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Action and interaction of growth hormone and the β-agonist, clenbuterol, on growth, body composition and protein turnover in dwarf mice

Published online by Cambridge University Press:  09 March 2007

P. C. Bates  and
J. M. Pell
P. C. Bates
Affiliation:
Endocrinology and Animal Physiology Department, AFRC Institute for Grassland and Animal Production, Hurley, Maidenhead, Berks SL6 5LR
J. M. Pell
Affiliation:
Nutrition Research Unit, London School of Hygiene and Tropical Medicine, 4 St Pancras Way, LondonNWI ZPE
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Abstract

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The responses of dwarf mice to dietary administration of clenbuterol (3 mg/kg diet), daily injections of growth hormone (15 μg/mouse per d) or both treatments combined were investigated and their actions, and any interactions, on whole-body growth, composition and protein metabolism, and muscle, liver and heart growth and protein metabolism, were studied at days 0, 4 and 8 of treatment. Growth hormone, with or without clenbuterol, induced an increase in body-weight growth and tail length growth; clenbuterol alone did not affect body-weight or tail length. Both growth hormone and clenbuterol reduced the percentage of whole-body fat and increased the protein:fat ratio. They also increased protein synthesis rates of whole body and muscle, although the magnitude of the increase was greater in response to growth hormone than to clenbuterol. Clenbuterol specifically induced growth of muscle, with a decrease in liver protein content, whereas growth hormone exhibited more general anabolic effects on tissue protein. Previous reports have suggested that effects of clenbuterol on skeletal muscle are mediated, at least in part, via decreased rates of protein degradation; we could find little evidence of any decrease in whole-body or tissue protein degradation and anabolic effects were largely due to increases in protein synthesis rates. However, small increases in muscle protein degradation rate were observed in response to growth hormone. Growth hormone induced a progressive increase in serum insulin-like growth factor-1 concentration, whereas there was no change with clenbuterol administration. Anabolic effects on whole-body and skeletal muscle protein metabolism, therefore, appear to be initially via independent mechanisms but are finally mediated by a common response (increased protein synthesis) in dwarf mice.

Keywords

Body compositionProtein turnoverGrowth hormoneClenbuterol
Type
Body Composition
Information
British Journal of Nutrition , Volume 65 , Issue 2 , March 1991 , pp. 115 - 129
Copyright
Copyright © The Nutrition Society 1991

