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.

Original languageEnglish
Pages (from-to)187-197
Number of pages11
JournalAmerican Journal of Reproductive Immunology
Volume40
Issue number3
DOIs
Publication statusPublished - 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

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