2ND MESSENGERS AND THE CONTROL OF PROGESTERONE PRODUCTION FROM FIRST-TRIMESTER TROPHOBLAST

Basal progesterone production from first trimester placental cells in culture was high during the first 24 h of culture and fell to less tha n 30% of the initial level after 96 h in vitro. 22(R)-Hydroxycholester ol had a similar effect on progesterone production at all incubation t imes, indicating that the decline in basal steroidogenesis was not due to a loss of mitochondrial or post-mitochondrial enzymes. Continuous stimulation with dibutyryl (db) cyclic AMP maintained progesterone syn thesis at a relatively constant high level despite the fall in basal p rogesterone production, and the optimum concentration of db cyclic AMP was 1.0 mM. The calcium ionophore A23187 had no effect on progesteron e incubation during short-term cultures (<4 h), and inhibited steroido genesis after 24 h. Repeated addition of A23187 during 96 h of culture also inhibited progesterone production. These findings indicate that progesterone production in human trophoblast is supported by a local f actor which maintains a high level of steroid production through a cyc lic AMP-dependent mechanism. The inhibitory effects of calcium ionopho re in trophoblast differ from the stimulatory effects of this compound in other steroidogenic cells, but the reasons for the difference are not known at present. (C) 1997 Elsevier Science Ltd.