title: Arachidonic acid as a stimulatory mediator of luteinizing hormone-releasing hormone action in the rat ovary.
abstract: The present study further examined the role of arachidonic acid (AA) in the action of LHRH on ovarian steroidogenesis. Rat granulosa cells were incubated with LHRH and/or AA in the presence of FSH for 24 h. As expected, the presence of LHRH markedly attenuated the FSH-induced progesterone (P) production. AA by itself did not affect the magnitude of P production induced by FSH. However, when AA (10(-5) M) was added during the last 6 h to the cultures containing LHRH and FSH, AA partially reversed the inhibitory action of LHRH (by 42%). Likewise, addition of AA partially antagonized the inhibitory effect of 12-O-tetradecanoylphorbol-13-acetate (TPA; 10(-9) M) on FSH-induced P production (by 71%). Pretreatment of granulosa cells with TPA or LHRH without FSH for 18 h did not alter the stimulatory effect of AA on P formation during the subsequent 6-h culture period. In other experiments granulosa cells were incubated for 5 h in the absence of FSH. Treatment with AA, TPA, or LHRH alone caused significant increase in P production. Combined treatment with AA and LHRH or AA plus TPA showed additive effects on P formation. By contrast, AA failed to potentiate the effect of LHRH or TPA on 20 alpha-hydroxyprogesterone accumulation. Although AA by itself slightly stimulated 20 alpha-hydroxyprogesterone production, the magnitude was much less than that induced by TPA or LHRH. When 25-hydroxycholesterol was present in the incubation medium, P production was significantly increased. In the presence of 25-hydroxycholesterol, AA further increased P formation, but did not enhance the stimulatory actions of LHRH or TPA in this regard. Taken together, these results further support the hypothesis that AA (or its metabolites) play a stimulatory role in the direct action of LHRH on ovarian steroidogenesis.
authors.affiliation: Department of Obstetrics and Gynecology, University of British Columbia, Grace Hospital, Vancouver, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: P C
authors.initials: PC
authors.lastname: Leung
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology* / Q000502:physiology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D002784:Cholesterol / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D006107:Granulosa Cells / Q000378:metabolism / Q000502:physiology; D010053:Ovary / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001095:Arachidonic Acids; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D002772:Cholera Toxin; D002784:Cholesterol; D013755:Tetradecanoylphorbol Acetate