observed in mixed-fiber type muscles. It is apparent that type-II fibers (i.e., fast-contracting, mixed glycolytic-oxidative) account for the greater portion of hypertrophy when compared with the type-I fibers (slow contracting oxidative) (reviewed by Yang and McElligott, 1989). There is evidence that long-term treatment can cause an increase in the proportions of type-II fibers (Beermann et al., 1987; Zeman et al., 1988), although this has not always been observed (Kim et al., 1987).

Increases in muscle protein deposition (growth) can either be a result of changes in the rate of protein synthesis or in the rate of degradation or both. Several studies suggest that β-agonists reduce the rate of muscle protein degradation in sheep (Bohorov et al., 1987), rats (Reeds et al., 1986), cattle (Dawson et al., 1988), and broilers (Morgan et al., 1989). There are also data which suggest that muscle protein synthesis may be enhanced in rats (Emery et al., 1984), lambs (Claeys et al., 1989), cattle (S. B. Smith et al., 1989), and swine (Bergen et al., 1989; Helferich et al., 1990). Chronic feeding of clenbuterol increased the rate of β-amino nitrogen uptake by 44 percent in the hindquarters of steers (Eisemann et al., 1988). This was caused by chronic elevation of blood flow with no difference in arterio-venous concentration. Plasma urea nitrogen concentrations were reduced 20 percent with chronic cimaterol treatment. These data are consistent with an increase in protein synthesis and deposition and reduced amino acid oxidation with chronic administration of clenbuterol. Although oxygen utilization by the hindquarters was also increased, glucose uptake was not, indicating greater reliance on lipid oxidation to support the expected increase in energy required for protein synthesis and deposition.

Attempts to use isolated muscle preparations have also yielded equivocal results. For example, using two muscle cell lines, L6 and G8-1, Harper et al. (1990) obtained an increase in protein synthesis of about 12 percent following treatment with cimaterol, with the half-maximal effect occurring at a concentration consistent with the binding of cimaterol to the β-receptor on the cells. The effect was blocked by the antagonist propranolol. As mentioned earlier, Kim and Sainz (1990) demonstrated a temporal reduction of the number of β-receptors in rat muscle with cimaterol treatment, which preceded a diminished response in muscle hypertrophy during a 14-day treatment period. These data are taken as indicative of the involvement of the β-receptor. The presence of the β-receptor on L6 myoblasts (Pittman and Molinoff, 1983) and in muscle suggests that the agonists do have a direct effect on the muscle, especially in light of the finding that treatment of animals with propranolol (a β-antagonist) can block the myogenic action of β-agonists (MacLennan and Edwards, 1989).

Young et al. (1990) observed a 25 percent increase in the quantity of myofibrillar protein and a 30 percent increase in the quantity of myosin heavy chain in primary muscle cell cultures of broiler chicks with 10^-7 M cimaterol. At higher levels of cimaterol the myosin heavy chain synthesis rate was increased 10 to 12 percent and protein degradation rate was decreased 10 to 15 percent. Clenbuterol (10^-7) increased fusion rate and protein synthesis rate in neonatal rat myoblast cultures but failed to exhibit similar effects in rat satellite cell cultures or cultures of L6 myoblasts and myotubes and had no effect on neonatal fibroblast cultures (McMillan et al., 1992). McElligott et al. (1989) also observed no effect on protein metabolism of L6 cells treated with the agonist zinterol. It appears that origin and/or presence of the full complement of regulatory factor genes (present in animal-derived cells) may be important in responsiveness of myogenic cells to the synthetic β-agonists.

Taking an overview of the literature, it would appear that the rate of muscle protein synthesis is increased and the protein degradation rate may be reduced in animals fed these synthetic β-agonists. Temporal patterns of change are present that make it difficult to ascertain which might be the major route by which β-agonists increase the rate of muscle protein deposition. Measurement of calcium-dependent proteinase, calpastatin, and cathepsin activities in skeletal muscle of β-agonist-treated sheep (Higgins et al., 1988; Wang and Beermann, 1988; Beermann et al., 1989; Kretchmar et al., 1990), cattle (Wheeler and Koohmaraie, 1992), rabbits (Forsberg et al., 1989), and broiler chickens (Morgan et al., 1989) indicate that activities of calpastatin are increased and/or the microcalpain protease activity is reduced with cimaterol, L-644,969, and L-665,871 adrenergic agonist administration in vivo. The protein-sparing effects of β-agonist administration have been demonstrated in response to restricted energy intake and starvation. Cimaterol converted a daily loss of 2.3 g carcass protein to a daily gain of 4.1 g carcass protein in lambs maintained at zero energy balance (Kim et al., 1989). Starvation-induced skeletal muscle atrophy was significantly reduced when clenbuterol was given to rats (Choo et al., 1990). Indications that clenbuterol-induced reduction in basal nitrogen loss could be achieved in sheep (Hovell et al., 1989) have subsequently been shown in further studies to be transient, and nitrogen loss was equal in control and treated sheep after a 4-day treatment period (Inkster et al., 1989).

Despite evidence for direct, receptor-mediated influences on skeletal muscle, it is possible that some of the changes in muscle protein metabolism in vivo are brought about by an indirect mechanism, that is, as a result of the changes in the circulating concentrations of some endogenous hormones (see review by Buttery and Dawson, 1987). Elevation of insulin concentrations have been observed in sheep (Beermann et al., 1986b; O'Connor et al., 1988) and cattle (M. Vestergaard, National Institute of Animal Science,

Front Matter (R1-R12)

Executive Summary (1-2)

1. Introduction (3-4)

2. Mechanisms of Action of Metabolic Modifiers (5-22)

3. Effect of Somatotropin on Nutrient Requirements of Dairy Cattle (23-29)

4. Effect of Metabolic Modifiers on Nutrient Requirements of Growing Ruminants (30-37)

5. Effect of Metabolic Modifiers on Nutrient Requirements of Growing Swine (38-51)

6. Effect of Metabolic Modifiers on Nutrient Requirements of Poultry (52-58)

References (59-73)

Authors (74-74)

Index (75-82)