Effects of adenosine 3',5'-cyclic monophosphate, forskolin, and cholera toxin on hormone production in human term placental cells.

Trophoblast cells from human term placenta in monolayer culture were used to investigate the role of adenosine 3',5'-cyclic monophosphate in the production of human chorionic gonadotropin and estradiol-17 beta. The intracellular concentration of adenosine 3',5'-cyclic monophosphate was elevated by (1) addition of an adenosine 3',5'-cyclic monophosphate analogue, 8-bromoadenosine 3',5'-cyclic monophosphate, (2) inhibition of the hydrolysis of Gs-GTP complex by cholera toxin, and (3) direct stimulation of adenylate cyclase with forskolin. Addition of 2 mmol/L of 8-bromoadenosine 3',5'-cyclic monophosphate markedly increased the accumulation of human chorionic gonadotropin in the culture medium on days 2, 3, and 4 of treatment. Likewise, addition of cholera toxin (0.2 microgram/ml) or forskolin (50 mumol/L) also enhanced human chorionic gonadotropin production. On the other hand, the production of estradiol-17 beta was significantly inhibited by 8-bromoadenosine 3',5'-cyclic monophosphate, at the same time that human chorionic gonadotropin production was enhanced in the same experiments. These results further support a differential role of adenosine 3',5'-cyclic monophosphate on human chorionic gonadotropin and estradiol-17 beta production in the human term placenta.