References

REFERENCES

Albertsson-Wikland, K., Eden, S. & Isaksson, O. (1980). Analysis of early responses to growth hormone on amino acid transport and protein synthesis in diaphragms of young normal rats. Endocrinology 106, 291–297.CrossRefGoogle Scholar
Ayling, C. M., Moreland, B. H., Zanelli, J. M. & Schulster, D. (1989). Human growth hormone treatment of hypophysectomised rats increases the proportion of type-1 fibres in skeletal muscle. Journal of Endocrinology 123, 429–435.CrossRefGoogle Scholar
Babij, P. & Booth, F. W. (1988). Clenbuterol prevents or inhibits loss of specific mRNAs in atrophying rat skeletal muscle. American Journal of Physiology 254, C657–C660.CrossRefGoogle ScholarPubMed
Baker, P. K., Dalrymple, R. H., Ingle, D. L. & Ricks, C. A. (1984). Use of a β-adrenergic agonist to alter muscle and fat deposition in lambs. Journal of Animal Science 59, 1256–1261.CrossRefGoogle Scholar
Bates, P. C. & Holder, A. T. (1988). The anabolic actions of growth hormone and thyroxine on protein metabolism in Snell dwarf and normal mice. Journal of Endocrinology 119, 31–41.Google Scholar
Bates, P. C. & Millward, D. J. (1983). Myofibrillar protein turnover: synthesis rate of myofibrillar and sarcoplasmic protein fractions in different muscles and the changes observed during post-natal development and in response to feeding and fasting. Biochemical Journal 214, 587–592.CrossRefGoogle Scholar
Beerman, D. H., Boyd, R. D., Fishell, V. K. & Ross, D. A. (1987a). A comparison of the repartitioning effects of cimaterol and somatotropin on skeletal muscle growth. Federation Proceedings 46, 1020.Google Scholar
Beerman, D. H., Butler, W. R., Hogue, D. E., Fishell, V. K., Dalrymple, R. H., Ricks, C. A. & Scanes, C. G. (1987b). Cimaterol-induced muscle hypertrophy and altered endocrine status in lambs. Journal of Animal Science 65, 1514–1524.CrossRefGoogle Scholar
Bohorov, O., Buttery, P. J., Correia, J. H. R. D. & Soar, J. B. (1987). The effect of the β2-adrenergic agonist clenbuterol or implantation with oestradiol plus trenbolone acetate on protein metabolism in wether lambs. British Journal of Nutrition 57, 99–107.CrossRefGoogle ScholarPubMed
Butler-Browne, G. S., Pruliere, G., Cambon, N. & Whalen, R. G. (1987). Influence of the dwarf mouse mutation on skeletal and cardiac myosin isoforms. Journal of Biological Chemistry 262, 15188–15193.CrossRefGoogle ScholarPubMed
Carroll, M. J., Lister, C. A., Sennitt, M. V., Stewart-Long, N. & Cawthorne, M. A. (1985). Improved glycemic control in C-57BI/KsG (BB-DB) mice after treatment with the thermogenic β-adrenoceptor-agonist BRL 26830. Diabetes 34, 1198–1204.CrossRefGoogle Scholar
Daughaday, W. H., Parker, K. A., Borowsky, S., Trivedi, B. & Kapadia, M. (1982). Measurement of somatomedin-related peptides in fetal, neonatal, and maternal rat serum by insulin-like growth factor (IGF) 1 radioimmunoassay, IGF-2 radioreceptor assay (RRA), and multiplication stimulating activity RRA after acidethanol extraction. Endocrinology 110, 575–580.Google Scholar
Deshaies, Y., Willemot, J. & Leblac, J. (1981). Protein synthesis, amino acid uptake, and pools during isoproteronol-induced hypertrophy of the rat heart and tibialis muscle. Canadian Journal of Physiology and Pharmacology 59, 113–121.CrossRefGoogle Scholar
Eisemann, J. H., Huntington, G. B. & Ferrell, C. L. (1988). Effects of dietary clenbuterol on metabolism of the hindquarters in steers. Journal of Animal Science 66, 342–353.Google Scholar
Emery, P. W., Rothwell, N. J., Stock, M. J. & Winter, P. D. (1984). Chronic effects of β2-adrenergic agonists on body composition and protein synthesis in the rat. Bioscience Reports 4, 83–91.CrossRefGoogle Scholar
Flaim, K. E., Li, J. B. & Jefferson, L. S. (1978). Protein turnover in rat skeletal muscle: effects of hypophysectomy and growth hormone. American Journal of Physiology 234, E38–E43.Google ScholarPubMed
Garlick, P. J., McNurlan, M. A. & Preedy, V. R. (1980). A rapid and convenient technique for measuring the rate of protein synthesis in tissues by injection of [3H]phenylalanine. Biochemical Journal 192, 719–723.CrossRefGoogle ScholarPubMed
Hart, I. C. & Johnsson, I. D. (1986). Growth hormone and growth in meat-producing animals. In Control and Manipulation of Animal Growth, pp. 135–159 [Buttery, P. J., Haynes, N. B. and Lindsey, D. B., editors]. London: Butterworths.CrossRefGoogle Scholar
Higgins, J. A., Lasslett, Y. V., Bardsley, R. G. & Buttery, P. J. (1988). The relationships between dietary restriction or clenbuterol (a selective β2-agonist) treatment on muscle growth and calpain proteinase (EC 3. 4. 22. 17) and calpastatin activities in lambs. British Journal of Nutrition 60, 645–652.Google Scholar
Holder, A. T., Clark, R. C. & Preece, M. A. (1982). The relationship between body weight, tail length and uptake of 35SO-24 into costal cartilage in vivo in growth hormone treated hypopituitary Snell dwarf mice: basis for a bioassay for growth hormone. IRCS Medical Science 10, 697.Google Scholar
Hovell, F. D. deB., Kyle, D. J., Reeds, P. J. & Beerman, D. H. (1988). The effect of β2-agonists on the endogenous nitrogen loss of sheep. Proceedings of the Nutriton Society: 47, 13A.Google Scholar
James, S. & Barker, H. D. (1987). Effect of clenbuterol on the growth and carcass composition of hypophysectomised rats in the presence or absence of growth hormone. Proceedings of the Nutrition Society 46, 108A.Google Scholar
