Progesterone and antiprogestins, a comparison of their effect on prostaglandin production by human secretory phase endometrium and decidua

The mechanism by which progesterone inhibits PG production is not clear. In systems using isolated human endometrial fragments, progesterone has been shown to inhibit PG production markedly. We have used such a system to test the action of two antiprogesterone steroids RU486 (Roussell-Uclaf) and ZK98734 (Schering) on isolated human endometrial and decidual tissue, with and without added progesterone. Progesterone (200nM) reduced PGF_2α production by the secretory phase endometrium from 10.9ng/mg tissue/24 hr to1.9 ng/mg/24hr on the third day of culture (p<01) and this effect was antagonised by the addition of either 200nM RU486 or 200nM ZK98734 (6.3 and 7.2 ng/mg /24 hr respectively). The antiprogestins on their own showed a slight inhibitory effect on day 3 and RU486 treatment resulted in a significant (p<.05) decrease in PG production from control. PGE and the main 13,14-dihydro-15-keto metabolites of E and F were also significantly decreased by progesterone and restored by the aMiprogestins. The PG production by decidua increased on days 2 and 3 in response to progesterone + antiprogestins but this was not significant. This data shows that the inhibition of PG production shown by progesterone, acting on secretory phase endometrium cultured as tissue fragments, is reversible by the receptor blocking antiprogestins.