Time-dependent ovulation inhibition of a selective progesterone-receptor antagonist (Org 31710) and effects on ovulatory mediators in the in vitro perfused rat ovary

Progesterone (P) is one of several local mediators in the ovulatory cascade in the rat. The precise mechanisms of action for P in ovulation and in wha t phase of the ovulatory process P is critical, however, need to be clarifi ed. The present study used a selective P-receptor antagonist, Org 31710, in the in vitro perfused rat ovary model to examine the local role of P and p ossible effects on prostaglandin (PC) and plasminogen-activator (PA) releas e in ovulation. Ovaries from eCG (15 IU)-primed rats were perfused for 20 h with LH (0.2 mug/ml) and 3-isobutyl-1-methylxanthine (IBMX, 200 muM) to in duce ovulation (median = 10.0, 25%-75% range = 8.5-13). Org 31710 was added at either 0, 3.5, 7, or 9 h after LH+IBMX, resulting in significant suppre ssion of ovulation after addition at 0 and 3.5 h (1.0, 1-5.5; and 5.0, 2.5- 7.75 ovulations, respectively) but no suppressive effect when added at late r time points. Progesterone and estradiol levels in the perfusion media wer e increased after LH+IBMX but were not affected by the presence of Org 3171 0. Ovarian tissue levels of PGE(2), PGF(2 alpha), and PA activity were meas ured in ovaries that had been perfused for 10 h, a time that was 2 to 5 h b efore anticipated ovulation. The presence of Org 31710 significantly decrea sed the levels of PGE(2), PGF(2 alpha), and PA activity. These results sugg est that P is essential in ovulation during the initial stages of the ovula tory process. The effect of P to facilitate ovulation seems to relate to st imulation of the PG- and PA-mediator systems.