The Stimulation of Prostaglandin Production by Two Antiprogesterone Steroids in Human Endometrial Cells

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Abstract
Endometrial stromal cells and isolated endometrial glands obtained from women during days 6–26 of the ovarian cycle were cultured for 24 h in the presence of the progesterone antagonists 17β-hydroxy-llβ-[4-dimethylaminophenyl] 17α-[l-propynyl.[estra-4,9-dien-3-one (RU486) and 17β- hydroxy-llβ-[4-dimethylaminophenyl]17α-[3-hydroxy-l-propenyl]-estra-4,9-dien-3-one (ZK 98734). Both steroids stimulated prostaglandin F2α (PGF2α) production by stromal cells in a dosedependent manner, in doses ranging from 10–1000 nM. Progesterone (100 nM) inhibited RU486 stimulation, except at the highest dose of antiprogestin. PGE2 was produced in smaller amounts than PGF2α, but, when measurable, it also increased in the presence of RU486. In contrast, RU486 did not increase PG production by endometrial glands. In an experiment to determine the effect of pretreatment, stromal cells were incubated for 24 h with 1000 nM progesterone or RU486 (all with 100 nM 17β-estradiol) with either 30 or 6 μM arachidonic acid. These six batches of cells were incubated for a second 24 h with either progesterone or antiprogestin. Cells pretreated with the higher dose of arachidonic acid had a marked increase in PGF2± production during the second 24 h only when also pretreated with progesterone. This finding suggests that progesterone allows an accumulation of PG precursor in a suitable accessible pool. Pretreatment with progesterone also allowed a greater conversion of PG to its 13,14-dihydro-15-keto metabolite. These results suggest that antiprogesterone steroids may act as menstrual regulators by: 1) stimulating endogenous PG production within the endometrial stromal cells and 2) inhibiting PG catabolism. (J Clic Endocrinol Metab62: 1116, 1986)