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.
| Language | English |
|---|---|
| Pages | 187-197 |
| Number of pages | 11 |
| Journal | American Journal of Reproductive Immunology |
| Volume | 40 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 30 Sep 1998 |
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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
Cite this
}
Fertility-disrupting potential of synthetic peptides derived from the beta-subunit of follicle-stimulating hormone. / Ferro, Valerie A.; Stimson, William H.
In: American Journal of Reproductive Immunology, Vol. 40, No. 3, 30.09.1998, p. 187-197.Research output: Contribution to journal › Article
TY - JOUR
T1 - Fertility-disrupting potential of synthetic peptides derived from the beta-subunit of follicle-stimulating hormone
AU - Ferro, Valerie A.
AU - Stimson, William H.
PY - 1998/9/30
Y1 - 1998/9/30
N2 - 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.
AB - 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.
KW - amino acid sequence
KW - animal
KW - CHO cells
KW - cricetinae
KW - cross reactions
KW - enzyme-linked immunosorbent assay
KW - estradiol
KW - estrus
KW - female
KW - fertility
KW - follicle stimulating hormone
KW - beta Subunit
KW - immunization
KW - immunoassay
KW - Immunoconjugates
KW - male
KW - neutralization tests
KW - oligopeptides
KW - peptide fragments
KW - rats
KW - rats, sprague-dawley
KW - receptors, FSH
KW - sertoli cells
KW - tetanus toxoid
UR - http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1600-0897
U2 - 10.1111/j.1600-0897.1998.tb00412.x
DO - 10.1111/j.1600-0897.1998.tb00412.x
M3 - Article
VL - 40
SP - 187
EP - 197
JO - American Journal of Reproductive Immunology
T2 - American Journal of Reproductive Immunology
JF - American Journal of Reproductive Immunology
SN - 1046-7408
IS - 3
ER -