Interleukin-1β inhibits luteinizing hormone-induced plasminogen activator activity in rat preovulatory follicles in vitro

Abstract

The effects of interleukin-1β (IL-1β) and tumour necrosis factor-α (TNFα) on ovulation-associated plasminogen activator (PA) activity were investigated using preovulatory follicles excised 48h after equine chorionic gonadotrophin (16IU)-priming of immature rats. Follicles were incubated for 6 and 14h with a single dose of LH (1 μg/ml) only, or various cytokine doses in the presence or absence of LH. PA activity in follicular homogenates was determined by a radioactively labelled fibrin-coated plate method and secreted levels of the ovulatory mediators progesterone (P) and prostaglandin E (PGE) were measured by radioimmunoassay. LH induced timedependent rises in PA (2.5-fold over control at 6h and fourfold over control at 14h), while IL-1β and TNFα alone had no effect over either time period. LH and cytokine coincubations over 14h revealed that IL-1β dosedependently inhibited the LH-induced increase in PA activity, up to 85%. The effects of TNFα on LH-induced PA activity were not significant. Both IL-1β and TNFα increased P and PGE secretion time- and dose-dependently. In summary, IL-1β dose-dependently inhibits the LH-induced increase in PA activity in rat preovulatory folliclesin vitro while, as with TNFα, increasing P and PGE synthesis. This study, shows that the earlier reported pro-ovulatory action of IL-1β is not likely to be mediated by activation of the PA-system and suggests that IL-1β may mediate a regulatory loop controlling the extent and distribution of LH-induced PA activity in rat preovulatory follicles.