DECIDUAL ADENYLATE-CYCLASE AND PROSTAGLANDIN PRODUCTION IN-VITRO

Human decidua contains an active adenylate cyclase, and a number of st udies indicate that adenylate cyclase is functionally linked to increa sed in vitro prostaglandin synthesis. Increased decidual prostaglandin synthesis is associated with parturition, and therefore activation of adenylate cyclase may be involved in the control of human parturition . In this study, third trimester human decidual cells were preincubate d for no more than 24 h prior to stimulation with a number of reagents which increase cellular cyclic AMP levels. Forskolin rapidly increase d intracellular and extracellular cyclic AMP levels, but there was no increase in prostaglandin E(2) biosynthesis during incubations ranging from 5 min up to 24 h. Dibutyryl cyclic AMP or 8-bromo-cyclic AMP wer e also without effect on PGE(2) production, which suggests that the ad enylate cyclase was not linked to the mechanisms regulating prostaglan din production. Cholera toxin increased basal cyclic AMP and PGE(2) sy nthesis, and was without effect: on IL-1 beta-stimulated PGE(2) levels . PGE(2) synthesis was increased by 24 h culture with IL-1 beta in all the cell preparations, indicating that the cells were biologically ac tive, and that the lack of effect of changes in cyclic AMP synthesis o n PGE(2) levels could not be attributed to a defect in the prostagland in synthetic pathway. Our findings did not agree with earlier work whi ch showed that changes in cyclic AMP were correlated with changes in P GE(2) production by human decidual cells. it is clear that in the prev ious studies the decidual cells were preincubated for 4-7 days prior t o stimulation, in contrast with 24 h in our investigation. We suggest that the functional link between cyclic AMP and PGE(2) synthesis repor ted previously may develop during culture, and not be a part of normal decidual cell function, but further studies are needed to test this h ypothesis.