Interleukin-1 receptor antagonist suppresses human chorionic gonadotropin-induced ovulation in the rat.
Indirect evidence has implicated the interleukin-1 (IL-1) system in ovulation. Thus, the ability of IL-1 beta to induce ovulation in rat and rabbit perfused ovaries has been demonstrated. In the present study, the involvement of the IL-1 system in ovulation was directly tested in vivo, in the rat model. For this purpose, the natural inhibitor of the IL-1 system, interleukin-1 receptor antagonist (IL-1ra), was administered locally by use of an intrabursal injection route. Twenty-six-day-old Sprague-Dawley rats received injections of eCG (10 IU), followed 56 h later by hCG (15 IU). IL-1ra (75 micrograms/bursa) was administered locally into the periovarian sac, 6 h (n = 5), 2 h (n = 11), and 0 h (n = 5) before hCG administration. Control animals (n = 10) received injections of the same volume (50 microliters) of vehicle (PBS). IL-1ra administered locally into the periovarian sac inhibited ovulation from the treated ovary, reaching 40% inhibition (p < 0.05) when injected 2 h prior to hCG, as compared to the untreated contralateral ovary (6 +/- 1.4 ova vs. 10 +/- 1.8 ova) and PBS-injected control ovaries (6 +/- 1.4 ova vs. 8.2 +/- 0.7). Injection of IL-1ra 6 h before or concomitantly with hCG did not affect the ovulation rate. Internucleosomal DNA fragmentation was evaluated by 3' end-labeling and autoradiography for detecting apoptotic changes. No difference in DNA fragmentation was found between treated and untreated ovaries.(ABSTRACT TRUNCATED AT 250 WORDS)
Simón
C
C
Department of Gynecology and Obstetrics, Stanford University Medical Center, California 94305.
Tsafriri
A
A
Chun
S Y
SY
Piquette
G N
GN
Dang
W
W
Polan
M L
ML
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology*; D009707:Nucleosomes / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010060:Ovulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology*
D006063:Chorionic Gonadotropin; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D009707:Nucleosomes; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D004247:DNA