THE DELTA-OPIOID SIGNAL-TRANSDUCTION ON THE GONADOTROPIN-RELEASING-HORMONE RELEASE IS EICOSANOID DEPENDENT

In static incubations, the K+ induced release of gonadotropin-releasin g hormone (GnRH) and of prostaglandin (PG) E2, was 2-3 times higher in the isolated median eminence (ME) compared to the hypothalamic area c ontaining the arcuate nucleus (ARN) plus the ME. The delta-opioid agon ist DTLET, induced a parallel, dose-dependent reduction of GnRH and PG E2 release in the ARN plus ME. Both effects of DTLET were blocked by t he delta-opioid antagonist Diallyl-G. In the isolated ME, DTLET reduce d the secretion of PGE2 but enhanced the release of GnRH. In this area Diallyl-G had no effect on the PGE2 release but blocked the GnRH secr etion. When the PGE2 production was blocked by indomethacin in the ARN plus ME preparation, DTLET increased the release of GnRH and induced the production of leukotrienes (LTs). On the other hand, DTLET decreas ed the release of both GnRH and PGE2 in the presence of nordihydroguai aretic acid (NDGA), an inhibitor of the production of LTs. The above r esults suggest that: (a) the delta-opioid agonist DTLET modulates GnRH release differentially in the hypothalamic areas examined; and (b) th e arachidonic acid metabolites are involved in the mode of action of D TLET on the release of GnRH in the ARN plus ME hypothalamic fragment.