Diacylglycerol and phorbol esters enhance LHRH and prostaglandin E2 secretion from median eminence nerve terminals in vitro.

The present experiments were designed to evaluate the role of protein kinase C activation on the secretion of the neural peptide, LHRH, from hypothalamic nerve terminals in vitro. Two specific protein kinase C activators, diacylglycerol (1,2-didecanoylglycerol, DiC10) and a phorbol ester (12,13-dibutyrate, PDBu) were used as probes. In addition to LHRH, secretion of prostaglandin E2 (PGE2) was also measured, since previous studies from our laboratory indicate that this arachidonic acid metabolite is intimately involved in the LHRH secretory process. PDBu at a dose of 200 nM significantly enhanced LHRH secretion from median eminence nerve terminals; in addition, a more modest but significant stimulation of PGE2 release was also observed. DiC10 (100 microM), on the other hand, enhanced PGE2 release but had no clear effect on LHRH secretion. Release of LHRH, however, was clearly stimulated when the lipoxygenase inhibitor nordihydroguaiaretic acid was added to the medium, suggesting that some arachidonic acid metabolites are inhibitory to LHRH secretion. The results indicate that protein kinase C activation leads to an enhanced secretion of LHRH. In addition, they suggest that 1,2-diacylglycerol may also activate the formation of arachidonoyl residues inhibitory to LHRH release.