POTENTIAL ROLE FOR ARACHIDONIC-ACID AND EICOSANOIDS IN MODULATING PROGESTERONE SECRETION BY OVINE CHORIONIC CELLS

The present study was conducted to investigate whether arachidonic aci d and its metabolites can modulate progesterone (P4) secretion in ovin e chorionic cells. At concentrations of 7.5 mumol/l and 12.5 mumol/l, arachidonic acid caused an increase of basal P4 secretion (about 1.8-f old (p<0.01) and 2.5-fold (p<0.001), respectively, over control). Such a stimulatory effect was suppressed when the concentration of arachid onic acid attained 25 mumol/l, and at 50 mumol/l the fatty acid led to a decline of basal P4 synthesis (about 35%, p<0.01). Phospholipase A2 (PLA2) and melittin had a similar dual effect to that observed when a rachidonic acid was added exogenously. In contrast, eicosatrienoic aci d (a closely related fatty acid) did not stimulate P4 secretion but in hibited it at a concentration of 50 mumol/l (about 40% inhibition, p<0 .01). The possible involvement of calcium on the effects of arachidoni c acid was explored. Interestingly, 3 mmol/l ethylene glycol bis(beta- aminoethyl ether)-N,N,N,N'-tetraacetic acid (EGTA) and 10 mumol/18-N, N-diethylamino-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) fu rther enhanced the steroidogenic effect of 12.5 mumol/l arachidonic ac id (p<0.05 and p<0.01 vs the corresponding value in the absence of EGT A or TMB-8, respectively). In contrast, these agents failed to modify P4 secretion observed in the presence of 50 mumol/l arachidonic acid. We also tested the effect of inhibition of arachidonic acid metabolism via cyclooxygenase and lipoxygenase pathways. Indomethacin (10 mumol/ l) failed to block the effects of arachidonic acid, but nordihydroguai aretic acid (10 mumol/l) prevented the stimulatory action of this fatt y acid. Taken together, these data suggest that arachidonic acid and i ts metabolites (perhaps its lipoxygenated metabolites) may be importan t intracellular regulators of P4 secretion in ovine chorionic cells.