Summary
The feasibility of using a vaccine against luteinizing-hormone-releasing factor for supression of pituitary and gonadal functions has been indicated for some time. Antibody production against this low-molecular-weight, naturally occurring decapeptide, however, requires to be coupled to a carrier protein to enhance its immunogenicity. LHRH was coupled to diphtheria toxoid (DT). Adult male Sprague-Dawley rats with a mean basal body weight of 200g were immunized with anti-LHRH-DT (20 μg/injection/rat) at four-week intervals. An equal number of unexposed animals served as controls. Six animals were killed every two weeks up the end of the week 43. The vaccination schedule did not have any effect on the gain in body weight, nor was any adverse effect of vaccination observed in the course of the investigations. The pituitary, prostate, epididymis, testes, seminal vesicles, adrenal and thyroid were excised for determination of organ weight and histological examination. The adrenal, pituitary and thyroid showed no remarkable weight changes during the observation period, whereas the weights of the reproductive organs demonstrated significant reductions compared to those of the control group. The histopathology revealed marked to significant changes in the gonads and the accessory sex organs including the prostate. A progressive phase of regeneration of spermatogenesis was evident 98 days after vaccination. Total recovery of spermatogenesis was observed 300 days after vaccination. The mating studies showed the return of fertility 300 days after vaccination. The litters borne were normal. Prostate showed recovery after 154 days of vaccination. Our observations lend strong support to the hypothesis that anti-LHRH vaccine can be effectively used on the management of prostate carcinoma. If the vaccination is given together with a suitable dose of long-acting androgen, contained in an adequate delivery system, the regimen may be used for the regulation of male fertility.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arimura A, Sato H, Kumasaka T., Woborek RB, Debeljuk L, Dunn J, Schally AV (1973) Production of antiserum of LH-releasing hormone (LHRH) associated with gonadal atrophy in rabbits; development of radioimmunoassay for LHRH. Endocrinology 934:1092
Arimura A, Shino M, Delacruz KG, Rennels EG, Schally AV (1976) Effect of active and passive immunization with luteinizing hormone-releasing hormone on serum luteinizing hormone and follicle-stimulating hormone levels and the ultra-structure of the pituitary gonadotropins in castrated male rats. Endocrinology 99:291
Catt KJ, Ketelslegers JM, Dufau ML (1976) Receptors for gonadotropic hormones. In: Blecher M (ed) Methods in receptor research, vol 1. Dekker, New York, p 175
Chappel SC, Ellinwood WE, Huckins AC, Herbert DC, Spies HG (1980) Active immunization of male rhesus monkeys against luteinizing hormone-releasing hormone. Biol Reprod 22:322
Clayton RN, Catt KJ (1987) Gonadotropin-releasing hormone receptors: characterization, physiological regulation and relationship to reproductive function. Endocrinol Rev 2:186
Corbin A, Bex FJ (1987) Animal pharmacology and safety studies with an LHRH agonist. J Androl 8:5
Giri DK, Chaudhuri R, Jayashankar R, Neelaram GS, Jayaraman S, Talwar GP (1990) Histopathological changes in reproductive organs of male Wistar rats following active immunization against LHRH. Exp Mol Pathol 52:54
Hsueh AJW, Jones PBC (1987) Extrapituitary action of gonadotropin-releasing hormone. Endocr Rev 2:437
Jayashankar R, Chandhuri MK, Singh O, Alan A, Talwar GP (1989) Semisynthetic anti-LHRH vaccine causing atrophy of the prostate. Prostate 14:3
Labrie F, Belanger A, Cusan L, Seguin C, Pelletier G, Kelly PA, Reeves JJ, Lefebvre FA, Lemay A, Gourdeu Y, Raynaud JP (1980) Antifertility effects of LHRH agonists in the male. J Androl 7:209
Ladd A, Prahbu Y, Tsong Y, Probst T, Thau RB (1988) Active immunization against gonadotropin-releasing hormone combined with androgen supplementation is a promising antifertility vaccine for males. Am J Reprod Immunol Microbiol 17:121
Lefebrve FA, Pelletier BG, Labrie F (1984) Recovery of gonadal functions in the adult male rat following cessation of five-month daily treatment with an LHRH agonist. J Androl 5:181
Nieschlag E, Behre HE, Weinbauer GH (1989) Hormonal methods for the regulation of male fertility. In: Serio M (ed) Perspectives in andrology. Raven Press, New York, p 517
Orlowski J, Bird CE, Clark AF (1983) Androgen 5 α-reductase and 3 α-hydroxy steroid dehydrogenase activities in ventral prostate epithelial and stromal cells from immature and mature rats. J Endocrinol 99:131
Popkin RM, Fraser HM (1985) Changes in pituitary and ovarian LHRH-receptors after active immunization of female rats against LH or LHRH. J Reprod Fertil 73:491
Rovan E, Weinbauer GF, Frick J, Adam H (1983) Ultrastructural analysis of rat testis after gossypol acetic acid (GAA) treatment. Urol Res 11:556
Rovan E, Fiebiger E, Hacker G, Kalla NR, Talwar GP, Frick J (1991) Effect of anti-LHRH vaccine on serum testosterone and pituitary gonadotropins using immunocytochemical method. (in press)
Sheth AR, Joseph R, Maitra A (1987) In vitro effect of LHRH, TRH and inhibin on testosterone metabolism in rat ventral prostate. Indian Exp Biol 25:503
Talwar GP (1985) Immunology of gonadotropin-releasing hormone. J Steroid Biochem 27:548
Upadhyay SN, Alam A, Talwar GP (1989) Functional morphology of testis and its excurrent ducts in rats immunized with synthetic luteinizing hormone-releasing hormone conjugated to tetanus toxoid. J Reprod Immunol (Netherlands) 16:151
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rovan, E., Fiebiger, E., Kalla, N.R. et al. Effect of active immunization to luteinizing-hormone-releasing hormone on the fertility and histoarchitecture of the reproductive organs of male rat. Urol. Res. 20, 323–334 (1992). https://doi.org/10.1007/BF00922744
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00922744