Effects of onapristone on uterine prostaglandin production and plasma progesterone concentrations in guinea-pigs during early and mid-pregnancy.

Onapristone (a progesterone receptor antagonist) administered to guinea-pigs on days 11-14 of pregnancy had no effect on uterine PGF2 alpha output and endometrial PGF2 alpha synthesizing capacity when measured on day 15. Peripheral plasma progesterone concentrations were still high on day 15, although the weight of the conceptuses was decreased by 50%. These findings indicate that the lack of increase in PGF2 alpha production by the uterus during early pregnancy is not due to an inhibitory action of progesterone on uterine PGF2 alpha synthesis and release. The output of PGF2 alpha from the guinea-pig uterus remained low during early pregnancy, showing that the uterus is not the source of increased PGF2 alpha secretion, as indicated previously by an increase in PGF2 alpha metabolite concentrations in the urine, after day 24 of pregnancy. Of the conceptual tissues examined, the fetal placenta had the highest PGF2 alpha synthesizing capacity, and it increased 2.3-fold between days 29 and 36 of pregnancy. The fetal placenta may therefore be the source of increased PGF2 alpha production during pregnancy. Onapristone administered to guinea-pigs on days 27 and 28 or on days 34 and 35 of pregnancy resulted in the guinea-pigs being in the early, middle or late stages of abortion when examined on days 29 or 36, respectively. Increased PG production, particularly of PGF2 alpha, by the uterus occurred in those guinea-pigs that were in the middle or late stages of abortion; uterine PG production in guinea-pigs that were in the early stages of abortion remained low.(ABSTRACT TRUNCATED AT 250 WORDS)