Immunization of male mice with luteinizing hormone-releasing hormone fusion proteins reduces testicular and accessory sex gland function.
Genes for ovalbumin-luteinizing hormone-releasing hormone 7 (LHRH-7) and thioredoxin-LHRH-7 fusion proteins (containing seven LHRH inserts) were constructed by cassette and mismatch mutagenesis and expressed in Escherichia coli. In experiment 1, 10 microgram of either ovalbumin-LHRH-7 or thioredoxin-LHRH-7 were suspended in Z-max adjuvant and injected three times at 4-wk intervals into postpubertal male BALB/c mice. In experiment 2, the fusion proteins were suspended in Immumax adjuvant and administered in equimolar quantities (0.4 nmol per injection) to postpubertal male BALB/c mice. In addition to injection of these two proteins alone, the proteins were also administered in different sequences or together in a mixture. Both LHRH fusion proteins induced significant antibody titers, which resulted in a significant decrease in vesicular gland and anterior prostate weight (measure of biological response) in both experiments. Vesicular gland and anterior prostate weight and LHRH antibody titers were significantly correlated in experiments 1 (r = -0.64) and 2 (r = -0.53). Percentage of animals responding to treatment varied from 40-60% in experiment 1 and from 11-89% in experiment 2, with the highest responses in treatments that used a combination of both fusion proteins. The variation in responders and nonresponders was evaluated by estimating antibody K(D) from displacement curves. Part, but not all, of the high antibody nonresponders can be explained by antibody affinity.
Quesnell
M M
MM
Department of Animal Sciences, Washington State University, Pullman, Washington 99164-6310, USA.
Zhang
Y
Y
de Avila
D M
DM
Bertrand
K P
KP
Reeves
J J
JJ
D000818:Animals; D001483:Base Sequence; D004822:Epididymis / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D007114:Immunization; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D011467:Prostate / Q000033:anatomy & histology / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D013879:Thioredoxins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
D011993:Recombinant Fusion Proteins; D007987:Gonadotropin-Releasing Hormone; D013879:Thioredoxins; D010047:Ovalbumin