INTERLEUKIN-1-BETA INHIBITS PROGESTERONE ACCUMULATION IN RAT CORPORA LUTEAL CELL-CULTURES IN A MECHANISM DISSOCIATED FROM ITS EFFECTS ON NITRIC-OXIDE AND PROSTAGLANDIN-E ACCUMULATION

The objective of this study was to examine the effect of interleukin-1 beta (IL-1) on progesterone (P) biosynthesis and the potential interm ediary involvement of prostaglandin (PG) E and nitric oxide (NO) in P accumulation in PMSG/hCG-primed rat corpora luteal (CL) cell cultures. Exposure of primed CL cells to IL-1 (10 ng/ml) for 48 h resulted in a 65-86% reduction (P < 0.01) in P accumulation concurrent with a 2-3.4 -fold increase in PGE content, a 70% increase in PGF(2x) content and a 1.9-3.3-fold increase in nitrite generation. These effects were aboli shed by the IL-1 receptor antagonist, suggesting specific IL-1 recepto r-mediated effects. Indomethacin, a cyclooxygenase inhibitor, abolishe d PGE and PGF(2x) production and attenuated the basal (but not IL-1-st imulated) accumulation of P. N-G-Nitro-L-arginine (NNLA), a competitiv e inhibitor of nitrite synthesis, slightly reduced basal P accumulatio n but had no effect on IL-1-induced suppression of P accumulation. NNL A reduced basal PGE accumulation and IL-1-stimulated PGE accumulation (55 and 61% respectively). Transforming growth factor beta 1 (TGF-beta 1; 10 ng/ml) significantly attenuated the IL-1-stimulated PGE and NO production (61 and 42%, respectively), but did not affect the ability of IL-1 to suppress P accumulation. Thus, NO, PGF(2x), and PGE are not obligatory intermediaries of IL-1-mediated suppression of P accumulat ion in rat CL, but are involved in basal P biosynthesis and NO seems t o have a regulatory role in the biosynthesis of PGE. The present obser vations suggest a pleiotropic response of PMSG/hCG-primed CL cells to IL-1, characterized by an independent suppression of P accumulation an d a concomitant increase in NO, PGF(2x) and PGE generation. Since IL-1 attenuates P accumulation, these findings may imply a direct autocrin e/paracrine function for IL-1 in the maintenance or the demise of rat CL. (C) 1997 Elsevier Science Ireland Ltd.