Immunological hormone atrophy by gonadotropin-based drug

Luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin A (LHRH-PE40) and sequence-modified LHRH-PE40 (mLHRH-PE40) are two anti-tumour drugs developed by fusing either native or modified LHRH with the same PE40. This study was designed to evaluate their toxicity on the male genital tract. Male rats were treated intravenously or intraperitoneally with either LHRH-PE40 or mLHRH-PE40 on alternate days for 12 weeks. Serum and testes were examined to detect anti-LHRH, anti-LHRH-PE40 or anti-mLHRH-PE40 using an ELISA assay, testosterone level was measured by radioimmunoassay, and testicular morphology was evaluated. Rats receiving LHRH-PE40 intraperitoneal injections had higher anti-LHRH antibody titres, lower serum testosterone concentration and remarkable testicular atrophy, whereas those administrated with intravenous injections of either LHRH-PE40 or mLHRH-PE40 demonstrated no such changes. We concluded that the testicular atrophy can be attributed to higher titre of anti-LHRH antibodies, which was affected by both drug delivery and the LHRH motif of the chimeric protein.