benzofurans and 5-hydroxy-6-8-11-14-eicosatetraenoic-acid

The cross-talk of arachidonic acid (AA) and its lipoxygenase products with protein kinase C beta (PKC beta) mRNA levels during the action of gonadotropin-releasing hormone (GnRH) was investigated in the pituitary alpha T3-1 cell line. The addition of AA or its 5-lipoxygenase products 5-hydroxyeicosatetraenoic acid (5-HETE) or leukotriene C4 (LTC4) for 30 or 60 min stimulated PCK beta, but not PKC alpha mRNA levels (3-5-fold); PCK gamma is not expressed by the cells. Other HETEs or leukotrienes tested showed no significant effect. The range of effective concentration for LTC4 and 5-HETE (around 10(-10) M) is the range found in GnRH-stimulated pituitary cells. Although PKC beta mRNA levels were preferentially elevated by LTC4 and 5-HETE at early time points, PKC alpha mRNA levels were elevated at 6-12 h of incubation when PKC beta mRNA levels returned to basal levels. The addition of the phospholipase A2 inhibitor 4-bromophenacyl bromide or the selective 5-lipoxygenase inhibitor L-656,224 abolished [D-Trp6]GnRH (GnRH-A) elevation of PKC beta mRNA levels, whereas PKC alpha mRNA levels were not increased by this neurohormone. The cyclo-oxygenase inhibitor indomethacin elevated basal PKC beta mRNA levels and potentiated the GnRH-A response. Cross-talk exists between AA and some of its lipoxygenase products and PKC beta gene expression during cell signalling. AA, 5-HETE and LTC4 participate in the rapid stimulation of PKC beta mRNA levels by GnRH.

Topics: Acetophenones; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Benzofurans; Cell Line; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Gonadotropin-Releasing Hormone; Hydroxyeicosatetraenoic Acids; Indomethacin; Kinetics; Leukotriene C4; Lipoxygenase; Lipoxygenase Inhibitors; Pituitary Gland; Protein Kinase C; Protein Kinase C beta; RNA, Messenger