CHARACTERIZATION OF LEUKOTRIENE-C4 BINDING IN ANTERIOR-PITUITARY MEMBRANE PREPARATIONS

Pituitary cells produce leukotrienes (LTs) and respond to exogenous administration of LTs by releasing gonadotropins. Specific high affinity leukotriene C4(LTC4) binding has been found in membrane preparations of bovine anterior pituitaries. Unlabelled LTC4 displaced specific [H-3]LTC4 binding. Other leukotrienes (LTB4, LTD4, LTE4, LTF4) did not compete with [H-3]LTC4 for binding sites when administered at increasing concentrations together with a constant amount of radioligand indicating that the binding is highly specific for LTC4. Scatchard analysis of binding data obtained from saturation studies revealed a single binding site for [H-3]LTC4 with a Kd of 8.95 +/- 5.53 nM and a B max of 15.44 +/- 6.93 pmol per mg of membrane protein. Glutathione S-transferase, a possible LTC4 binding site, did not display activity in the membrane fraction although the two glutathione derivates S-octylglutathione and S-decylglutathione competed with LTC4 in binding experiments. As leukotrienes are potent stimulators of gonadotropin secretion and modulators of gonadotropin-releasing hormone (GnRH)-induced gonadotropin release it is concluded that leukotrienes may be involved in the signal transduction pathway of GnRH and that they may act via a specific and high affinity receptor.