Regulation of luteal prostaglandin F(2 alpha) production and its relevance to cell death: an in vitro study using rat dispersed luteal cells

We investigated the mechanism by which rat luteal cells produce prostaglandin F(2 alpha) (PGF(2 alpha)) and its relevance to cell death in vitro. Treatment with progesterone (P4) of dispersed luteal cells prepared from rats on day 9 of pseudopregnancy caused dose-dependent inhibition of PGF(2 alpha) secretion. Cytokines, tumor necrosis factor alpha (TNFalpha) or interferon gamma (IFN gamma) alone had no or modest regulatory effects. Arachidonyl trifluoromethyl ketone (AACOCF(3)), a specific group IVA phospholipase A(2) inhibitor, depressed both basal and cytokine-regulated PGF(2 alpha) production. A combination of TNFalpha and IFN gamma stimulated PGF(2 alpha) synthesis and cytotoxicity (both, P<0.05). Agonistic anti-Fas antibody challenge caused a significant cytotoxic effect but without affecting PGF(2 alpha) production. The present data suggest that P4 inhibits and TNFalpha and IFN gamma cooperatively stimulate PGF(2 alpha) release by rat luteal cells. They also suggest that luteal cell death induced by TNFalpha/IFN gamma and Fas stimulation seems to occur via distinct signaling pathways involving PGF(2 alpha) production.