In vitro inhibition of the biological activity of follicle-stimulating hormone by anti-peptide antisera representing the human follicle-stimulating hormone beta subunit sequence 33-53.
There are few male contraceptive methods, and research is required to broaden the scope of available male antifertility methods. Two approaches toward hormonal contraception are currently being investigated. The first relies on elimination of testosterone while the second is based upon immunizations against FSH. However, most anti-whole FSH antisera cross-react with LH, thereby possibly inhibiting testosterone and leading to potential loss of libido. Therefore, a more effective alternative would be to define an FSH peptide that differs significantly from LH in order to prevent cross-reactivity between anti-FSH antisera and LH. Two peptides were selected from the beta subunit of FSH that were considered to be inducers of anti-FSH activity but not anti-LH activity. The first peptide (sequence beta33-53) is a linear antigenic site of human FSH found only in anti-FSH antisera that do not cross-react with LH. The second peptide (sequence beta81-95) is a part of FSH that confers receptor specificity. These peptides, in monomer and tandem form, were used to immunize rabbits. The antisera were tested for inhibition of FSH activity in a bioassay; they were also tested in a Leydig cell assay to detect anti-LH activity. It was found that antisera raised against the beta33-53 tandem could inhibit the FSH bioactivity but not that of LH. Antisera against the beta33-53 monomer or the beta81-95 monomer or tandem did not inhibit FSH. Thus, the tandem peptide beta33-53 is an attractive candidate for use as antigen in a male contraceptive vaccine. The better results obtained with tandem vaccinations might be related to the ability of the tandem peptide to direct the antibody response toward the N-terminal end of the peptide and to raise antisera with the ability to react with shorter chains of amino acids.
Westhoff
W E
WE
Institute for Animal Science and Health, Department of Molecular Recognition, Lelystad, The Netherlands.
Slootstra
J W
JW
Puijk
W C
WC
van Leeuwen
L
L
Schaaper
W M
WM
Oonk
H B
HB
Meloen
R H
RH
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D000941:Antigens / Q000276:immunology; D002460:Cell Line; D003269:Contraception, Immunologic; D000242:Cyclic AMP / Q000096:biosynthesis; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007106:Immune Sera / Q000276:immunology / Q000494:pharmacology*; D007114:Immunization; D007985:Leydig Cells / Q000187:drug effects; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D011817:Rabbits
D000941:Antigens; D007106:Immune Sera; D010446:Peptide Fragments; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP