17beta-estradiol stimulates ascorbic acid and LHRH release from the medial basal hypothalamus in adult male rats.
In the present investigation, 17beta-estradiol (E(2)) 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 E(2) (10 (-9) to 10(-6) M) or a combination of E(2) (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. E(2) significantly elevated both AA and LHRH release and the minimal effective dose was 10(-7) M. A combination of E(2) (10(-7) M) and tamoxifen (10(-6) M) totally blocked E(2)-induced AA and LHRH release. The stimulatory effect of E(2) was also suppressed in the presence of N(G)-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 E(2) or a combination of E(2) + (6 anilino-5, 8-quinolinedione) LY 83583 (10(-6) and 10(-5) M), an inhibitor of NOS. LY 83583 was effective in suppressing E(2)-induced AA and LHRH release, demonstrating that the effect was mediated by cyclic GMP. Incubation of the tissues with E(2) or a combination of E(2) + 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 E(2)-induced AA and LHRH release was tested by incubating the tissues with E(2) or a combination of E(2) + indomethacin (1.8 x 10 (-7) or 1.8 x 10(-6) M). Indomethacin produced a significant decrease in E(2)-induced AA and LHRH release, suggesting that the release process required prostaglandins as an intracellular mediator. In conclusion, E(2) stimulated both AA and LHRH release and the effect was mediated by NO and prostaglandins.
Karanth
Sharada
S
Pennington Biomedical Research Center (Louisiana State University), Baton Rouge, Louisiana 70808-4124, USA. skaranth@cox.net
Yu
Wen H
WH
Mastronardi
Claudio M
CM
McCann
Samuel M
SM
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D006152:Cyclic GMP / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007033:Hypothalamus, Middle / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology
D000634:Aminoquinolines; D011453:Prostaglandins; D013629:Tamoxifen; D009569:Nitric Oxide; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; C041715:6-anilino-5,8-quinolinedione; D006152:Cyclic GMP; D001205:Ascorbic Acid; D007213:Indomethacin