Structural requirements for the induction of "immunological castration" by linear monomeric LHRH-lys-MDP administered in saline.
It was previously shown that "castration" could be obtained in male mice by immunizing them in saline with a conjugate referred to as LHRH-Lys-MDP and containing the decapeptide hypothalamic hormone LHRH covalently linked to the adjuvant glycopeptide MDP-Lys. Since coupling was made using carbodiimide, it could have produced oligomers or isomers as well as monomers. In the present investigation male and female mice were immunized in saline with a linear monomeric MDP linked LHRH molecule obtained by total synthesis. Histological studies showed gonadal alterations in both male and female mice. The study of analogs provided a correlation between the "castrative" activity of LHRH-Lys-MDP and its chemical and antigenic structures. However, because LHRH antibody levels were not very high, mechanisms other than antibody response are discussed. Such totally synthesized molecules including a safe adjuvant could make a clinical use of LHRH immunization possible in endocrine-dependent cancers.
Hosmalin
A
A
CNRS UA-579, Immunothérapie Expérimentale, Institut Pasteur, Paris, France.
Carelli
C
C
Gaillard
J
J
Lefrancier
P
P
Drobecq
H
H
Leclerc
C
C
Amar
O
O
Audibert
F
F
Chedid
L
L
D000119:Acetylmuramyl-Alanyl-Isoglutamine; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000276:immunology*; D007114:Immunization; D007248:Infertility, Male / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012965:Sodium Chloride; D013737:Testis / Q000033:anatomy & histology
D000277:Adjuvants, Pharmaceutic; D007987:Gonadotropin-Releasing Hormone; D012965:Sodium Chloride; D000119:Acetylmuramyl-Alanyl-Isoglutamine