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Immunological Approaches to Contraception and Promotion of Fertility pp 125–141Cite as

LHRH Immunoneutralization: Basic Studies and Prospects for Practical Application

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Part of the book series: Reproductive Biology ((RBIO))

Abstract

The hypothalamic decepeptide, pG1u-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-G1y-NH2, luteinizing hormone releasing hormone (LHRH) or gonadotrophin releasing hormone, plays a central role in reproduction in all mammalian species. Our understanding of its physiological role has been guided on one hand by effects of administering LHRH at different doses and frequencies to humans or experimental animals who lack the hormone, and on the other by studying the consequences of desensitizing the pituitary by repeated exposure to agonist analogues, by blocking the LHRH receptors by chemical antagonists or by the neutralizing endogenous LHRH by antibodies (Fig. 1). These studies have shown that for continued stimulation, the pituitary gonadotroph must be exposed to small pulses of LHRH at a frequency of one per 60–120 min (1–3) which appear to the pattern of normal hypothalamic activity as reflected by the frequency of luteinizing hormone (LH) pulses from the pituitary gland and from what is known from measuring LHRH in the hypophysial portal blood (4).

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References

  1. E. Knobil, The neuroendocrine control of the menstrual cycle. Rec. Prog. Horm. Res. 36:53 (1980).

    PubMed  CAS  Google Scholar 

  2. J. Sandow, Clinical applications of LHRH and its analogues. Clin Endocrinol. 18:571 (1983).

    Article  CAS  Google Scholar 

  3. H.M. Fraser, New prospects for luteinising hormone releasing hormone as a contraceptive and therapeutic agent. Br. Med. J. 285:990 (1982).

    Article  CAS  Google Scholar 

  4. I.J. Clarke and J.T. Cummins, The temporal relationship between gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) secretion in ovariectomized ewes. Endocrinology 111:1737 (1982).

    Article  PubMed  CAS  Google Scholar 

  5. H.M. Fraser and A. Gunn, Effects of antibodies to luteinizing hormone releasing hormone in the male rabbit and on the rat oestrous cycle. Nature 244: 160 (1973).

    Article  PubMed  CAS  Google Scholar 

  6. Y. Koch, P. Chobsieng, U. Zor, M. Fridkin and H.R. Lindner, Suppression of gonadotrophin secretion and prevention of ovulation in the rat by antiserum to synthetic gonadotrophin-releasing hormone. Biochem biophys Res Commun 55:623 (1973).

    Article  PubMed  CAS  Google Scholar 

  7. A. Arimura, H. Sato, T. Kumasaka, R.B. Worobec, L. Deleljuk, J. Dunn and A.V. Schally, Production of antiserum to LH-releasing hormone (LH-RH) associated with gonadal atrophy in rabbits: development of radioimmunoassays for LH-RH. Endocrinology 93: 1092 (1973).

    Article  PubMed  CAS  Google Scholar 

  8. G.A. Lincoln and H.M. Fraser, Blockade of episodic secretion of luteinizing hormone in the ram by the administration of antibodies to luteinizing hormone releasing hormone. Biol. Reprod 21: 1239 (1979).

    Article  PubMed  CAS  Google Scholar 

  9. G.B. Ellis, C. Desjardins and H.M. Fraser, Control of pulsatile LH release in male rats. Neuroendocrinology 37: 177 (1983).

    Article  PubMed  CAS  Google Scholar 

  10. H.M. Fraser, ‘Effects of antibodies to luteinizing hormone releasing hormone on reproductive functions in rodents’, in: “Immunization with Hormones in Reproduction Research” E. Nieschlag, ed., North-Holland Publishing Company, Amsterdam (1975)

    Google Scholar 

  11. H.M. Fraser, A. Gunn, R. Borthwick and A.F. Fraser, Sterilising by immunization. Vet. Rec. 96: 323 (1975).

    Article  PubMed  CAS  Google Scholar 

  12. H.M. Fraser, Inhibition of reproductive function by antibodies to luteinizing hormone-releasing hormone, in: “Immunological aspects of reproduction and fertility control” J.P. Hearn, ed., MTP Press, Lancaster, U.K. (1980).

