The mechanisms of action of progesterone and the anti-progestin ZK 98734 on PGF2 alpha synthesis by early human decidua.
The inhibition of prostaglandin (PG) synthesis found in early human decidua is antagonized by the anti-progestin, ZK 98734. This action of ZK 98734 is abolished by actinomycin, an inhibitor of protein synthesis and by the calcium channel blocker, verapamil. Calmidazolium, an antagonist of the intracellular calcium binding protein calmodulin was less effective in inhibiting the stimulation of PG synthesis induced by the anti-progestin. Chronic stimulation of protein kinase C activity by 1-oleoyl-2-acetyl-sn-glycerol (OAG) induced a slight reduction of PG release and was antagonized by polymixin. These findings suggest that inhibition of PG synthesis in early pregnancy is caused by progesterone and that increased release of PGs induced by anti-progestins is dependent on new protein formation and requires extracellular calcium.
Smith
S K
SK
MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, U.K.
Kelly
R W
RW
D000022:Abortion, Spontaneous; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D003656:Decidua / Q000187:drug effects / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis*; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000037:antagonists & inhibitors*; D011863:Radioimmunoassay; D014700:Verapamil / Q000494:pharmacology
D002147:Calmodulin; D004075:Diglycerides; D004963:Estrenes; D007093:Imidazoles; D011372:Progestins; D003609:Dactinomycin; C048260:lilopristone; D011374:Progesterone; C031938:calmidazolium; C038237:1-oleoyl-2-acetylglycerol; D015237:Dinoprost; D014700:Verapamil