A role for extracellular copper in modulating prostaglandin E2 (PGE2) action: facilitation of PGE2 stimulation of the release of gonadotropin-releasing hormone (LHRH) from median eminence explants.

Copper is present in high concentrations in axonal terminals of hypothalamic neurons (1). We have previously postulated that copper is released from axonal terminals of hypothalamic neurons (2). In this study, we addressed the question: Does extracellular copper facilitate PGE2 action, specifically, the stimulation of LHRH release? The median eminence area (MEA) of male rats was incubated under in vitro conditions, and LHRH release into the medium was quantified by RIA. When MEA were incubated for 5 min with 100 microM copper and then for 15 min with 50 microM PGE2 (Cu/PGE2), Cu/PGE2-stimulated release of LHRH was significantly (P less than 0.001) greater (2 times) than the sum of copper- and PGE2-stimulated release. When MEA were first incubated for 15 min with PGE2 and then for 5 min with copper (PGE2/Cu), PGE2/Cu-stimulated release equalled the sum of PGE2- and copper-stimulated release of LHRH. Thus, copper facilitates PGE2 stimulation of LHRH release from the MEA, and the characteristics of this facilitation are consistent with an enhancement of PGE2 binding to its receptor. These results support the proposition that extracellular copper can serve as a modulator of PGE2 action.