    Google Scholar 

  13. H.M. Fraser, R.M. Sharpe, G.A. Lincoln and A.J. Harmer, LHRH antibodies: Their use in the study of hypothalamic LHRH and testicular LHRH-like material, and possible contraceptive applications in: “Progress Towards a Male Contraceptive” S.L. Jeffcoate and M. Sandler eds., John Wiley & Sons Ltd. (1982).

    Google Scholar 

  14. H.M. Fraser, A.S. McNeilly and R.M. Popkin, Passive immunization against LHRH: elucidation of the role of LHRH in controlling LH and FSH secretion and LHRH receptors in: “Immunological Aspects of Reproduction in Mammals” B. Crighton ed., Butterworths (1984).

    Google Scholar 

  15. I.T. Huhtaniemi, J.M. Stewart, K. Channabasavaiah, H.M. Fraser and R.N. Clayton, Effect of treatment with GnRH antagonist, GnRH antiserum and bromocriptine on pituitary — testicular function of adult rats. Mol. Cell. Endocrinol 34:127 (1984).

    Article  PubMed  CAS  Google Scholar 

  16. H.M. Fraser, A. Gunn, S.L. Jeffcoate and D.T. Holland, Effect of active immunization to luteinizing hormone releasing hormone on serum and pituitary gonadotropins, testes and accessory sex organs in the male rat. J. Endocrinol 63: 399 (1974).

    Article  PubMed  CAS  Google Scholar 

  17. H.M. Fraser, R.M. Popkin, A.S. McNeilly and R.M. Sharpe, Changes in pituitary LHRH receptor levels in situations of increased or decreased gonadotrophin secretion in the male rat. Mol Cell Endocrinol 28:321 (1982).

    Article  PubMed  CAS  Google Scholar 

  18. B.D. Schanbacher, H.F. English, D. Gross, R.J. Santen, M.F. Walker and R.E. Falvo, Animal model of isolated gonadotropin deficiency I. Hormonal responses to LHRH immunoneutralization. J. Androl 4: 233 (1983).

    PubMed  CAS  Google Scholar 

  19. R.N. Clayton, R.M. Popkin and H.M. Fraser, Hypothalamic regulation of pituitary GnRH receptors: effects of gonadotrophinreleasing hormone immunoneutralisation. Endocrinology 110: 1116 (1982).

    Article  PubMed  CAS  Google Scholar 

  20. R.N. Clayton and K.J. Catt, Gonadotropin-releasing hormone receptors: characterization, physiological regulation, and relationship to reproductive function. Endocrine Reviews 2:198 (1981).

    Article  Google Scholar 

  21. H.F. English, B.D. Schanbacher, D. Gross, M.F. Walker, R.E. Falvo and R.J. Santen, Animal model of isolated gonadotropin deficiency II. Morphologic responses to LHRH immunoneutralization. J. Androl. 4: 240 (1983).

    PubMed  CAS  Google Scholar 

  22. G.A. Lincoln, H.M. Fraser and T.J. Fletcher, Antler growth in male red deer Cervus elaphus following active immunization against luteinizing hormone releasing hormone. J. Reprod. Fert. 66: 703 (1982).

    Article  CAS  Google Scholar 

  23. G.A. Lincoln, H.M. Fraser and T.J. Fletcher, Induction of early rutting in male red deer Cervus elaphus by melatonin and its dependence on LH-RH. J. Reprod Fert. 72: 339 (1985).

    Article  Google Scholar 

  24. B.J. Keeling and D.B. Crighton, Reversibility of the effects of active immunization against LH-RH in: “Immunological Aspects of Reproduction in mammals” D.B. Crighton ed., Butterworths, London (1984).

    Google Scholar 

  25. I.S. Robertson, J.C. Wilson, A.C. Rowland and H.M. Fraser, Further studies on immunological castration in male cattle. Vet. Rec 108: 381 (1981).

    Article  PubMed  CAS  Google Scholar 

  26. I.S. Robertson, H.M. Fraser, G.M. Innes and A.S. Jones, The effect of immunological castration on sexual and production characteristics in male cattle. Vet Rec 111: 529 (1982).

    PubMed  CAS  Google Scholar 

  27. J.K. Hodges and J.P. Hearn, Effects of immunisation against luteinizing hormone releasing hormone on reproduction of the marmoset monkey Callithrix jacchus Nature 265: 746 (1977).

