The roles of Ca2+ and adenosine 3',5'-monophosphate in the regulation of progesterone production by human placental tissue.

The effects of Ca2+ and cAMP on progesterone production by placental tissue were studied. Term placentas obtained from normal pregnant women were perfused with sterile saline to remove blood, and the minced trophoblastic tissue was incubated in vitro. The rate of progesterone secretion by the trophoblastic tissue was 47.5 +/- 5.0 (+/- SE) ng/mg cell protein X h (control) at 450 micrograms low density lipoprotein/mL. The rates of progesterone production and cAMP accumulation were accelerated 3.0- and 1.7-fold, respectively, by 10(-5) M terbutaline, and the terbutaline effect was blocked by the addition of 50 microM N-(6-aminohexyl)5-chloro-1-naphthalenesulfonamide (W-7) or 50 microM trifluoperazine. Whereas progesterone secretion by placental explants cultured in medium containing low density lipoprotein with 1 microM A23187 (calcium ionophore) reached a rate of 128.5 +/- 8.5 ng/mg cell protein X h, incubation of placental explants with A23187 caused a highly significant, dose-related decrease in terbutaline-stimulated cAMP accumulation in the presence of 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor. Inhibition by A23187 was Ca2+ dependent, since incubation in a Ca2+-free medium with EGTA blocked its effect. Intracellular Ca2+ is apparently necessary for placental progesterone production; enhancement of progesterone production by beta2-stimulation is mediated by intracellular Ca2+ and cAMP.