Gonadotrophin-releasing hormone (GnRH) overcomes GnRH antagonist-induced suppression of LH secretion in primates.
If the suppressive effects of gonadotrophin-releasing hormone (GnRH) antagonists on gonadotrophin secretion are mediated through GnRH-receptor occupancy alone, it should be possible to restore serum gonadotrophin levels by displacing the antagonist with exogenous GnRH. To test this hypothesis, eight adult crab-eating macaques (Macaca fascicularis), weight 4.7-7.6 kg, were subjected to the following treatment regimens. A GnRH-stimulation test was performed before and 4, 12 and 24 h after a single s.c. injection of the GnRH antagonist (N-Ac-D-p-Cl-Phe1,2, D-Trp3, D-Arg6, D-Ala10)-GnRH (ORG 30276). The stimulation tests were performed with 0.5, 5.0 or 50 micrograms GnRH given as a single i.v. bolus. Blood was taken before and 15, 30 and 60 min after each bolus for analysis of bioactive LH and testosterone. The GnRH-challenging doses were given as follows: 0.5 microgram GnRH was injected at 0 and 4 h, followed by 5.0 micrograms after 12 h and 50 micrograms after 24 h. One week later, 5.0 micrograms GnRH were given at 0 and 4 h, followed by 50 micrograms after 12 h and 0.5 microgram after 24 h. Finally, after another week, the GnRH challenges began with 50 micrograms at 0 and 4 h, followed by 0.5 microgram at 12 h and 5.0 micrograms at 24 h. This design permitted comparison of the LH and testosterone responses with respect to the dose of GnRH and the time after administration of GnRH antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008252:Macaca fascicularis; D010902:Pituitary Gland / Q000378:metabolism*; D010906:Pituitary Hormone-Releasing Hormones / Q000494:pharmacology*; D013739:Testosterone / Q000097:blood
D010906:Pituitary Hormone-Releasing Hormones; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C042691:LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-; D007986:Luteinizing Hormone