EFFECTS OF ONAPRISTONE ON UTERINE PROSTAGLANDIN PRODUCTION AND PLASMAPROGESTERONE CONCENTRATIONS IN GUINEA-PIGS DURING EARLY AND MID-PREGNANCY

Onapristone (a progesterone receptor antagonist) administered to guine a-pigs on days 11-14 of pregnancy had no effect on uterine PGF(2 alpha ) output and endometrial PGF(2 alpha) synthesizing capacity when measu red on day 1.5. Peripheral plasma progesterone concentrations were sti ll high on day 15, although the weight of the conceptuses was decrease d by 50%. These findings indicate that the lack of increase in PGF(2 a lpha) production by the uterus during early pregnancy is not due to an inhibitory action of progesterone on uterine PGF(2 alpha) synthesis a nd release. The output of PGF(2 alpha) from the guinea-pig uterus rema ined low during early pregnancy, showing that the uterus is not the so urce of increased PGF(2 alpha) secretion, as indicated previously by a n increase in PGF(2 alpha) metabolite concentrations in the urine, aft er day 24 of pregnancy. Of the conceptual tissues examined, the fetal placenta had the highest PGF(2 alpha) synthesizing capacity, and it in creased 2.3-fold between days 29 and 36 of pregnancy. The fetal placen ta may therefore be the source of increased PGF(2 alpha) production du ring pregnancy. Onapristone administered to guinea-pigs on days 27 and 28 or on days 34 and 35 of pregnancy resulted in the guinea-pigs bein g in the early, middle or late stages of abortion when examined on day s 29 or 36, respectively. Increased PG production, particularly of PGF (2 alpha), by the uterus occurred in those guinea-pigs that were in th e middle or late stages of abortion; uterine PG production in guinea-p igs that were in the early stages of abortion remained low. Peripheral concentrations of plasma progesterone remained high in guinea-pigs in the early and middle stages of abortion but fell by 70% in those guin ea-pigs in the late stages of abortion. These results indicate that in creased uterine PG production following onapristone treatment in mid-p regnancy occurs as a result of the abortion process and is not respons ible for the initiation of pregnancy termination.