Hostname: page-component-77c89778f8-5wvtr Total loading time: 0 Render date: 2024-07-17T16:46:04.294Z Has data issue: false hasContentIssue false
  • English
  • Français

Immunomodulatory approaches for regulation of growth and body composition

Published online by Cambridge University Press:  02 September 2010

D.J. Flint
D.J. Flint
Affiliation:
Hannah Resarch Institute, Ayr KA6 5HL
Get access

Abstract

Hormonal growth promoters (growth hormone (GH), β-adrenergic agonists, steroids) which improve growth rate and/or lean: fat ratios in the carcass have received considerable adverse publicity and are either banned or have no licence for their use in countries of the European Community. This has led to the development of a number of techniques, involving the use of antibodies, aimed at regulating metabolic processes involved in determining growth and body composition.

A number of these approaches have focused upon the GH axis, for example immunoneutralization of somatostatin (which normally inhibits GH secretion) to improve growth, the use of antibodies to GH which can enhance its effects in vivo and the development of antibodies which mimic the actions of GH. Although immunization against somatostatin has led to increased growth rates in a number of studies other studies have failed to demonstrate such an effect. A precise understanding of the mechanism of action of this approach is required before we can begin to understand why success is not assured. Antibodies which enhance GH action clearly do work reproducibly but the major problem in developing this approach is to produce an inexpensive peptide immunogen (its sequence derived from GH) which can be used to actively immunize animals so that their own antibodies enhance endogenous GH activity. Anti-idiotypic mimics of GH have also been produced which have GH actions in vivo but again this approach is of limited value until appropriate vaccines can be developed.

A different approach to the problem of excess fat deposition involves the use of antibodies directed against the plasma membranes of adipocytes in order to elicit their destruction and thereby limit the storage capacity for fat. This technique has been demonstrated in rats, sheep and pigs in both passive and active immunization techniques. Once again, however, this promising approach is limited by the lack of a commercially suitable vaccine. The identification of individual membrane proteins which are antigenic has been achieved and this provides the prospect of producing recombinant DNA-derived vaccines.

Whether these new approaches will be perceived as acceptable to the general public remains a serious concern and a potential limitation to their development as many would-be sponsors cut back their support for research in these areas.

Keywords

body compositiongrowthimmunological factors
Type
Research Article
Information
Animal Production , Volume 58 , Issue 3 , June 1994 , pp. 301 - 312
Copyright
Copyright © British Society of Animal Science 1994

