Extracellular Calcium Is Required for Copper-Amplified Prostaglandin E2 Stimulation of the Release of Gonadotropin-Releasing Hormone from Median Eminence Explants*

Prostaglandin E2 (PGE2) is known to stimulate the release of LHRH from hypothalamic tissue incubated under in vitro conditions. We have previously shown that a short preincubation of explants of the median eminence area with copper(II) [Cu(II)] complexed to histidine (CuHis) markedly amplifies PGE2 stimulation of LHRH release. In this study, we wished to ascertain if Cu-amplified PGE2 stimulation of LHRH release is dependent on influx of extracellular calcium (Ca) and, if so, whether it is the copper and/or PGE2 action that is Ca dependent. Median eminence area explants were incubated for 5 min with 200 μM CuHis, then for 15 min with 10 μM PGE2, and finally for 45 min in buffer (Cu/PGE2). Controls were incubated with CuHis or PGE2. In the presence of Ca (1.8 mM), Cu/PGE2 stimulation of LHRH release reached a peak value within 15 min of exposure to PGE2 (accelerated phase), after which the rate of release declined, with a half-life of about 20 min (decelerated phase). In the absence of Ca, Cu/PGE2 stimulat...