INHIBITORY EFFECT OF LEUKOTRIENES ON LUTEINIZING-HORMONE RELEASE

The aim of this work was to study the effect of high concentrations of leukotrienes on luteinizing hormone (LH) secretion in rat anterior pi tuitary cells. We also investigated the effect of leukotrienes in para llel with gonadotropin-releasing hormone (GnRH) action. Experiments we re on cells gained from trypsinized pituitaries of female rats. Tests were performed by superfusion of the cells attached to cytodex-1 carri er beads. The LH content in samples of perfusate was estimated by radi oimmunoassay. This work reports 48% inhibition of basic LH release by action of leukotriene C-4 in superfused cells when applied continuousl y at a concentration of 100 nmol/l. Moreover, we have shown that leuko trienes suppressed GnRH-induced LH secretion in rat pituitary cells wh en applied in parallel to GnRH (1 nmol/l) as a 4-min pulse at a concen tration of 0.1 nmol/l. GnRH-induced LH release was reduced to 66% of i ts value by leukotriene (LT) B-4 (0.1 nmol/l) action; also to 54% by L TC4, 66% by LTD4 and 74% by LTE4 action. In contrast, arachidonic acid (50 pmol/l) and its other 5-lipoxygenase metabolites: 5-hydroperoxyei cosatetraenoic acid (5-HPETE) (50 pmol/l), or 5-hydroxyeicosatetraenoi c acid (5-HETE) (50 pmol/l), had no inhibitory effect on GnRH-induced LH release. Arachidonic acid and 5-HETE potentiated GnRH-induced LH re lease up to 249% and 429%, respectively, when applied in parallel with GnRH (1 nmol/l) as a 4-min pulse at a concentration of 10 pmol/l. In our earlier work we have shown that several leukotrienes are potent st imulants of LH release. The present report documents the finding that the 5-lipoxygenase pathway is also involved in the inhibitory regulati on of hormone release in anterior pituitary cells.