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Molecular Human Reproduction, Vol. 7, No. 1, 35-42, January 2001
© 2001 European Society of Human Reproduction and Embryology


Ovary and oogenesis

Inhibition of ovulation in the rat by a leukotriene B4 receptor antagonist

Markus Matousek1,3, Kenrokuro Mitsube2, Masato Mikuni2 and Mats Brännström1

1 Department of Obstetrics and Gynecology, Göteborg University, Göteborg, Sweden, and 2 Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, N-15, W-7, Kita-ku, Sapporo, O60, Japan

Abstract

The involvement of leukotriene (LT) B4 in the ovulatory process of the rat was investigated by the use of a LTB4-receptor antagonist (ZK158252 = L-ANT) administered either intrabursally in vivo or to the in-vitro perfused ovary. The in-vivo experiments revealed inhibition of human chorionic gonadotrophin (HCG)-induced ovulation by 500 µmol/l L-ANT (median 5.5, 25–75% range 1.0–6.0) compared with controls (median 9.0, range 6.25–13.5). In vitro, ovulation was induced by LH (0.2 µg/ml) + 3-isobutyl-1-methylxanthine (IBMX; 0.2 mmol/l). The ovary was perfused either for 20 h, to study ovulation rate, or for 10 h to examine ovarian concentrations of the ovulatory mediators matrix metalloproteinase (MMP)-2 and MMP-9, plasminogen activator (PA), prostaglandin (PG)E2 and PGF2{alpha}. Addition of LH+IBMX resulted in a marked stimulation of steroid release and ovulations occurred in all ovaries (median 11.0, range 10.0–14.0). The L-ANT inhibited ovulation in a dose-dependent way (median 10.0, range 8.0–13.0 at 1 µmol/l; median 6.0, range 3.5–10.0 at 10µmol/l; median 2.0, range 0.75–5.75 at 100 µmol/l). The intra-ovarian activity of PA was increased 1.5-fold by L-ANT (100 µmol/l), but the concentrations of PGE2 and PGF2{alpha} remained unaltered. While no changes in MMP-9 were observed, conversion from pro-MMP-2 to active MMP-2 was inhibited by L-ANT. These results suggest that activation of the LTB4-receptor within the ovary is involved in the ovulatory process and that the effects of LTB4-receptor activation are partly mediated via MMP-2.

leukotriene/matrix metalloproteinase/ovary/ovulation/rat

Notes

3 To whom corresponendence should be adressed at: Department of Obstetrics and Gynecology, Göteborg University, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. E-mail: Markus.Matousek{at}sahlgrenska.se


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