The effect of mifepristone (RU486) on the immunohistochemical distribution of prostaglandin E and its metabolite in decidual and chorionic tissue in early pregnancy.
The widespread tissue distribution of prostaglandin dehydrogenase (PGDH), the main enzyme for the metabolism and deactivation of prostaglandin (PG), suggests that local effective levels of PG are controlled by catabolism. Previous reports have suggested that after the administration of mifepristone (RU486) in vivo, the levels of PGDH in uterine tissues fall, such results support earlier suggestions that PGDH is under progesterone control in reproductive tissues. In this study we have used immunohistochemistry to assess tissue concentrations of PGE and its main metabolite 13,14-dihydro-15-keto-PGE in chorionic villi and decidua from women treated with RU486 12, 24, and 36 h previously. In control villous tissue, PGE and 13,14-dihydro-15-keto-PGE2 (PGEM) are prominent in the syncytiotrophoblastic layer, whereas PGE stains only weakly in cytotrophoblasts, due to the presence of PGDH in this region; treatment with RU486 in vivo causes little change in distribution or intensity in villi. However, in decidua, staining for PGE2 was intense in the glands after RU486 and localized in the supranuclear region of the cells. Small blood vessels that were PGE negative and PGEM positive in the controls were PGE positive and PGEM negative in treated tissue. These findings show that PG stimulation by antiprogestin is by means of a direct effect on PGDH, and secondly, that the prominent rise in PGE in blood vessels may be a major mode of action of this steroid in causing abortion, as PGs may synergize with leukocyte chemotactic agents to stimulate neutrophil ingress and tissue destruction.
Cheng
L
L
Medical Research Council Reproductive Biology Unit, University of Edinburgh Center for Reproductive Biology, Scotland.
Kelly
R W
RW
Thong
K J
KJ
Hume
R
R
Baird
D T
DT
D002824:Chorionic Villi / Q000187:drug effects / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003656:Decidua / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D015735:Mifepristone / Q000494:pharmacology*; D011247:Pregnancy; D011458:Prostaglandins E / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism
D011458:Prostaglandins E; D015735:Mifepristone; C025087:15-keto-13,14-dihydroprostaglandin E2; D015232:Dinoprostone