In the present investigation, 17ß-estradiol (E2) and tamoxifen, an antiestrogen, were evaluated for their effects on the release of ascorbic acid (AA) and luteinizing hormone-releasing hormone (LHRH). Medial basal hypothalami (MBH) from adult male rats were incubated with graded concentrations of E2 (10-9 to 10-6 M) or a combination of E2 (10-7 M) and tamoxifen (10-7 and 10-6 M) in 0.5 ml of Krebs Ringer bicarbonate buffer for 1 hr. AA and LHRH in the incubation medium were measured by high-performance liquid chromatography and radioimmunoassay, respectively. E2 significantly elevated both AA and LHRH release and the minimal effective dose was 10-7 M. A combination of E2 (10-7 M) and tamoxifen (10-6 M) totally blocked E2-induced AA and LHRH release. The stimulatory effect of E2 was also suppressed in the presence of NG-monomethyl-l-arginine, a competitive inhibitor of nitric oxide synthase (NOS), illustrating that the release is mediated by nitric oxide (NO). To further characterize the role of NO, the tissues were incubated with E2 or a combination of E2 + (6 anllino-5, 8-quinolinedione) LY 83583 (10-6 and 10-5 M), an inhibitor of NOS. LY 83583 was effective in suppressing E2-induced AA and LHRH release, demonstrating that the effect was mediated by cyclic GMP. Incubation of the tissues with E2 or a combination of E2 + 1H-[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one (O.D.Q.) (10-5 and 10-4 M), a specific inhibitor of soluble guanylyl cyclase failed to alter AA release but significantly suppressed LHRH release. The role of a prostaglandin synthesis blocker in E2-lnduced AA and LHRH release was tested by incubating the tissues with E2 or a combination of E2 + Indomethacin (1.8 × 10-7 or 1.8 × 10-6 M). Indomethacin produced a significant decrease in E2-induced AA and LHRH release, suggesting that the release process required prostaglandins as an intracellular mediator. In conclusion, E2 stimulated both AA and LHRH release and the effect was mediated by NO and prostaglandins.
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