    Article  CAS  Google Scholar 

  28. S.C. Chappel, W.E. Ellinwood, C. Huckins, D.C. Herbert and H.G. Spies, Active immunization of male rhesus monkeys against luteinizing hormone releasing hormone. Biol. Reprod 22:333 (1980).

    Article  PubMed  CAS  Google Scholar 

  29. R.M. Sharpe and H.M. Fraser, Leydig cell function in rats chronically deprived of normal gonadotrophic stimulation: the effect of treatment with hCG. Int. J. Androl 2: 395 (1979).

    Article  CAS  Google Scholar 

  30. H.M. Fraser and A.S. McNeilly, Differential effects of LH-RH immunoneutralization on LH and FSH secretion in the ewe. J. Reprod Fert 69: 569 (1983).

    Article  CAS  Google Scholar 

  31. A.S. McNeilly, H.M. Fraser and D.T. Baird, Effect of immunoneutralization of LH releasing hormone on LH, FSH and ovarian steroid secretion in the preovulatory phase of the oestrous cycle in the ewe. J. Endocr 101: 213 (1984).

    Article  PubMed  CAS  Google Scholar 

  32. M.C. Snabes and R.P. Kelch, Acute inhibitory effects of antiserum to gonadotropin-releasing hormone in ovariectomized rats. Neuroendocrinology 29:34 (1979).

    Article  PubMed  CAS  Google Scholar 

  33. M. Kawakami and T. Higuchi, Effects of active and passive immunization with LH-RH on gonadotrophin secretion and reproductive function in female rats. Acta endocr 91:616 (1979).

    PubMed  CAS  Google Scholar 

  34. B. Gledhill, H.M. Fraser and B.T. Donovan, Effect of passive immunization against LH-RH gonadotrophin secretion in the ferret. J. Reprod. Fert 64:19 (1982).

    Article  CAS  Google Scholar 

  35. J.T. McCormack, T.M. Plant, D.L. Hess and E. Knobil, The effect of luteinizing hormone releasing hormone (LHRH) antiserum administration on gonadotrophin secretion in the rhesus monkey. Endocrinology 100:663 (1977).

    Article  PubMed  CAS  Google Scholar 

  36. H.M. Fraser, A.S. McNeilly, M. Abbott, W.R.A. Brown and R.A. Steiner, The effect of LHRH immunoneutralization on fillicular development, the LH surge and luteal function in the stumptailed macaque. J. Reprod. Fert (1985).

    Google Scholar 

  37. C.A. Blake and R.P. Kelch, Administration of antiluteinizing hormone-releasing hormone serum to rats: effects on periovulatory secretion of luteinizing hormone and follicle-stimulating hormone. Endocrinology 109: 2175 (1981).

    Article  PubMed  CAS  Google Scholar 

  38. Y. Hasegawa, K. Miyamoto, C. Yazaki and M. Igarashi, Regulation of the second surge of follicle-stimulating hormone; effects of antiluteinizing hormone-releasing hormone serum and pentobarbital. Endocrinology 109:130 (1981).

    Article  PubMed  CAS  Google Scholar 

  39. K. Narayana and H. Dobson, Effect of administration of antibody against GnRH on preovulatory LH and FSH surges in the ewe. J. Reprod Fert. 57:65 (1979).

    Article  CAS  Google Scholar 

  40. H.M. Fraser and T.G. Baker, Changes in the ovaries of rats after immunization against luteinizing hormone releasing hormone. J. Endocr 77: 85 (1978).

    Article  PubMed  CAS  Google Scholar 

  41. M. Takahashi, J.J. Ford, K. Yoshinaga and R.O. Greep, Active immunization of female rats with luteinizing hormone releasing hormone (LHRH) Biol. Reprod. 17: 754.

    Google Scholar 

  42. H.M. Fraser, Active immunization of stumptailed macaque monkeys against luteinizing hormone releasing hormone, and its effects on menstrual cycles, ovarian steroids and positive feedback. J. Reprod Immunol. 5: 173 (1983).

    Article  PubMed  CAS  Google Scholar 

  43. H.M. Fraser, S.L. Jeffcoate, A. Gunn and D.T. Holland, Effect of active immunization to luteinizing hormone-releasing hormone on gonadotrophin levels in ovariectomized rats. J. Endocr 64:191 (1975).

