4-dimethylaminophenyl] 17-[1-propynyl] estra-4,9-dien-3-one) and ZK 98734 (17β-hydroxy-llβ-[4-di-methylaminophenyl]17-[3-hydroxy-l-propynyl]estra-4,9-dien-3-one) to determine the effect of the antiprogestins on the release of prostaglandin F₂ (PGF₂) and PGE₂ and their subsequent conversion to 15-keto-13,14-dihydro-PGF₂ and 15-keto-13,14-dihydro-PGE₂. In the presence of exogenous arachidonic acid (AA, 30 µM), both steroids stimulated PGF₂ release by glandular, but not stromal, cells (P < 0.001) and inhibited the metabolism of PGF₂ by the glandular fraction (P < 0.005 and P < 0.001 respectively). In the absence of exogenous AA, RU 486 and ZK 98734 stimulated the release of PGF₂ from glandular, but not stromal, cells (P < 0.001 and P < 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 < 0.005 and P < 0.001, respectively). Both steroids inhibited the metabolism of PGE₂ under these conditions (P < 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.

Received January 14, 1987.

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