title: Evidence that a short-lived effect of copper leads to amplification of prostaglandin E2 stimulation of the release of gonadotropin-releasing hormone from median eminence explants.
abstract: We have previously shown that copper (Cu) amplifies prostaglandin E2 (PGE2) stimulation of LHRH release from explants of the median eminence area (MEA) incubated under in vitro conditions. In this study, we have carried out an extensive comparative study of the kinetics of the process of PGE2 stimulation and C alpha-amplified PGE2 (Cu/PGE2) stimulation of LHRH release. MEA explains obtained from adult male rats were incubated under in vitro conditions, and LHRH released into the medium was assayed by RIA. Kinetic parameters were established by varying the time of exposure of the MEA to Cu or PGE2 and the dose of Cu or PGE2. Cu action requires a minimal 5-min period of exposure of the MEA, is rapidly manifested (less than 5 min after transfer of Cu-free medium), and is reversible (half-life, 10-15 min). Cu amplification of PGE2 action is a saturable function of the concentration of both Cu and PGE2; half-saturation and saturation were achieved with 120 and 200 microM copper, respectively, and with 0.6 and 10 microM PGE2, respectively. A 5-min exposure of Cu-treated MEA to PGE2 has the following time course of PGE2 action: the maximal rate of LHRH release is attained within 5 min; release is maintained at the maximal rate for another 5 min and then declines. Importantly, this decline is not prevented by a longer (15-min) exposure of the MEA to PGE2, indicating desensitization to PGE2 action. When MEA treated with Cu (5 min) and PGE2 (15 min) is allowed to recover for 45 min in buffer, the tissue regains its responsiveness to PGE2. All of the kinetic parameters of the process induced by PGE2 alone are similar to those described above for Cu/PGE2, except that the magnitude of the maximal rate of PGE2-stimulated release is 4- to 6-fold lower and that release is maintained at this rate for about 45 min. We also examined the PG structure specificity for stimulation of LHRH release and found that PGD2 by itself or after Cu pretreatment is much less effective than PGE2 in stimulating LHRH release. In summary, Cu amplification of PGE2 stimulation of LHRH release from LHRH neuronal terminals (i.e. MEA explants) involves rapid activation of a short-lived component.(ABSTRACT TRUNCATED AT 400 WORDS)
mesh_terms: D000818:Animals; D003300:Copper / Q000494:pharmacology*; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D011457:Prostaglandins D; D011458:Prostaglandins E; D007987:Gonadotropin-Releasing Hormone; D003300:Copper; D015232:Dinoprostone; D015230:Prostaglandin D2