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abdel-Meguid, S. S., Shieh, H. S., Smith, W. W., Dayringer, H. E., Violand, B. N. and Bentle, L. A. 1987. Three-dimensional structure of a genetically engineered variant of porcine growth hormone. Proceedings of the National Academy of Sciences, USA 84: 6434–6437.CrossRefGoogle ScholarPubMed
Adams, T. E., Baker, L., Fiddes, R. J. and Brandon, M. R. 1990. The sheep growth hormone receptor: molecular cloning and ontogeny of mRNA expression in the liver. Molecular and Cellular Endocrinology 73: 135–145.CrossRefGoogle ScholarPubMed
Arimura, A., Smith, W. D. and Schally, A. V. 1976. Blockage of the stress-induced decrease in blood GH by anti-somatostatin serum in rats. Endocrinology 98: 540–543.CrossRefGoogle Scholar
Aston, R., Holder, A. T., Preece, M. A. and Ivanyi, J. 1986. Potentiation of the somatogenic and lactogenic activity of human growth hormone with monoclonal antibodies. journal of Endocrinology 110: 381–388.CrossRefGoogle ScholarPubMed
Barnard, R., Bundesen, P. G., Rylatt, D. B. and Waters, M. J. 1984. Monoclonal antibodies to the rabbit liver growth hormone receptor: production and characterization. Endocrinology 115: 1805–1813.CrossRefGoogle Scholar
Barnard, R., Bundesen, P. G., Rylatt, D. B. and Waters, M. J. 1985. Evidence from the use of monoclonal antibody probes for structural heterogeneity of the growth hormone receptor. Biochemical Journal 231: 459–468.CrossRefGoogle ScholarPubMed
Bass, J. J., Gluckman, P. D., Fairclough, R. J., Peterson, A., Davis, S. R. and Carter, W. D. 1987. Effect of nutrition and immunization against somatostatin on growth and insulin-like growth factors in sheep. Journal of Endocrinology 112: 27–31.CrossRefGoogle ScholarPubMed
Bass, S. H., Mulkerrin, M. G. and Wells, J. A. 1991. A systematic mutational analysis of hormone-binding determinants in the human growth hormone receptor. Proceedings of the National Academy of Sciences of the U.S.A. 88: 4498–4502.CrossRefGoogle ScholarPubMed
Baumann, G., Stolar, M. W., Amburn, K., Barsano, C. P. and De Vries, B. C. 1986. A specific growth hormone binding protein in human plasma: initial characterization. Journal of Clinical Endocrinology and Metabolism 62: 134–141.CrossRefGoogle ScholarPubMed
Baumbach, W. R., Horner, D. L. and Logan, J. S. 1989. The growth hormone-binding protein in rat serum is an alternatively spliced form of the rat growth hormone receptor. Genes and Development 3: 1199–1205.CrossRefGoogle ScholarPubMed
Bozikov, V. 1980. Somatostatin. Diabetologia Croatica IX-1: 8–58.Google Scholar
Brumby, P. J. 1959. The influence of growth hormone on growth in young cattle. New Zealand Journal of Agricultural Research 2: 683–686.CrossRefGoogle Scholar
Butterwith, S. C, Kestin, S., Griffin, H. D., Beattie, J. and Flint, D. J. 1992. Identification of chicken (Gallus domesticus) adipocyte plasma membrane and differentiation specific proteins using SDS-PAGE and Western blotting. Comparative Biochemistry and Physiology 101B: 147–51.Google Scholar
Butterwith, S. C, Kestin, S., Griffin, H. D. and Flint, D. J. 1989. Cytoxic antibodies to chicken adipocytes and their precursors: lack of tissue specificity. British Poultry Science 30: 371–78.CrossRefGoogle Scholar
Cioffi, J. A., Wang, X. and Kopchick, J. J. 1990. Porcine growth hormone receptor cDNA sequence. Nucleic Acids Research 18: 6451.CrossRefGoogle ScholarPubMed
Cohick, W. S. and Clemmons, D. R. 1993. The insulin-like growth factors. Annual Review of Physiology 55: 131–153.CrossRefGoogle ScholarPubMed
Cunningham, B. C. and Wells, J. A. 1991. Rational design of receptor-specific variants of human growth hormone. Proceedings of the National Academy of Sciences, USA 88: 3407–3411.CrossRefGoogle ScholarPubMed
