Effect of a GnRH vaccine formulation on testosterone concentrations and reproduction in adult male rats

Abstract

In this study is described the effect of different doses of the gonadotropin releasing hormone (GnRH) mimetic peptide GnRHm1-TT, administered in three immunization schemes to define the most effective alternative combination for the treatment of prostate cancer. The design elements of the peptide immunogens are the GnRH-m1 linked to a T helper epitope of tetanus toxoid (TT) by chemical synthesis. Three doses of peptide GnRHm1-TT: 125, 300 and 750 µg were formulated in oil-based emulsions and tested in Copenhagen rats. Three immunization schemes (weekly, fortnightly and monthly) were used. As a result, the 750 µg dose generated a specific anti-GnRH antibody response in the fortnightly and monthly schemes, in contrast to 125 µg and 300 µg doses. The anti-GnRH seroconversion in the best responders corresponded with a decline, both in the testosterone levels down to castration and the size and weight of reproductive organs, an effect absent for the remaining doses of the three immunization schemes. The best variant corresponded to the 750 µg dose in a monthly regime. These findings demonstrated a marked immune-neutralization of the GnRH hormone for a subsequent immunological castration.

Keywords

• cancer vaccine
• GnRH
• rats
• castration
• testosterone