ARACHIDONIC-ACID AND LIPOXYGENASE PRODUCTS STIMULATE PROTEIN-KINASE CB MESSENGER-RNA LEVELS IN PITUITARY ALPHA-T3-1 CELL-LINE - ROLE IN GONADOTROPIN-RELEASING-HORMONE ACTION

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 pituita ry alpha T3-1 cell line. The addition of AA or its 5-lipoxygenase prod ucts 5-hydroxyeicosatetraenoic acid (5-HETE) or leukotriene C-4 (LTC(4 )) 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 l eukotrienes tested showed no significant effect. The range of effectiv e concentration for LTC(4) and 5-HETE (around 10(-10) M) is the range found in GnRH-stimulated pituitary cells. Although PKC beta mRNA level s were preferentially elevated by LTC(4) and 5-HETE at early time poin ts, PKC alpha mRNA levels were elevated at 6-12 h of incubation when P KC beta mRNA levels returned to basal levels. The addition of the phos pholipase A(2) inhibitor 4-bromophenacyl bromide or the selective 5-li poxygenase inhibitor L-656,224 abolished [D-Trp(6)]GnRH (GnRH-A) eleva tion of PKC beta mRNA levels, whereas PKC alpha mRNA levels were not i ncreased by this neuro-hormone. The cyclo-oxygenase inhibitor indometh acin elevated basal PKC beta mRNA levels and potentiated the GnRH-A re sponse. Cross-talk exists between AA and some of its lipoxygenase prod ucts and PKC beta gene expression during eel signalling. AA, 5-HETE an d LTC(4) participate in the rapid stimulation of PKC beta mRNA levels by GnRH.