Abstract
PROBLEM: Hormone immunoneutralization is hampered by immunologic cross-reactivity caused by close-sequence homology between related molecules. One solution is to use smaller fragments to induce antibodies of greater specificity.
METHOD OF STUDY: A number of peptides selected from beta-follicle-stimulating hormone (FSH) were conjugated to tetanus toxoid and were used to immunize female rats. The antisera were examined for FSH cross-reactivity by immunoassays and in an in vitro bioassay.
RESULTS: In the immunoassays, the antisera did not react with FSH but did react with their respective peptides. In the bioassay, sera from VYKDPARPC- and CDSLYTYP-immunized animals inhibited FSH-receptor interaction by 73% and 68%, respectively. These animals also showed reduced estradiol levels. Sequences were synthesized around VYKDPARPC and were tested on a FSH-receptor-bearing Chinese hamster ovary cell line. LVYKDPARPC, VYKDPARPC, YKDPARPIC, CLVYKDPARP, and LVYKDPARP inhibited FSH-receptor interaction by greater than 50%. In female mice, TRDLVYKDPARPKI and LVYKDPARP disrupted estrous cycling in all animals; LVYKDPARPC and CLVYKDPARP disrupted cycling in three of five animals, whereas VYKDPARPC disrupted cycling in one of four animals.
CONCLUSIONS: Peptides from two areas of beta-FSH (VYKDPARP and DSLYTYP) were shown to raise FSH-neutralizing antibodies, which were able to suppress estradiol levels. An additional leucine residue to VYKDPARP greatly enhanced the peptide's ability to inhibit FSH-receptor binding and caused fertility disruption in vivo.
Original language | English |
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Pages (from-to) | 187-197 |
Number of pages | 11 |
Journal | American Journal of Reproductive Immunology |
Volume | 40 |
Issue number | 3 |
DOIs | |
Publication status | Published - 30 Sep 1998 |
Keywords
- amino acid sequence
- animal
- CHO cells
- cricetinae
- cross reactions
- enzyme-linked immunosorbent assay
- estradiol
- estrus
- female
- fertility
- follicle stimulating hormone
- beta Subunit
- immunization
- immunoassay
- Immunoconjugates
- male
- neutralization tests
- oligopeptides
- peptide fragments
- rats
- rats, sprague-dawley
- receptors, FSH
- sertoli cells
- tetanus toxoid