Immunization against exon 1 decapeptides from the lutropin/choriogonadotropin receptor or the follitropin receptor as potential male contraceptive.
Pituitary gonadotropin hormones lutropin (LH) and follitropin (FSH) control steroidogenesis and gametogenesis in male and female gonads through interaction with G protein-coupled receptors, LHR and FSHR. In the male, LH acts on leydig cells and is mostly responsible for the acquisition of puberty and the production of androgens while FSH, together with androgens, regulates spermatogenesis within Sertoli cells. We have engineered filamentous phages displaying mouse LHR and human FSHR decapeptides chosen in hormone binding regions. Peptides from both receptors displayed on phages belong either to the receptor specific exon 1 (amino acids 18-27) or to the homologous exon 4 (amino acids 98-107). Vaccination of prepubertal BALB/c male mice with hybrid phages using sub-cutaneous or intraperitoneal injections induced immunity against receptors. Anti-receptor immunization produced agonist or antagonist effects depending only on the circulating levels of the antibodies. Both anti-LHR and anti-FSHR vaccines induced efficient as well as reversible male contraception, through different mechanisms: targeting LH receptors inhibited or hyperstimulated Leydig cell testosterone production while targeting FSH receptors did not affect testosterone levels.
Remy
J J
JJ
Unité Récepteurs et Communications Cellulaires, INRA Biotechnologies, Jouy-en-Josas, France.
Couture
L
L
Rabesona
H
H
Haertle
T
T
Salesse
R
R
D000595:Amino Acid Sequence; D000818:Animals; D006063:Chorionic Gonadotropin / Q000276:immunology* / Q000378:metabolism*; D003272:Contraceptive Agents, Male / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D005091:Exons / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage / Q000276:immunology*; D011962:Receptors, FSH / Q000276:immunology*; D011974:Receptors, LH / Q000276:immunology*; D013739:Testosterone / Q000097:blood; D013963:Thyroid Hormones / Q000097:blood; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology
D006063:Chorionic Gonadotropin; D003272:Contraceptive Agents, Male; D007106:Immune Sera; D009842:Oligopeptides; D011962:Receptors, FSH; D011974:Receptors, LH; D013963:Thyroid Hormones; D014614:Vaccines, Synthetic; D013739:Testosterone