International Journal of Zoology and Animal Biology (IZAB)

ISSN: 2639-216X

Research Article

“Proof of Concept” Rabbit Experiments Demonstrating GHR106 (hIgG4) as GnRH Antagonist

Authors: Lee G*

DOI: 10.23880/izab-16000371

Abstract

“Proof of Concept” (P-o-C) experiments in rabbits were conducted to demonstrate reversible suppressions of serum reproductive hormones (LH, testosterone or E2) upon a single injection of a humanized monoclonal antibody against human GnRH receptor, GHR106 (hIgG4). In the case of a male rabbit, a single subcutaneous injection of either 1 mg/kg or 3 mg/kg of the antibody was shown to reduce concurrently the serum LH and testosterone concentrations by 60 to 80% for a period of one week or longer. The reproductive hormone levels returned to the normal range after next two weeks. Similarly, the suppressions of LH and estradiol (E2) were also observed within two days upon a single injection of GHR106 (hIgG4) in the female. The E2 levels can decrease to 30-60% of the normal over a period of one week followed by full recovery of both hormones during the next 5-10 days. P-o-C experiments were expanded to a scale of more than 30 rabbits with identical protocols to those of a single rabbit, in addition to the comparisons with those of the negative control. Reversible suppressions of reproductive hormones were observed consistently with all rabbits in the antibody injection groups, and were shown to be statistically significant. The circulation half-life of GHR106 (hIgG4) in rabbits was estimated to be 4 ± 1 day. Therefore, the results of this study revealed that GHR106(hIgG4) can be used as antibody-based long- acting GnRH antagonist with similar biological actions to those of decapeptide GnRH antagonist such as Cetrorelix or Antide. The relatively long half-life of the antibody-based GnRH antagonist, however, may be more beneficial to the treatment of gynecological and fertility-related diseases which may be caused by modulations of human GnRH receptor in humans, and also in other animal species for fertility controls.

Keywords: GHR106 Monoclonal Antibody; GnRH Antagonist; Rabbit GnRH Receptor; Antibody-Based GnRH Antagonist

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