De Larco, J. E. and Todaro, G. J. 1978. Growth factors from murine sarcoma virus-transformed cells. Proceedings of the National Academy of Sciences, USA 75: 4001–4005.CrossRefGoogle ScholarPubMed
Dubreuil, P., Pelletier, G., Peticlerc, D., Lapierre, H., Gaudreau, P. and Brazeau, P. 1989. Effects of active immunization against somatostatin on serum growth hormone concentration in growing pigs: influence of fasting and repetitive somatocrinin injections. Endocrinology 125: 1378–1384.CrossRefGoogle ScholarPubMed
Dulor, J. P., Reyne, Y. and Nougues, J. 1990. In vivo effects of a treatment with antibodies to adipocyte plasma membranes in the rabbit. Reproduccion Nutrition et Devcloppement 30: 49–58.CrossRefGoogle ScholarPubMed
Elbashir, M. I., Brodin, T., Akestrom, B. and Donner, J. 1990. Monoclonal antibodies to the pituitary growth hormone receptor by the anti-idiotypic approach: production and initial characterization. Biochemical Journal 266: 467–474.CrossRefGoogle Scholar
Etherton, T. D., Wiggins, J. P., Evock, C. M., Chung, C. S., Rebhun, J. F., Walton, P. E. and Steele, N. C. 1987. Stimulation of pig growth performance by porcine growth hormone: determination of the dose-response relationship. Journal of Animal Science 64: 433–443.CrossRefGoogle ScholarPubMed
Fadlalla, A. M., Spencer, G. S. G. and Lister, D. 1985. The effect of passive immunization against somatostatin on growth and concentration of somatotropin in plasma of Holstein calves. Domestic Animal Endocrinology 5: 35–41.Google Scholar
Farid, N. R., Pepper, B., Urbina-Briones, R. and Islam, N. R. 1982. Biological activity of anti-thyrotropin anti-idiotypic antibody. Journal of Cellular Biochemistry 19: 305–313CrossRefGoogle ScholarPubMed
Fitzsimons, J. M. and Hanrahan, J. P. 1984. Effect of active immunization against somatostatin on the growth rate of lambs. An Foras Taluntais Animal Production Report, pp. 80–81.Google Scholar
Flint, D. J. 1990. Immunomodulatory approaches for manipulation of animal growth, body composition and fecundity. Biotechnology and Genetic Engineering Reviews 8: 97–131.CrossRefGoogle Scholar
Flint, D. J., Coggrave, H., Futter, C. E., Gardner, M. J. and Clarke, T. J. 1986. Stimulatory and cytotoxic effects of an antiserum to adipocyte plasma membranes on adipose tissue metabolism in vitro and in vivo. International Journal of Obesity 10: 69–77.Google ScholarPubMed
Flint, D. J. and Gardner, M. J. 1989. Inhibition of neonatal rat growth and circulating concentrations of insulin-like growth factor-I using an antiserum to rat growth hormone. journal of Endocrinology 122: 79–86.CrossRefGoogle ScholarPubMed
Flint, D. J. and Gardner, M. J. 1993. Influence of growth hormone deficiency on growth and body composition in rats: site-specific effects upon adipose tissue development. Journal of Endocrinology 137: 203–211.CrossRefGoogle ScholarPubMed
Frick, G. P. and Goodman, H. M. 1992. Characterization of the short isoform of the growth hormone receptor synthesized by rat adipocytes. Endocrinology 131: 3083–3090.CrossRefGoogle ScholarPubMed
Fuh, G., Cunningham, B. C., Fukunaga, R., Nagata, S., Goeddel, D. V. and Wells, J. A. 1992. Rational design of potent antagonists to the human growth hormone receptor. Science, Washington 256: 1677–1680.CrossRefGoogle Scholar
Futter, C. E. and Flint, D. J. 1987. Long-term reduction of adiposity in rats after passive immunization with antibodies to rat fat cell plasma membranes. In Recent advances in obesity research V (ed. Berry, E. M.), pp. 181–185. John Libbey, London.Google Scholar
Futter, C. E., Panton, D., Kestin, S. and Flint, D. J. 1992. Mechanism of action of cytotoxic antibodies to adipocytes on adipose tissue, liver and food intake in the rat. International Journal of Obesity 16: 615–622.Google ScholarPubMed
