REVERSIBILITY OF ANTIGESTAGENIC ACTION OF ANTIPROGESTIN ONAPRISTONE BY EXOGENOUS PROGESTAGENS DURING EARLY-PREGNANCY IN GUINEA-PIG

Ability of progesterone, gestodene, promegestone and cyproterone aceta te (CPA) to reverse antigestagenic action of onapristone in adult fema le guinea pigs was investigated. Onapristone (10 mg/kg, s.c.) administ ered on post-conception days 8-11 caused resorption of implantations a nd vaginal bleeding in all animals. Simultaneous administration of pro gesterone, gestodene or promegestone on days 7-13 successfully reverse d antigestagenic action of this antiprogestin, since most animals supp lemented with these progestagens had viable implantations at autopsy o n day 14. CPA was, however, ineffective and animals supplemented with it had only resorbed implantations and blood in uterus and vagina like that in onapristone per se treated animals. High plasma progesterone and low PGFM concentration were generally observed in all pregnant ani mals bearing viable implantations. PGFM (13, 14-dihydro-15-keto PGF(2 alpha)) was significantly elevated by day 14 in onapristone-treated (G roup II) and CPA-supplemented (Group X) animals. No discernible effect on pregnancy or post-implantation embryonic development was observed in animals treated per se with these progestagens.