Progesterone treatment in vitro enhances prostaglandin E and forskolin-promoted cyclic AMP production in human endometrial stromal cells

Confluent human endometrial stromal cell cultures were exposed to steroids for up to 72 h and then stimulated with agonists of adenylate cyclase for 60 min. Neither steroid alone or in combination had significant effect on cyclic AMP production. However, when stromal cell adenylate cyclase was stimulated with a receptor-dependent agonist (prostaglandin E), or with forskolin (which acts at a post-receptor site), progesterone in oestradiol-primed cells markedly enhanced (P less than 0.05) the effect of both agonists. The presence of phenol red, a weak oestrogenic compound, in the standard culture medium was sufficient to allow the progesterone effect to be manifest. Moreover, while oestradiol alone had no significant effect on prostaglandin E or forskolin-stimulated cyclic AMP production, the simultaneous exposure of cells to oestradiol and progesterone was the most effective treatment. Short-term incubation (up to 120 min) with progesterone had no effect on agonist-induced cyclic AMP accumulation, indicating that progesterone elicits its effect by the classic nuclear mechanism of action. It is suggested that the potentiation by progesterone of prostaglandin E-promoted production of cyclic AMP represents an important aspect of the functional role progesterone plays in the preparation of the endometrium for implantation.