Inhibition of aromatase activity by 8-bromo-cyclic adenosine monophosphate in cultured first-trimester human trophoblast.

We have previously shown that 8-bromo-adenosine-3':5'-cyclic monophosphate inhibits production of estradiol from androgen precursors in trophoblast isolated from term placentas. In these experiments we sought to evaluate the effect of 8-bromo-adenosine-3':5'-cyclic monophosphate on aromatase activity in first-trimester trophoblast culture. Trophoblast cells were enzyme dispersed from first-trimester placentas and purified on a Percoll gradient. On the third and fourth day after dispersion cultures were treated with androstenedione or testosterone with and without 2 mmol/L 8-bromo-adenosine-3':5'-cyclic monophosphate. The quantity of estradiol, estrone, progesterone, human placental lactogen, and human chorionic gonadotropin was determined by radioimmunoassay. We concluded that in first-trimester trophoblast, as previously reported in term trophoblast, 8-bromo-adenosine-3':5'-cyclic monophosphate inhibited the production of estradiol from the supplied androgen precursors. Human chorionic gonadotropin and human placental lactogen production was stimulated by 8-bromo-adenosine-3':5'-cyclic monophosphate. Progesterone production was either stimulated or was unchanged by the presence of 8-bromo-adenosine-3':5'-cyclic monophosphate.