Kim, Y. S., Lee, Y. B. & Dalrymple, R. H. (1987). Effect of the repartitioning agent cimaterol on growth, carcass and skeletal muscle characteristics in lambs. Journal of Animal Science 65, 1392–1399.CrossRefGoogle ScholarPubMed
Laurent, G. J., Sparrow, M. P., Bates, P. C. & Millward, D. J. (1978). Turnover of muscle protein in the fowl. Biochemical Journal 176, 419–427.CrossRefGoogle ScholarPubMed
Lavenstein, B., Engel, W. K., Reddy, N. B. & Carroll, S. (1979). Autoradiographic visualisation of β-adrenergic receptors in normal and denervated skeletal muscle. Journal of Histochemistry and Cytochemistry 27, 1308–1311.Google Scholar
Lowry, O. H., Rosebrough, N., Farr, A. L. & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193, 265–275.CrossRefGoogle ScholarPubMed
MacRae, J. C., Skene, P. A., Connell, A., Buchan, V. & Lobley, G. E. (1988). The action of the β-agonist clenbuterol on protein and energy metabolism in fattening wether lambs. British Journal of Nutrition 59, 457–465.CrossRefGoogle ScholarPubMed
Maltin, C. A., Delday, M. I. & Reeds, P. J. (1986a). The effect of a growth promoting drug, clenbuterol, on fibre frequency and area in hind limb muscles from young male rats. Bioscience Reports 6, 293–299.CrossRefGoogle ScholarPubMed
Maltin, C. A., Hay, S. M., Delday, M. I., Smith, F. J., Lobley, G. E. & Reeds, P. J. (1987). Clenbuterol, a beta-agonist, induces growth in innervated and denervated rat soleus muscles via apparently different mechanisms. Bioscience Reports 7, 525–532.CrossRefGoogle ScholarPubMed
Millward, D. J., Nnanyelugo, D. O., James, W. P. T. & Garlick, P. J. (1974). Protein metabolism in skeletal muscle: the effect of feeding and fasting on muscle RNA, free amino acids and plasma insulin concentrations. Biochemical Journal 150, 235–243.CrossRefGoogle Scholar
Millward, D. J., Odedra, B. O. & Bates, P. C. (1983). Role of insulin, corticosterone and other factors in the acute recovery of muscle protein synthesis on re-feeding food-deprived rats. Biochemical Journal 216, 583–587.Google Scholar
Odedra, B. O., Dalal, S. S. & Millward, D. J. (1982). Muscle protein synthesis in the streptozotocin diabetic rat: a possible role for corticosterone in the insensitivity of insulin infusion in vivo. Biochemical Journal 202, 363–368.Google Scholar
Pell, J. M. & Bates, P. C. (1987). Collagen and non-collagen protein turnover in skeletal muscle of growth hormone-treated lambs. Journal of Endocrinology 115, R1–R4.Google Scholar
Reeds, P. J., Hay, S. M., Dorward, P. M. & Palmer, R. M. (1986). Stimulation of muscle growth by clenbuterol: lack of effect on muscle protein biosynthesis. British Journal of Nutrition 56, 249–258.CrossRefGoogle ScholarPubMed
Ricks, C. A., Dalrymple, R. H., Baker, P. K. & Ingle, D. L. (1984). Use of a β-agonist to alter fat and muscle deposition in steers. Journal of Animal Science 59, 1247–1255.CrossRefGoogle Scholar
Sainz, R. D. & Wolff, J. E. (1988). Effects of the β-agonist, cimaterol, on growth, body composition and energy expenditure in rats. British Journal of Nutrition 60, 85–90.CrossRefGoogle ScholarPubMed
Snell, G. D. (1929). Dwarf, a new mendelian recessive character of the house mouse. Proceedings of the National Academy of Sciences, USA 15, 733–734.Google Scholar
Thiel, L. F., Beerman, D. H., Fishell, V. K. & Crooker, B. A. (1987). Effects of cimaterol on growth of hypophysectomised rats. Federation Proceedings 46, 1176.Google Scholar
van Buul-Offers, S. (1983). Hormonal and other inherited growth disturbances in mice with special reference to the Snell dwarf mouse. Acta Endocrinologica 258, 1–47.Google Scholar
Wallis, M. (1980). Receptors for growth hormone, prolactin, and the somatomedins. In Cellular Receptors for Hormones and Neurotransmitters, pp. 163–183 [D. Schulster and Levitsky, A., editors]. Chichester: Wiley & Sons.Google Scholar
Wang, S.-Y. & Beerman, D. H. (1988). Reduced calcium-dependent proteinase activity in cimaterol-induced muscle hypertrophy in lambs. Journal of Animal Science 66, 2545–2550.CrossRefGoogle ScholarPubMed
Webster, B. A., Vigna, S. R. & Paquette, T. (1986). Acute exercise, epinephrine, and diabetes enhance insulin binding to skeletal muscle. American Journal of Physiology 250, E186–E197.Google ScholarPubMed
Williams, P. E. V. (1987). The use of β-agonists as a means of altering body composition in livestock species. Nutrition Abstracts and Reviews (B) 57, 453–464.Google Scholar
Williams, P. E. V., Innes, G. M., Ogden, K. & James, S. (1987a). The effects of a combination of the β-agonist clenbuterol and bovine pituitary growth hormone on growth of milk-fed calves. Animal Production 44, 475.Google Scholar
Williams, P. E. V., Pagliani, L., Innes, G. M., Pennie, K. & Garthwaite, P. (1987b). Effects of a β-agonist (clenbuterol) on growth, carcass composition, protein and energy metabolism of veal calves. British Journal of Nutrition 57, 417–428.CrossRefGoogle ScholarPubMed
Williams, R. S., Caron, M. G. & Daniel, K. (1984). Skeletal muscle β-adrenergic receptors: variations due to fibre type and training. American Journal of Physiology 246, E160–E167.Google ScholarPubMed
Zeman, R. J., Ludemann, R., Easton, T. G. & Etlinger, J. D. (1988). Slow to fast alterations in skeletal muscle fibres caused by clenbuterol, a β2-receptor agonist. American Journal of Physiology 254, E726–E732.Google Scholar