Stimulation of progesterone and prostaglandin E 2 production by lipoxygenase metabolites of arachidonic acid

The role of several lipoxygenase metabolites of arachidonic acid in the action of luteinizing homone-releasing hormone (LHRH) on ovarian hormone production was investigated. Like LHRH, treatment of rat granulosa cells with 5-HETE, 5-HPETE, 12-HETE, 15-HETE or 15-HPETE stimulated progesterone (P) and prostaglandin E 2 (PGE 2) production. 12-HEPE was most potent and stimulated P and PGE 2 equally well. By contrast, 5-HETE stimulated P better than PGE 2, while 15-HETE was a potent stimulator of PGE 2 but not of P. Stimulation of P and PGE 2 by LHRH or 12- O-tetradecanoylphorbol 13-acetate (TPA) was further augmented by several HETEs and HPETEs. Like protein kinase C, arachidonic acid metabolites appear to mediate the multiple actions of LHRH in the ovary.