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dc.contributor.authorAdams, Lizabeth A.en_US
dc.contributor.authorSteiner, Robert A.en_US
dc.contributor.authorBremner, William J.en_US
dc.contributor.authorVickery, Brian H.en_US
dc.contributor.authorNestor, Jr., John J.en_US
dc.date.accessioned2008-10-17T20:43:18Z
dc.date.available2008-10-17T20:43:18Z
dc.date.issued1986-01en_US
dc.identifier.citationJ Clin Endocrinol Metab. 1986 Jan;62(1):58-63en_US
dc.identifier.urihttp://hdl.handle.net/1773/4467
dc.description.abstractThe reduction of circulating levels of gonadotropins and testosterone is of value for the treatment of steroid-dependent neoplasms and the control of fertility. We tested the ability of single and multiple doses of the GnRH antagonist [N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Ala10]GnRH (GnRH-Ant) to suppress levels of these hormones in intact and castrate adult male cynomolgus monkeys. In Exp I, single injections of the antagonist at doses of 0 (vehicle), 5, 50, 250, and 500 micrograms/kg BW were given to castrate and intact animals. In Exp II, daily injections of antagonist at doses of 0, 50, 100, or 250 micrograms/kg BW were given to intact animals for 21 days. Plasma levels of testosterone, FSH, and LH were determined by RIA, and in intact animals, LH levels were measured by bioassay. In Exp 1, a single injection of 5 micrograms/kg BW or more of GnRH-Ant to castrate animals significantly reduced plasma LH and FSH by 4 h after injection (P less than or equal to 0.01). Nadir levels (40% of preinjection control values) of LH and FSH were reached 8 and 24 h, respectively, after administration of 250 or 500 micrograms/kg BW, and these hormones remained significantly lower than preinjection values over at least 48 h (P less than or equal to 0.05). A single injection of 50 micrograms/kg BW or more of antagonist to intact animals markedly reduced plasma LH and testosterone by 6 h after administration (P less than or equal to 0.05), while 250 or 500 micrograms/kg BW antagonist maintained LH and testosterone levels below 30% (P less than or equal to 0.05) of preinjection values for 24 h. In Exp II, daily injections of 250 micrograms/kg BW antagonist to intact animals resulted in near-castrate levels of plasma testosterone which were achieved by 24 h after the first injection of antagonist and persisted for the ensuing 20 days. Daily injections of 100 micrograms/kg BW or less of antagonist were ineffective in suppressing testosterone. Thus, this potent GnRH antagonist acutely and chronically lowers gonadotropin and testosterone levels in adult male cynomolgus monkeys. By virtue of its inhibitory effect, this antagonist is potentially useful as a therapeutic agent in clinical situations requiring long term suppression of testicular function, such as fertility control, the treatment of steroid-dependent neoplasms, and precocious puberty.en_US
dc.language.isoen_USen_US
dc.publisherEndocrine Societyen_US
dc.subjectmale contraceptionen_US
dc.subjectandrologyen_US
dc.subject5-alpha reductase inhibitorsen_US
dc.subjectgonadotropinsen_US
dc.subjectklinefelter's syndromeen_US
dc.subjectspermatogenesisen_US
dc.subjectreifenstein's syndromeen_US
dc.subjecttestosteroneen_US
dc.subjectcolchicineen_US
dc.subject.meshMaleen_US
dc.subject.meshLuteinizing Hormone, blooden_US
dc.subject.meshSexual Maturationen_US
dc.subject.meshRadioimmunoassayen_US
dc.subject.meshKineticsen_US
dc.subject.meshComparative Studyen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshMacaca fascicularisen_US
dc.subject.meshTestosterone, blooden_US
dc.subject.meshOrchiectomyen_US
dc.subject.meshGonadorelin, analogs & derivatives, antagonists & inhibitors, pharmacologyen_US
dc.subject.meshFollicle Stimulating Hormone, blooden_US
dc.subject.meshAnimalsen_US
dc.subject.meshResearch Support, U.S. Gov't, P.H.S.en_US
dc.titleSuppression of plasma gonadotropins and testosterone in adult male monkeys (Macaca fascicularis) by a potent inhibitory analog of gonadotropin-releasing hormoneen_US
dc.typeArticleen_US


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