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


METHODS
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.
University of Strathclyde, Department of Immunology, Glasgow, Scotland.
V A
VA
Ferro
W H
WH
Stimson
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000097:blood; D004971:Estrus / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000276:immunology / Q000494:pharmacology*; D037201:Follicle Stimulating Hormone, beta Subunit; D007114:Immunization; D007118:Immunoassay; D018796:Immunoconjugates / Q000276:immunology / Q000494:pharmacology; D008297:Male; D009500:Neutralization Tests; D009842:Oligopeptides / Q000276:immunology / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011962:Receptors, FSH / Q000187:drug effects / Q000378:metabolism; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism; D013745:Tetanus Toxoid / Q000276:immunology / Q000494:pharmacology
D037201:Follicle Stimulating Hormone, beta Subunit; D018796:Immunoconjugates; D009842:Oligopeptides; D010446:Peptide Fragments; D011962:Receptors, FSH; D013745:Tetanus Toxoid; D004958:Estradiol; D005640:Follicle Stimulating Hormone