Role of arachidonic acid in luteinizing hormone-releasing hormone action: stimulation of progesterone production in rat granulosa cells.

This study investigates the hypothesis that stimulation of ovarian progesterone (P) production by LHRH is mediated in part by arachidonic acid (AA). In rat granulosa cells prelabeled with [3H]AA or [3H]inositol, treatment with LHRH stimulates the accumulation of radiolabeled inositol phosphosphates, diacyglycerol, and unesterified AA. Treatment with AA (3 X 10(-7)-10(-5) M) enhances P production in a dose-dependent manner. Concurrent treatment with AA and LHRH (or a LHRH agonist) further stimulates P production. The stimulatory effect of AA on P production, either alone or in combination with LHRH, could be seen as early as 3 h after AA addition. Addition of a phorbol ester, 12-O-tetracecanoylphorbol-13-acetate (TPA), to granulosa cells stimulates P production. Interestingly, the concomitant presence of AA and TPA further enhances production compared with either TPA or AA treatment alone. The stimulatory effect of AA on P production is completely abolished by nordihydroguaiaretic acid, but not by indomethacin. On the other hand, addition of nordihydroguaiaretic acid (but not indomethacin) reduces LHRH-stimulated P levels by about 50%. Nordihydroguaiaretic acid, as well, markedly attenuates the P response due to combined treatment with LHRH and AA. Taken together, these results strongly support the notion that AA (or its lipoxygenated metabolites) partially mediates the action of LHRH. Along with the calcium and protein kinase-C pathways, AA metabolism may be involved in the biological actions of LHRH in the ovary.