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 microM) 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 45Ca+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.
Ojeda
S R
SR
Negro-Vilar
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008473:Median Eminence / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats
D011458:Prostaglandins E; D007987:Gonadotropin-Releasing Hormone; D000242:Cyclic AMP; D015232:Dinoprostone; D002118:Calcium