Suppression of plasma gonadotropins and testosterone in adult male monkeys (Macaca fascicularis) by a potent inhibitory analog of gonadotropin-releasing hormone

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Suppression of plasma gonadotropins and testosterone in adult male monkeys (Macaca fascicularis) by a potent inhibitory analog of gonadotropin-releasing hormone

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dc.contributor.author Adams, Lizabeth A. en_US
dc.contributor.author Steiner, Robert A. en_US
dc.contributor.author Bremner, William J. en_US
dc.contributor.author Vickery, Brian H. en_US
dc.contributor.author Nestor, Jr., John J. en_US
dc.date.accessioned 2008-10-17T20:43:18Z
dc.date.available 2008-10-17T20:43:18Z
dc.date.issued 1986-01 en_US
dc.identifier.citation J Clin Endocrinol Metab. 1986 Jan;62(1):58-63 en_US
dc.identifier.uri http://hdl.handle.net/1773/4467
dc.description.abstract The 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.iso en_US en_US
dc.publisher Endocrine Society en_US
dc.subject male contraception en_US
dc.subject andrology en_US
dc.subject 5-alpha reductase inhibitors en_US
dc.subject gonadotropins en_US
dc.subject klinefelter's syndrome en_US
dc.subject spermatogenesis en_US
dc.subject reifenstein's syndrome en_US
dc.subject testosterone en_US
dc.subject colchicine en_US
dc.subject.mesh Male en_US
dc.subject.mesh Luteinizing Hormone, blood en_US
dc.subject.mesh Sexual Maturation en_US
dc.subject.mesh Radioimmunoassay en_US
dc.subject.mesh Kinetics en_US
dc.subject.mesh Comparative Study en_US
dc.subject.mesh Time Factors en_US
dc.subject.mesh Macaca fascicularis en_US
dc.subject.mesh Testosterone, blood en_US
dc.subject.mesh Orchiectomy en_US
dc.subject.mesh Gonadorelin, analogs & derivatives, antagonists & inhibitors, pharmacology en_US
dc.subject.mesh Follicle Stimulating Hormone, blood en_US
dc.subject.mesh Animals en_US
dc.subject.mesh Research Support, U.S. Gov't, P.H.S. en_US
dc.title Suppression of plasma gonadotropins and testosterone in adult male monkeys (Macaca fascicularis) by a potent inhibitory analog of gonadotropin-releasing hormone en_US
dc.type Article en_US


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