title: Arachidonic acid and lipoxygenase products stimulate protein kinase C beta mRNA levels in pituitary alpha T3-1 cell line: role in gonadotropin-releasing hormone action.
abstract: 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.
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: Z
authors.initials: Z
authors.lastname: Shraga-Levine
authors.forename: D
authors.initials: D
authors.lastname: Ben-Menahem
authors.forename: Z
authors.initials: Z
authors.lastname: Naor
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology; D002460:Cell Line; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D017997:Leukotriene C4 / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D010902:Pituitary Gland / Q000201:enzymology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D064546:Protein Kinase C beta; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001572:Benzofurans; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D012333:RNA, Messenger; C055868:L 656224; D016718:Arachidonic Acid; D017997:Leukotriene C4; D007987:Gonadotropin-Releasing Hormone; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D008084:Lipoxygenase; D011493:Protein Kinase C; D064546:Protein Kinase C beta; C006821:4-bromophenacyl bromide; D007213:Indomethacin