Interleukin-1 beta (IL-1 beta) modulates prostaglandin production and the natural IL-1 receptor antagonist inhibits ovulation in the optimally stimulated rat ovarian perfusion model

Abstract

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.