    Article  PubMed  CAS  Google Scholar 

  44. I.J. Clarke, H.M. Fraser and A.S. McNeilly, Active immunization of ewes against luteinizing hormone releasing hormone and its effects on ovulation and gonadotrophin, prolactin and ovarian steroid secretion. J. Endocr 78:39 (1978).

    Article  PubMed  CAS  Google Scholar 

  45. H.M. Fraser, I.J. Clarke and A.S. McNeilly, Effect of oestrogen and an LH-RH agonist on the release of gonadotropins in ovariectomized ewes deprived of LH-RH. J. Reprod Fert 62:131 (1981).

    Article  CAS  Google Scholar 

  46. A.S. McNeilly, J.A. Jonassen and H.M. Fraser, Suppression of follicular development after long-term immunoneutralization of LHRH in the ewe. J. Reprod. Fert (submitted) (1985).

    Google Scholar 

  47. R.M. Popkin and H.M. Fraser, Changes in pituitary and ovarian LHRH receptors after active immunization of female rats against LH or LHRH. J. Reprod Fert. 73:491 (1985).

    Article  CAS  Google Scholar 

  48. R.T. Savoy-Moore, N.B. Schwartz, J.A. Duncan and J.C. Marshall, Pituitary gonadotropin-releasing hormone receptors during the rat oestrous cycle. Science 209:942 (1980).

    Article  PubMed  CAS  Google Scholar 

  49. R.N. Clayton, A.R. Solano, A. Garcia-Vela, M. Dufau and K.J. Catt, Regulation of pituitary receptors for gonadotropin-releasing hormone during the rat estrous cycle. Endocrinology 107:699 (1980).

    Article  PubMed  CAS  Google Scholar 

  50. R.M. Popkin and H.M. Fraser, The effects of immunoneutralization of LHRH or LH on pituitary LHRH receptors during the rat oestrous cycle. Mol Cell Endocr 33:305 (1983).

    Article  CAS  Google Scholar 

  51. A. de la Cruz, A. Arimura, K.G. de la Cruz and A.V. Schally, Effect of administration of anti-serum to luteinizing hormonereleasing hormone on gonadal function during the oestrous cycle in the hamster. Endocrinology 98:490 (1976).

    Article  PubMed  Google Scholar 

  52. H.M. Fraser and A.S. McNeilly Effect of immunoneutralization of LHRH on the estrogen-induced LH and FSH surge in the ewe. Biol Reprod 27: 548 (1982).

    Article  PubMed  CAS  Google Scholar 

  53. H.M. Fraser, D.T. Baird, G.I. McRai, J.J. Nestor and B.H. Vickery Suppression of luteal progesterone secretion in the stumptailed macaque by an antagonist analogue of luteinizing hormone releasing hormone. J. Endocr 104:R1–R4 (1985).

    Article  PubMed  CAS  Google Scholar 

  54. C. Das. Anti-GnRH monoclonals: pituitary and extrapituitary actions in control of fertility. This symposium.

    Google Scholar 

  55. N. Nishi, A. Arimura, K.G. de la Cruz and A.V. Schally, Termination of pregnancy by sheep anti-LH-RH gamma globulin in rats. Endocrinology 98:1024 (1976).

    Article  PubMed  CAS  Google Scholar 

  56. D.W. Silversides, B.D. Murphy, V. Misra and R.J. Mapletoft, Monoclonal antibodies against LHRH: development and immunoactivity in vivo and in vitro. J Reprod Immunol 7: 171 (1985).

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. MRC Reproductive Biology Unit, 37 Chalmers Street, Edinburgh, EH3 9EW, UK

    Hamish M. Fraser

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  1. Hamish M. Fraser
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Editors and Affiliations

  1. National Institute of Immunology, New Delhi, India

    G. P. Talwar

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© 1986 Plenum Press, New York

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Fraser, H.M. (1986). LHRH Immunoneutralization: Basic Studies and Prospects for Practical Application. In: Talwar, G.P. (eds) Immunological Approaches to Contraception and Promotion of Fertility. Reproductive Biology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5140-5_16

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  • DOI: https://doi.org/10.1007/978-1-4684-5140-5_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5142-9

  • Online ISBN: 978-1-4684-5140-5

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