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 LTC4 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.
Stimulation of Jun N-Terminal Kinase (JNK) by Gonadotropin-Releasing Hormone in Pituitary αT3–1 Cell Line Is Mediated by Protein Kinase C, c-Src, and CDC42