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The gonadotropin-releasing hormone (GnRH) agonist-induced initial rise of bioactive LH and testosterone can be blunted in a dose-dependent manner by GnRH antagonist in the non-human primate

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Summary

Gonadotropin-releasing hormone (GnRH) agonists induce a clinically undesirable, transitory but very pronounced initial rise of gonadotropin and gonadal steroid secretion. We investigated, in a non-human primate model, whether the initial stimulatory effects of GnRH agonists can be avoided by a short period of pretreatment and simultaneous treatment with a GnRH antagonist. Three groups of five adult male cynomolgus monkeys (Macaca fascicularis) received a single s.c. biodegradable implant loaded with the GnRH agonist, buserelin ([D-Ser(TBu)6-desGly-NH2]-GnRH), releasing approximately 50 μg buserelin daily. From 1 week before to 1 week after inception of administration of GnRH agonist, group 1 received the GnRH antagonist vehicle, and groups 2 and 3 were given s.c. injections of the GnRH antagonist Nal-Glu ([Ac-D-Nal(2)1,D-4-Cl-Phe2, D-Pal3, D-Arg5,D-Glu6(AA),D-Ala10]-GnRH) at a dose of 450 or 2250 μg/kg daily. In the absence of GnRH antagonist, the GnRH agonist induced a marked elevation of serum luteinizing hormone (LH) and testosterone lasting for 2 and 5 days, respectively. In group 2, Nal-Glu reduced basal hormone secretion and delayed the peak of GnRH-agonist-induced hormone secretion by 1 day. In group 3, the GnRH-agonist-induced rise of LH and testosterone was prevented in three animals and did not exceed baseline hormone levels in the other two animals. Areas under the LH and testosterone curves were significantly reduced in group 3 compared to group 1. After withdrawal of the GnRH antagonist, a second transient rise of hormone secretion was observed. Except for testosterone in group 2, this rise did not exceed the baseline range of hormone concentrations. The study demonstrates that high doses of GnRH antagonist can prevent the GnRH agonist-induced initial rise of LH and testosterone secretion, while after withdrawal of the GnRH antagonist a second rise of hormone secretion occurs, which is less pronounced than with GnRH agoniit alone.

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Author notes

  1. O. P. Sharma

    Present address: Department of Medicine, Division of Endocrinology and Metabolism, University of Virginia Health, Sciences Center, Box 202, 22908, Charlottesville, VA, USA

Authors and Affiliations

  1. Institute for Reproductive Medicine, University of Münster, Münster, FRG

    O. P. Sharma, G. F. Weinbauer, H. M. Behre & E. Nieschlag

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  1. O. P. Sharma
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  2. G. F. Weinbauer
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  3. H. M. Behre
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  4. E. Nieschlag
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Supported by the Deutsche Forschungsgemeinschaft, grant DFG Ni 130/11-A1

Recipient of an Alexander von Humboldt Research Fellowship

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Sharma, O.P., Weinbauer, G.F., Behre, H.M. et al. The gonadotropin-releasing hormone (GnRH) agonist-induced initial rise of bioactive LH and testosterone can be blunted in a dose-dependent manner by GnRH antagonist in the non-human primate. Urol. Res. 20, 317–321 (1992). https://doi.org/10.1007/BF00922743

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