Galbraith, H., Wigzell, S., Scaife, J. R. and Henderson, G. D. 1985. Growth and metabolic response of rapidly-growing male castrate lambs to immunization against somatostatin. Animal Production 40: 523 (abstr.).Google Scholar
Gardner, M. J. and Flint, D. J. 1990. Long-term reductions in GH, insulin-like growth factor-I and body weight gain in rats treated neonatally with antibodies to rat GH. Journal of Endocrinology 124: 381–386.CrossRefGoogle ScholarPubMed
Gardner, M. J., Morrison, C. A., Stevenson, L. Q. and Flint, D. J. 1990. Production of anti-idiotypic antisera to rat GH antibodies capable of binding to GH receptors and increasing body weight gain in hypophysectomized rats. Journal of Endocrinology 125: 53–59.CrossRefGoogle ScholarPubMed
Hauser, S. D., McGrath, M. F., Collier, R. J. and Krivi, G. G. 1990. Cloning and in vivo expression of bovine growth hormone receptor mRNA. Molecular and Cellular Endocrinology 72: 187–200.CrossRefGoogle ScholarPubMed
Holder, A. T. and Aston, R. 1989. Antigen-antibody complexes that enhance growth. In Biotechnology in growth regulation (ed. Heap, R. B., Prosser, C. G. and Lamming, G. E.), pp. 167–177. Butterworths, London.CrossRefGoogle Scholar
Ignotz, R. A. and Massague, J. 1985. Type β transforming growth factor controls the adipogenic differentiation of 3T3 fibroblasts. Proceedings of the National Academy of Sciences, USA 82: 8530–8534.CrossRefGoogle ScholarPubMed
Kestin, S., Kennedy, R., Tonner, E., Kiernan, M., Cryer, A., Griffin, H., Butterwith, S., Rhind, S. and Flint, D. J. 1993. Decreased fat content and increased lean in pigs treated with antibodies to adipocyte plasma membranes. journal of Animal Science 71: 1486–1494.CrossRefGoogle ScholarPubMed
Laarveld, B., Chaplin, R. K. and Kerr, D. E. 1986. Somatostatin immunization and growth of lambs. Canadian Journal of Animal Science 66: 77–83.CrossRefGoogle Scholar
Lawrence, M. E., Schelling, G. T., Byers, F. M. and Greene, L. W. 1986. Improvement of growth and feed efficiency in cattle by active immunization against somatostatin. Journal of Animal Science 63: suppi, p. 215.Google Scholar
Leung, D. W., Spencer, S. A., Cachianes, G., Hammonds, R. G., Collins, C., Henzel, W. J., Barnard, R., Waters, M. J. and Wood, W. I. 1987. Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature, London 330: 537–543.CrossRefGoogle ScholarPubMed
Liebhaber, S. A., Urbanek, M., Ray, J., Tuan, R. S. and Cooke, N. E. 1989. Characterization and histological location of human growth hormone — variant gene expression in the placenta. Journal of Clinical Investigation 83: 1985–1991.CrossRefGoogle Scholar
Lim, L., Spencer, S. A., McKay, P. and Waters, M. J. 1990. Regulation of growth hormone (GH) bioactivity by a recombinant human GH-binding protein. Endocrinology 127: 1287–1291.CrossRefGoogle ScholarPubMed
Machlin, L. J. 1972. Effect of porcine growth hormone on growth and carcass composition of the pig. Journal of Animal Science 35: 794–800.CrossRefGoogle ScholarPubMed
Massaugé, J., Cheifetz, S., Endo, T. and Nadal-Ginard, B. 1986. Type β-transforming growth factor is an inhibitor of myogenic differentiation. Proceedings of the National Academy of Sciences, USA 83: 8206–8210.CrossRefGoogle Scholar
Mathews, L. S., Enberg, B. and Norstedt, G. 1989. Regulation of rat growth hormone receptor gene expression. Journal of Biological Chemistry 264: 9905–9910.CrossRefGoogle ScholarPubMed
Moloney, A. P. 1990. Immunizing against adipose plasma membranes to reduce body fat: effects on plasma metabolites and insulin. Biochemical Society Transactions 18: 336–337.CrossRefGoogle ScholarPubMed
Moloney, A. P. and Allen, P. 1989. Growth and weights of abdominal and carcass fat in sheep immunized against adipose cell membranes. Proceedings of the Nutrition Society 48: 14A (abstr.).Google Scholar
