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Biology of Reproduction 63, 1642-1647 (2000)
© 2000 Society for the Study of Reproduction, Inc.


Regular Article

Time-Dependent Ovulation Inhibition of a Selective Progesterone-Receptor Antagonist (Org 31710) and Effects on Ovulatory Mediators in the In Vitro Perfused Rat Ovary1

Marita Pall2,a, Masato Mikunia, Kenrokuro Mitsubea, and Mats Brännströma

a Department of Obstetrics and Gynecology, Göteborg University, S-41345 Göteborg, Sweden

ABSTRACT

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 what phase of the ovulatory process P is critical, however, need to be clarified. 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 possible effects on prostaglandin (PG) and plasminogen-activator (PA) release in ovulation. Ovaries from eCG (15 IU)-primed rats were perfused for 20 h with LH (0.2 µg/ml) and 3-isobutyl-1-methylxanthine (IBMX, 200 µM) to induce 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 suppression 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 later time points. Progesterone and estradiol levels in the perfusion media were increased after LH+IBMX but were not affected by the presence of Org 31710. Ovarian tissue levels of PGE2, PGF2{alpha}, and PA activity were measured in ovaries that had been perfused for 10 h, a time that was 2 to 5 h before anticipated ovulation. The presence of Org 31710 significantly decreased the levels of PGE2, PGF2{alpha}, and PA activity. These results suggest that P is essential in ovulation during the initial stages of the ovulatory process. The effect of P to facilitate ovulation seems to relate to stimulation of the PG- and PA-mediator systems.

FOOTNOTES

First decision: 11 April 2000.

1 Supported by grants from the Swedish Medical Research Council (11607 to M.B.), Hjalmar Svensson Foundation, and Medical Faculty of Göteborg University.

2 Correspondence: Marita Pall, Department of Obstetrics and Gynecology, Göteborg University, Sahlgrenska University Hospital, S-41345 Göteborg, Sweden. FAX: 46 31 829248; mspall{at}hotmail.com




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