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

• Published in: Biology of reproduction 2000-12, Vol.63 (6), p.1642-1647
• Main Authors: PALL, Marita, MIKUNI, Masato, MITSUBE, Kenrokuro, BRÄNNSTRÖM, Mats
• Format: Article
• Language: English
• Subjects: 1-Methyl-3-isobutylxanthine - metabolism; Animals; Biological and medical sciences; Dinoprostone - biosynthesis; Estradiol - biosynthesis; Estrenes - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Furans - pharmacology; Hormone metabolism and regulation; In Vitro Techniques; Luteinizing Hormone - biosynthesis; Mammalian female genital system; Ovary - drug effects; Ovulation - drug effects; Plasminogen Activators - metabolism; Progesterone - biosynthesis; Prostaglandins - biosynthesis; Rats; Rats, Sprague-Dawley; Receptors, Progesterone - antagonists & inhibitors; Time Factors; Vertebrates: reproduction
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod63.6.1642

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 PGE 2 , PGF 2α , 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 PGE 2 , PGF 2α , 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.