Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Feb;87(3):901–903. doi: 10.1073/pnas.87.3.901

Suppression of meiosis of male germ cells by an antagonist of luteinizing hormone-releasing hormone.

B Szende 1, T W Redding 1, A V Schally 1
PMCID: PMC53376  PMID: 2405399

Abstract

Male nude mice were implanted with osmotic minipumps releasing 50 micrograms of a potent antagonist of luteinizing hormone-releasing hormone (LH-RH) per day [N-Ac-[D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH-RH] (SB-75) [Nal(2), 3-(2-naphthyl)alanine; Phe(pCl), 4-chlorophenylalanine; Pal(3), 3-(3-pyridyl)alanine; Cit, citrulline], or they were treated with s.c. injections of SB-75 (25 micrograms twice a day). Another group of nude mice received an injection of microcapsules of the agonist [D-Trp6]LH-RH liberating 25 micrograms/day. One month after the initiation of treatment, the testicular weights were significantly reduced and the blood testosterone values were at castration levels in all treated groups. Histologically, only the testicles of the mice treated with SB-75 released from minipumps showed a significant decrease of meiosis. The most advanced forms of germ cells were spermatogonia in 26%, spermatocytes in 17%, and round spermatids in 35% of the seminiferous tubules. Only 22% of the tubules contained elongated spermatids. The suppression of meiotic activity by this modern LH-RH antagonist can possibly be used for the development of methods for male contraception and for the protection of germ cells against the damage caused by cytotoxic drugs and x-radiation.

Full text

PDF
901

Images in this article

903Image
on p.903

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bajusz S., Csernus V. J., Janaky T., Bokser L., Fekete M., Schally A. V. New antagonists of LHRH. II. Inhibition and potentiation of LHRH by closely related analogues. Int J Pept Protein Res. 1988 Dec;32(6):425–435. doi: 10.1111/j.1399-3011.1988.tb01373.x. [DOI] [PubMed] [Google Scholar]
  2. Bint Akhtar F., Weinbauer G. F., Nieschlag E. Acute and chronic effects of a gonadotrophin-releasing hormone antagonist on pituitary and testicular function in monkeys. J Endocrinol. 1985 Mar;104(3):345–354. doi: 10.1677/joe.0.1040345. [DOI] [PubMed] [Google Scholar]
  3. Debeljuk L., Maines V. M., Coy D. H., Schally A. V. Effect of a powerful antagonist of LH-RH on testicular function in prepubertal male rats. Arch Androl. 1983 Aug;11(1):89–93. doi: 10.3109/01485018308987466. [DOI] [PubMed] [Google Scholar]
  4. Debeljuk L., Schally A. V. Antifertility effects of a potent LH-RH antagonist in male and female rats. Int J Fertil. 1986 Sep-Oct;31(4):284–292. [PubMed] [Google Scholar]
  5. Karashima T., Zalatnai A., Schally A. V. Protective effects of analogs of luteinizing hormone-releasing hormone against chemotherapy-induced testicular damage in rats. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2329–2333. doi: 10.1073/pnas.85.7.2329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lewis R. W., Dowling K. J., Schally A. V. D-Tryptophan-6 analog of luteinizing hormone-releasing hormone as a protective agent against testicular damage caused by cyclophosphamide in baboons. Proc Natl Acad Sci U S A. 1985 May;82(9):2975–2979. doi: 10.1073/pnas.82.9.2975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Pelletier G., Cusan L., Auclair C., Kelly P. A., Désy L., Labrie F. Inhibition of spermatogenesis in the rat by treatment with [D-Ala6, Des-Gly-NH210] LHRH ethylamide. Endocrinology. 1978 Aug;103(2):641–643. doi: 10.1210/endo-103-2-641. [DOI] [PubMed] [Google Scholar]
  8. Rivier C., Rivier J., Vale W. Antireproductive effects of a potent gonadotropin-releasing hormone antagonist in the male rat. Science. 1980 Oct 3;210(4465):93–95. doi: 10.1126/science.6774418. [DOI] [PubMed] [Google Scholar]
  9. Rivier C., Rivier J., Vale W. Effect of a potent GnRH antagonist and testosterone propionate on mating behavior and fertility in the male rat. Endocrinology. 1981 May;108(5):1998–2001. doi: 10.1210/endo-108-5-1998. [DOI] [PubMed] [Google Scholar]
  10. Schally A. V., Kook A. I., Monje E., Redding T. W., Paz-Bouza J. I. Combination of a long-acting delivery system for luteinizing hormone-releasing hormone agonist with Novantrone chemotherapy: increased efficacy in the rat prostate cancer model. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8764–8768. doi: 10.1073/pnas.83.22.8764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Schally A. V., Paz-Bouza J. I., Schlosser J. V., Karashima T., Debeljuk L., Gandle B., Sampson M. Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats. Proc Natl Acad Sci U S A. 1987 Feb;84(3):851–855. doi: 10.1073/pnas.84.3.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Vickery B. H. Comparison of the potential for therapeutic utilities with gonadotropin-releasing hormone agonists and antagonists. Endocr Rev. 1986 Feb;7(1):115–124. doi: 10.1210/edrv-7-1-115. [DOI] [PubMed] [Google Scholar]
  13. Weinbauer G. F., Göckeler E., Nieschlag E. Testosterone prevents complete suppression of spermatogenesis in the gonadotropin-releasing hormone antagonist-treated nonhuman primate (Macaca fascicularis). J Clin Endocrinol Metab. 1988 Aug;67(2):284–290. doi: 10.1210/jcem-67-2-284. [DOI] [PubMed] [Google Scholar]
  14. Weinbauer G. F., Surmann F. J., Akhtar F. B., Shah G. V., Vickery B. H., Nieschlag E. Reversible inhibition of testicular function by a gonadotropin hormone-releasing hormone antagonist in monkeys (Macaca fascicularis). Fertil Steril. 1984 Dec;42(6):906–914. doi: 10.1016/s0015-0282(16)48264-6. [DOI] [PubMed] [Google Scholar]
  15. da Cunha M. F., Meistrich M. L., Nader S. Absence of testicular protection by a gonadotropin-releasing hormone analogue against cyclophosphamide-induced testicular cytotoxicity in the mouse. Cancer Res. 1987 Feb 15;47(4):1093–1097. [PubMed] [Google Scholar]
  16. van Steenbrugge G. J., Ultee-van Gessel A. M., Groen M., de Jong F. H., Schroeder F. H. Administration of an LHRH-antagonist to male mice: effects on in vivo secretion of hormones and on the growth of a transplantable human prostatic carcinoma. Life Sci. 1987 Mar 30;40(13):1335–1343. doi: 10.1016/0024-3205(87)90591-1. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES