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. 1987 Jan;84(2):580–584. doi: 10.1073/pnas.84.2.580

Copper amplification of prostaglandin E2 stimulation of the release of luteinizing hormone-releasing hormone is a postreceptor event.

A Barnea, G Cho
PMCID: PMC304254  PMID: 2432612

Abstract

We have shown that copper amplifies prostaglandin E2 (PGE2) stimulation of luteinizing hormone-releasing hormone (LH-RH) from explants of the median eminence area (MEA) and that this process is calcium-dependent. Since a Ca-cAMP pathway has been implicated in PGE2 action on the LH-RH neuron, in this study we wished to ascertain if copper exerts its effect on the PGE2 receptor or on a postreceptor component involved in PGE2 action. MEA of adult male rats were incubated for 5 min with 200 microM Cu/histidine (CuCl2 mixed with L-histidine at an equimolar ratio) and then incubated for 15 min either with 10 microM PGE2 (Cu/PGE2), 100 microM forskolin (Cu/forskolin), or 1 mM 8-bromoadenosine 3',5'-cyclic monophosphate (Cu/cAMP). Controls were incubated without Cu/histidine or with Cu/histidine alone. Basal release of LH-RH was 4.6 +/- 0.45 pg/15 min per MEA (mean +/- SEM). Net stimulated release during the 15-min exposure to PGE2, forskolin, or 8-bromoadenosine 3',5'-cyclic monophosphate was 3.6 +/- 0.52, 3.1 +/- 0.39, and 1.6 +/- 0.42 pg/15 min per MEA, respectively. Net stimulated release after exposure to Cu/PGE2, Cu/forskolin, or Cu/cAMP was 12.7 +/- 2.2, 9.9 +/- 1.46, and 1.4 +/- 1.9 pg/15 min per MEA, respectively, indicating that copper amplifies the action of PGE2 and forskolin but not cAMP action. When MEA were exposed to a mixture of PGE2 and forskolin for 15 min, the effects of these two secretagogues on LH-RH release were not additive, regardless of whether the MEA were pretreated with Cu/histidine. In contrast to PGE2 and forskolin, copper did not amplify K+ stimulation of LH-RH release and, moreover, when Cu/histidine-treated MEA were exposed to a mixture of PGE2 and 30 mM K+, the effects of these two secretagogues were additive. These results are supportive of the proposition that PGE2 stimulation of LH-RH release is mediated by the Ca-cAMP pathway and that copper amplification of PGE2 action is a postreceptor event.

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Selected References

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