Potential role for arachidonic acid and eicosanoids in modulating progesterone secretion by ovine chorionic cells.
The present study was conducted to investigate whether arachidonic acid and its metabolites can modulate progesterone (P4) secretion in ovine 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-fold (p < 0.01) and 2.5-fold (p < 0.001), respectively, over control). Such a stimulatory effect was suppressed when the concentration of arachidonic 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 arachidonic acid was added exogenously. In contrast, eicosatrienoic acid (a closely related fatty acid) did not stimulate P4 secretion but inhibited it at a concentration of 50 mumol/l (about 40% inhibition, p < 0.01). The possible involvement of calcium on the effects of arachidonic acid was explored. Interestingly, 3 mmol/l ethylene glycol bis(beta-aminoethyl ether)-N,N,N,N'-tetraacetic acid (EGTA) and 10 mumol/l 8-N,N-diethylamino-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) further enhanced the steroidogenic effect of 12.5 mumol/l arachidonic acid (p < 0.05 and p < 0.01 vs the corresponding value in the absence of EGTA 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 nordihydroguaiaretic acid (10 mumol/l) prevented the stimulatory action of this fatty acid.(ABSTRACT TRUNCATED AT 250 WORDS)
de la Llosa-Hermier
M P
MP
Laboratoire de Biochimie des Hormones, CNRS, Gif-sur-Yvette, France.
Fernandez
C
C
Martal
J
J
Hermier
C
C
D000485:Allergens / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000502:physiology; D002823:Chorion / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D015777:Eicosanoids / Q000494:pharmacology*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D008555:Melitten / Q000494:pharmacology; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D011374:Progesterone / Q000378:metabolism*; D012756:Sheep
D000485:Allergens; D002121:Calcium Channel Blockers; D015777:Eicosanoids; D008555:Melitten; D016718:Arachidonic Acid; D011374:Progesterone; D004533:Egtazic Acid; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D009637:Masoprocol; D002786:Cholesterol Side-Chain Cleavage Enzyme; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium; D007213:Indomethacin