Structural requirements for the induction of "immunological castration" by linear monomeric LHRH-lys-MDP administered...

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.