Muir, L. A., Wien, S., Duquette, P. F., Rickes, E. L. and Cordes, E. H. 1983. Effects of exogenous growth hormone and diethylstibestrol on growth and carcass composition of growing lambs. Journal of Animal Science 56: 1315–1323.CrossRefGoogle Scholar
Nassar, A. H. and Hu, C. Y. 1991. Growth and carcass characteristics of lambs passively immunized with antibodies developed against ovine adipocyte plasma membranes. Journal of Animal Science 69: 578–586.CrossRefGoogle ScholarPubMed
Olson, E. N., Sternberg, E., Hu, J. S., Spizz, G. and Wilcox, C. 1986. Regulation of myogenic differentiation by type β transforming growth factor. Journal of Cell Biology 103: 1799–1805.CrossRefGoogle ScholarPubMed
Panton, D., Futter, C., Kestin, S. and Flint, D. 1990. Increased growth and protein deposition in rats treated with antibodies to adipocytes. American Journal of Physiology 258: E985–E989.Google ScholarPubMed
Pell, J. M., Elcock, C., Walsh, A., Trigg, T. and Aston, R. 1989. Potentiation of growth hormone activity using a polyclonal antibody of restricted specificity. In Biotechnology in growth regulation (ed. Heap, R. B., Prosser, C. G. and Lamming, G. E.), p. 259. Butterworths, London.CrossRefGoogle Scholar
Pell, J. M., Johnsson, I. E., Pullar, R. A., Morrell, D. J., Hart, I. C., Holder, A. T. and Aston, R. 1989. Potentiation of growth hormone activity in sheep using monoclonal antibodies. Journal of Endocrinology 120: R15–R18.CrossRefGoogle ScholarPubMed
Peticlerc, D., Pelletier, G., Dubreuil, P., Lapierre, H., Farmer, C. and Brazeau, P. 1988. Effects of active immunization against somatostatin and growth hormone-releasing factor infusion on growth hormone secretion in dairy heifers. Journal of Animal Science 66: suppl., p. 389 (abstr.).Google Scholar
Reichlin, S. 1983. Somatostatin. Neiv England Journal of Medicine 309: 1495–1501.CrossRefGoogle ScholarPubMed
Reisine, T. 1985. Multiple mechanism of somatostatin inhibition of adrenocorticotropin release from mouse anterior pituitary tumor cells. Endocrinology 116: 2259–2266.CrossRefGoogle ScholarPubMed
Retegui, L. A., Milne, R. W., Cambiaso, C. L. and Masson, P. L. 1982. The recognition by monoclonal antibodies of various portions of a major antigenic site of human growth hormone. Molecular Immunology 19: 865–875.CrossRefGoogle Scholar
Schreiber, A. B., Courgud, P. D., Andew, C. L., Vray, B. and Strosberg, A. D. 1980. Anti-alprenolol anti-idiotypic antibodies bind to β-adrenergic receptors and modulate catecholamine sensitive adenylate cyclase. Proceedings of the National Academy of Sciences, USA 77: 7385–7389.CrossRefGoogle ScholarPubMed
Seeburg, P. H. 1982. The human growth hormone gene family: nucleotide sequences show recent divergence and predict a new polypeptide hormone. DNA 1: 239–249.CrossRefGoogle ScholarPubMed
Sege, K. and Peterson, P. A. 1978. Use of anti-idiotypic antibodies as cell surface receptor probes. Proceedings of the National Academy of Sciences, USA 75: 2443–2447.CrossRefGoogle ScholarPubMed
Silva, C. M., Weber, M. J. and Thorner, M. O. 1993. Stimulation of tyrosine phosphorylation in human cells by activation of the growth hormone receptor. Endocrinology 132: 101–108.CrossRefGoogle ScholarPubMed
Smith, W. C., Kuniyoshi, J. and Talamantes, F. 1989. Mouse serum growth hormone (GH) binding protein has GH receptor extracellular and substituted transmembrane domains. Molecular Endocrinology 3: 984–990.CrossRefGoogle ScholarPubMed
Sotiropoulos, A., Goujon, L., Simonin, G., Kelly, P. A., Postel-Vinay, M.-C. and Finidori, J. 1993. Evidence for generation of the growth hormone-binding protein through proteolysis of the growth hormone membrane receptor. Endocrinology 132: 1863–1865.CrossRefGoogle ScholarPubMed
