INTERLEUKIN-1-BETA (IL-1-BETA) MODULATES PROSTAGLANDIN PRODUCTION ANDTHE NATURAL IL-1 RECEPTOR ANTAGONIST INHIBITS OVULATION IN THE OPTIMALLY STIMULATED RAT OVARIAN PERFUSION MODEL

The rat ovarian perfusion model with bursa removed and intact was used to further characterize the effects of interleukin-1beta (IL-1beta) a nd the natural IL-1 receptor anatagonist (IRAP) on ovulation, steroido genesis, and prostaglandin production. Twenty-six- to 27-day-old femal e 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 var ious experiments) and placed in the perfusion chamber. Ovaries were ex posed to various doses of IL-1beta alone, IL-1beta with LH, and IL-1be ta with LH and isobutylmethylxanthine (IBMX). The natural IL-1 recepto r antagonist was also added to the chambers with LH and IBMX. IL-1beta at 0.8 (n = 3) and 8.0 (n = 4) nm did not induce LH-independent ovula tion in PMSG-stimulated ovaries with bursa removed. In bursa-intact pe rfusions (n = 3), one ovulation was produced in each compared to contr ol ovaries with bursa intact (n = 3) given an ovulatory trigger of LH alone [2.3 +/- 0.6 (+/- SD) ovulations; P < 0.02]. IL-1beta enhanced, in a dose- and gonadotropin-dependent fashion, the production of prost aglandin E2 (PGE2) in PMSG-stimulated ovaries with bursa removed given an ovulatory trigger of LH and IBMX compared to that in controls. PGF 2alpha and 6-keto-PGF1alpha were also modulated by IL-1beta. Estradiol and progesterone production were not affected. The natural IRAP inhib ited 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 com pared to that in controls. This inhibition of ovulation was not associ ated with reduced steroid or PG levels. IL-1beta appears to play a pot entially significant role in the process of ovulation. The functional importance of the bursa in this model is highlighted in this study. IL -1beta modulates PG, but not steroid, production. IRAP inhibited ovula tion without significantly affecting PG or steroid production.