Prostaglandin E₂-induced luteinizing hormone-releasing hormone release involves mobilization of intracellular Ca⁺²

The present in vitro experiments were performed to examine the involvement of Ca⁺² in the mechanism by which prostaglandin E₂ (PGE₂) induces LHRH release from the median eminence (ME) of the hypothalamus. Stepwise decreases in the Ca⁺² concentration of the incubation medium reduced the LHRH response to PGE₂. Nevertheless, neither complete omission of Ca⁺² (residual Ca⁺² concentration, 3.5 μM) nor chelation of residual Ca⁺² with EGTA prevented the stimulatory effect of the PG, suggesting that a significant portion of the PGE₂ effect on LHRH release is independent of extracellular Ca⁺². Blockade of Ca⁺² influx with verapamil, a Ca⁺² entry blocker, demonstrated that this component of the PGE₂ effect is completely independent of inward Ca⁺² movement. Depletion of intraterminal Ca⁺² stores by exposure of the MEs to the Ca⁺² ionophore A23187 in medium without Ca⁺² containing EGTA almost completely obliterated the subsequent LHRH response to PGE₂, indicating that normal intraterminal Ca⁺² levels are important for the PGE₂ effect to occur. Preloading the ME terminals with ⁴⁵Ca⁺² and subsequent stimulation with PGE₂ demonstrated that even in the absence of extracellular Ca⁺², PGE₂ stimulates Ca⁺² efflux from the terminals, and this Ca⁺² movement occurs temporarily associated with LHRH release. Depolarization of ME terminals with 56 mM K⁺ in the presence of normal Ca⁺² concentration resulted in massive efflux of ⁴⁶Ca⁺² and a greater LHRH response than that produced by PGE₂, suggesting that the effect of PGE₂ is not the consequence of a nonspecific general depolarization of ME nerve terminals. Thus, although a full LHRH response to (exogenous) PGE₂ necessitates normal extraterminal Ca⁺² concentrations, the results indicate that translocation of Ca⁺² from intracellular stores is an event involved in the mechanism by which PGE₂ releases LHRH.