Spencer, G. S. G., Garssen, G. J. and Hart, I. C. 1983a. A novel approach to growth promotion using autoimmunization against somatostatin. I. Effects on growth and hormone levels in lambs. Livestock Production Science 10: 25–37.CrossRefGoogle Scholar
Spencer, G. S. G., Garssen, G. J. and Hart, I. C. 1983b. A novel approach to growth promotion using autoimmunization against somatostatin. II. Effects on appetite, carcass composition and food utilization in lambs. Livestock Production Science 10: 469–477.CrossRefGoogle Scholar
Stewart, C. E. H., Bates, P. C., Calder, T. A., Woodall, S. M. and Pell, J. M. 1993. Potentiation of insulin-like growth factor-I (IGF-I) activity by an antibody: supportive evidence for enhancement of IGF-I bioavailability in vivo by IGF binding protein. Endocrinology 133: 1462–1465.CrossRefGoogle Scholar
Tashijian, A. J., Voelkel, E. F., Lazzaro, M., Singer, F. R., Roberts, A. B., Derynck, R., Winkler, M. E. and Levine, L. 1985. Alpha and beta transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria. Proceedings of the National Academy of Sciences, USA 82: 4535–4538.CrossRefGoogle Scholar
Terry, L. C. and Martin, J. B. 1981. The effects of lateral hypothalamic-medial forebrain somatostatin antiserum on pulsatile growth hormone secretion in freely behaving rats: evidence for a dual regulatory mechanism. Endocrinology 109: 622–627.CrossRefGoogle ScholarPubMed
Thomas, H., Green, I. C., Wallis, M. and Aston, R. 1987. Heterogeneity of growth-hormone receptors detected with monoclonal antibodies to human growth hormone. Biochemical Journal 243: 365–372.CrossRefGoogle ScholarPubMed
Trivedi, B. and Daughaday, W. H. 1988. Release of growth hormone binding protein from IM-9 lymphocytes by endopeptidase is dependent on sulfhydryl group inactivation. Endocrinology 123: 2201–2206.CrossRefGoogle ScholarPubMed
Trout, W. E. and Schanbacher, B. D. 1990. Growth hormone and insulin-like growth factor-I responses in steers actively immunized against somatostatin or growth hormone-releasing factor. Journal of Endocrinology 125: 123–129.CrossRefGoogle ScholarPubMed
Urbanek, M., MacLeod, J. N., Cooke, N. E. and Leibhaber, S. A. 1992. Expression of a human growth hormone (hGH) receptor isoform is predicted by tissue-specific alternative splicing of exon 3 of the hGH receptor gene transcript. Molecular Endocrinology 6: 279–287.Google ScholarPubMed
Varner, M. A., Davis, S. L. and Reeves, J. L. 1980. Temporal serum concentrations of growth hormone, thyrotropin, insulin and glucagon in sheep immunized against somatostatin. Endocrinology 106: 1027–1032.CrossRefGoogle ScholarPubMed
Vos, A. M. de, Ultsch, M. and Kossiakoff, A. A. 1992. Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science, Washington 255: 306–312.CrossRefGoogle ScholarPubMed
Wallis, M. 1982. Molecular basis of growth hormone deficiency. Nature, London 296: 112–113.CrossRefGoogle ScholarPubMed
Wallis, M., Daniels, M., Ray, K. P., Cottingham, J. D. and Aston, R. 1987. Monoclonal antibodies to bovine growth hormone potentiate effects of the hormone on somatomedin-C levels and growth of hypophysectomized rats. Biochemical and Biophysical Research Communications 149: 187–193.CrossRefGoogle ScholarPubMed
Wasserman, N. H., Penn, A. S., Freimuth, P. I., Treptow, N., Wentzel, S., Cleveland, W. L. and Erlanger, B. F. 1982. Anti-idiotypic route to anti-acetylcholine receptor antibodies and experimental myasthenia gravis. Proceedings of the National Academy of Sciences, USA 79: 4810–4814.CrossRefGoogle Scholar
Yamada, K., Lipson, K. E. and Donner, D. B. 1987. Structure and proteolysis of the growth hormone receptor on rat hepatocytes. Biochemistry 26: 4438–4443.CrossRefGoogle ScholarPubMed
Ymer, S. I. and Herington, A. C. 1985. Evidence for the specific binding of growth hormone to a receptor-like protein in rabbit serum. Molecular and Cellular Endocrinology 41: 153–161.CrossRefGoogle ScholarPubMed