Regulation of the production of placental protein 5 by human endometrial stromal cells; the role of prostaglandins E 2 and F 2α

Cultured human endometrial stromal cells were found to release placental protein 5 (PP5), a glycoprotein with properties of a serine protease inhibitor. Progesterone had no effect on PP5 release, but cholera toxin and 12- O -tetradecanoylphorbol 13-acetate stimulated PP5 release in a time- and concentration-dependent fashion. Prostaglandin E 2 (PGE 2 ) caused a parallel increase in cAMP and PP5 release in a time-and concentration-dependent fashion. The lowest PGE 2 concentration which increased cAMP and PP5 release was 1 × 10 -9 M. Maximal increase in cAMP (42-fold) and PP5 (25-fold) release was obtained by 10 -5 M PGE 2. Stimulation of cAMP by PGE 2 was detectable at 15 min and was followed by an increased PP5 release at 24 h. The concentrations of prostaglandin F 2α (PGF 2α ) which stimulated cAMP and PP5 release were pharmacological suggesting that this effect is nonspecific. The results indicate that the activation of cAMP- and protein kinase C-dependent pathways in endometrial stromal cells increases the production of PP5. PGE 2 could be one of the physiological ligands employing the cAMP-dependent pathway in endometrial stromal cells.