Regulation of luteal prostaglandin F2α 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 F2α (PGF2α) 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 PGF2α secretion. Cytokines, tumor necrosis factor α (TNFα) or interferon γ (IFNγ) alone had no or modest regulatory effects. Arachidonyl trifluoromethyl ketone (AACOCF3), a specific group IVA phospholipase A2 inhibitor, depressed both basal and cytokine-regulated PGF2α production. A combination of TNFα and IFNγ stimulated PGF2α synthesis and cytotoxicity (both, P < 0.05). Agonistic anti-Fas antibody challenge caused a significant cytotoxic effect but without affecting PGF2α production. The present data suggest that P4 inhibits and TNFα and IFNγ cooperatively stimulate PGF2α release by rat luteal cells. They also suggest that luteal cell death induced by TNFα/IFNγ and Fas stimulation seems to occur via distinct signaling pathways involving PGF2α production.