Fertility-disrupting potential of synthetic peptides derived from the beta-subunit of follicle-stimulating hormone

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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.

LanguageEnglish
Pages187-197
Number of pages11
JournalAmerican Journal of Reproductive Immunology
Volume40
Issue number3
DOIs
Publication statusPublished - 30 Sep 1998

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Beta Subunit Follicle Stimulating Hormone
FSH Receptors
Follicle Stimulating Hormone
Fertility
Peptides
Immunoassay
Biological Assay
Immune Sera
Estradiol
Tetanus Toxoid
Antibody Specificity
Sequence Homology
Cricetulus
Neutralizing Antibodies
Leucine
Ovary
Hormones
Cell Line
Serum

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

@article{fc57e848cfd24dceb7035fa7e60c1c68,
title = "Fertility-disrupting potential of synthetic peptides derived from the beta-subunit of follicle-stimulating hormone",
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.",
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",
author = "Ferro, {Valerie A.} and Stimson, {William H.}",
year = "1998",
month = "9",
day = "30",
doi = "10.1111/j.1600-0897.1998.tb00412.x",
language = "English",
volume = "40",
pages = "187--197",
journal = "American Journal of Reproductive Immunology",
issn = "1046-7408",
number = "3",

}

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 -