| Summary: | 碩士 === 國立陽明大學 === 生物化學研究所 === 90 === Gonadotropin-releasing hormone GnRH, an endogenous hormone that contains 10 amino acid residues, functions as a key hormone in the regulation of the pituitary-gonadal axis. The expression of GnRH or its receptor is increased in several human malignancies, including cancers of breast, ovary, endometrium, and prostate. Previous studies showed that immunization of the antigen containing the Pseudomonas exotoxin receptor胕inding domain and 12 copies of GnRH (PE1a-GnRH12) resulted in the generation of high titer antibodies specific for GnRH. In addition, anti-GnRH antibodies effectively neutralized GnRH activity in vivo, as demonstrated by the degeneration of the ovaries in the injected rabbits. In this study, we have constructed an anti-GnRH DNA vaccine which contains Murine Ig k-chain V-J2-C signal peptide sequence in front of PE1a-GnRH19. Our preliminary study showed that PE1a-GnRH19 was synthesized and released into the medium after cell transfected with anti-GnRH DNA vaccine. In animal study, we observe that induction of high-titer anti-GnRH antibodies in mice by immunization of anti-GnRH DNA vaccine results in the sterilization of mice. Thus, the immunogen PEIa-GnRH19 may be applied for nonsurgical contraception in cats and dogs. Because anti-GnRH antibody could be functionally analogous to GnRH antagonist, which has been used to treat patients with ovarian cancer, thus, the induction of an immune response to GnRH by anti-GnRH DNA vaccine presents a potential therapeutic application for the treatment of GnRH-sensitive ovarian cancer.
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