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The rat ovarian perfusion model with bursa removed and intact was used to further characterize the effects of interleukin-1 beta (IL-1 beta) and the natural IL-1 receptor anatagonist (IRAP) on ovulation, steroidogenesis, and prostaglandin production. Twenty-six- to 27-day-old female Sprague-Dawley rats were injected sc with 25 IU PMSG, and 48 h later, the right ovary was dissected (with bursa removed and intact for various experiments) and placed in the perfusion chamber. Ovaries were exposed to various doses of IL-1 beta alone, IL-1 beta with LH, and IL-1 beta with LH and isobutylmethylxanthine (IBMX). The natural IL-1 receptor antagonist was also added to the chambers with LH and IBMX. IL-1 beta at 0.8 (n = 3) and 8.0 (n = 4) nM did not induce LH-independent ovulation in PMSG-stimulated ovaries with bursa removed. In bursa-intact perfusions (n = 3), one ovulation was produced in each compared to control ovaries with bursa intact (n = 3) given an ovulatory trigger of LH alone [2.3 +/- 0.6 (+/- SD) ovulations; P < 0.02]. IL-1 beta enhanced, in a dose- and gonadotropin-dependent fashion, the production of prostaglandin E2 (PGE2) in PMSG-stimulated ovaries with bursa removed given an ovulatory trigger of LH and IBMX compared to that in controls. PGF2 alpha and 6-keto-PGF1 alpha were also modulated by IL-1 beta. Estradiol and progesterone production were not affected. The natural IRAP inhibited ovulation (7.8 +/- 3.9 ovulations vs. 12.4 +/- 1.5; P < 0.04) in PMSG-stimulated ovaries given LH and IBMX as the ovulatory trigger compared to that in controls. This inhibition of ovulation was not associated with reduced steroid or PG levels. IL-1 beta appears to play a potentially significant role in the process of ovulation. The functional importance of the bursa in this model is highlighted in this study. IL-1 beta modulates PG, but not steroid, production. IRAP inhibited ovulation without significantly affecting PG or steroid production.

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