RU486 inhibits synthesis of an endogenous inhibitor of cell arachidonate release from choriodecidua tissue.
Gravidin is a potent phospholipase A2 inhibitor that may contribute to the maintenance of human pregnancy. The aims of this study were to determine firstly, the site of gravidin synthesis within placental membranes and secondly, whether the antiprogestin compound, RU486, regulates synthesis. Membrane explants were taken from placentae, dissected and cultured in the presence of RU486, progesterone or inhibitors of DNA or protein synthesis and gravidin production was measured by a specific enzyme-linked immunosorbent assay. Production of gravidin was consistently greatest from choriodecidua compared with amnion and decidua. The antibiotics, cycloheximide and actinomycin D inhibited production of gravidin. The progesterone receptor antagonist RU486 at 10(-8) and 10(-7) M reduced gravidin production to 55 and 39% of the control value in membranes cultured after and before the onset of labour respectively. Progesterone at 10(-6) M stimulated gravidin production by 47% after the onset of labour. The increase in gravidin production was correlated with progesterone concentration (r = 0.47, F = 6.38, P = 0.019) in labour tissue. We conclude that the data are consistent with the hypothesis that gravidin production may be partially regulated by progesterone.
Schuster-Woldan
N
N
Department of Obstetrics and Gynaecology, University of Dundee Medical School, Ninewells Hospital, UK.
Hilton
M
M
Wilson
T
T
D000328:Adult; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015153:Blotting, Western; D002823:Chorion / Q000187:drug effects* / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003656:Decidua / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D006727:Hormone Antagonists; D011257:Pregnancy Proteins; C058795:gravidin; D003609:Dactinomycin; D016718:Arachidonic Acid; D015735:Mifepristone; D011374:Progesterone; D003513:Cycloheximide