Arachidonic acid and lipoxygenase products stimulate protein kinase Cβ mRNA levels in pituitary αT3-1 cell line: Role in gonadotropin-releasing hormone action

The cross-talk of arachidonic acid (AA) and its lipoxygenase products with protein kinase Cβ (PKCβ) mRNA levels during the action of gonadotropin-releasing hormone (GnRH) was investigated in the pituitary αT3-1 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 PCKβ, but not PKCα mRNA levels (3-5-fold); PCKγ is not expressed by the cells. Other HETEs or leukotrienes tested showed no significant effect. The range of effective concentration for LTC, and 5-HETE (around 10^-10 M) is the range found in GnRH-stimulated pituitary cells. Although PKCβ mRNA levels were preferentially elevated by LTC₄ and 5-HETE at early time points, PKCα mRNA levels were elevated at 6-12 h of incubation when PKCβ 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 PKCβ mRNA levels, whereas PKCα mRNA levels were not increased by this neurohormone. The cyclo-oxygenase inhibitor indomethacin elevated basal PKCβ mRNA levels and potentiated the GnRH-A response. Cross-talk exists between AA and some of its lipoxygenase products and PKCβ gene expression during cell signalling. AA, 5-HETE and LTC₄ participate in the rapid stimulation of PKCβ mRNA levels by GnRH.