Suppression of Plasma Gonadotropins and Testosterone in Adult Male Monke( Macaca fascicularis ) by a Potent Inhibitory Analog of Gonadotropin-Releasing Hormone*

Publisher Website
Google Scholar
Abstract
The reduction of circulating levels of gonadotropins and testosterone is of value for the treatment of steroiddependent neoplasms and the control of fertility. We tested the ability of single and multiple doses of the GnRH antagonist [NAc- 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 μg/kg BW were given to castrate and intact animals. In Exp II, daily injections of antagonist at doses of 0, 50, 100, or 250 μg/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 I, a single injection of 5 μg/kg BW or more of GnRH-Ant to castrate animals significantly reduced plasma LH and FSH by 4 h after injection (P ≤ 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 μg/kg BW, and these hormones remained significantly lower than preinjection values over at least 48 h (P ≤ 0.05). A single injection of 50 ng/ kg B W or more of antagonist to intact animals markedly reduced plasma LH and testosterone by 6 h after administration (P ≤ 0.05), while 250 or 500 jtg/kg BW antagonist maintained LH and testosterone levels below 30% (P ≤ 0.05) of preinjection values for 24 h. In Exp II, daily injections of 250 μg/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 μg/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 atherapeutic agent in clinical situations requiring long term suppression of testicular function, such as fertility control, the treatment of steroid-dependent neoplasms, and precocious puberty.

This publication has 0 references indexed in Scilit: