Steroid modulation of pregnenolone to progesterone conversion by human placental cells in vitro

Studies were performed to examine the production of progesterone by human placental cells in vitro. Samples of placentas from 22 women at term after spontaneous onset of labor and vaginal delivery were utilized. The tissue was dispersed into isolated cells with the use of collagenase, and suspensions of these cells were incubated with pregnenolone as substrate in the presence or absence of other compounds which may regulate progesterone production. These cell preparations produced progesterone in a dose-related fashion with exogenous pregnendone. The conversion of pregnenolone to progesterone occurred rapidly, with most of the conversion completed during the first hour of incubation. The conversion was inhibited by dehydroepiandrosterone, estrone, androstenedione, and testosterone (p < 0.001 in all cases). The inhibitory effect of androstenedione and testosterone was not dependent on aromatization to estrogen. Dihydrotestosterone and 5α-pregnanedione resulted in a significant increase in the amount of progesterone present (p < 0.001). In preliminary experiments, gonadotropin-releasing hormone, salbutamol, and propranolol were without significant effect in this system. We conclude that this system is a useful model for studying progesterone production by human placental tissue, and that placental progesterone production may be significantly influenced by the presence of other steroid hormones.