ability to promote skeletal muscle growth and reduce the fat content of animal carcasses. These orally active materials are usually referred to as β-agonists. Structures of some of the compounds that have been studied and for which effects have been reported in the literature are shown in Figure 2-3. These substances bind predominantly to β-receptors found in the membranes of cells. There are relatively few substances that bind almost exclusively to one type of receptor. Several of the agonists currently being evaluated for use as metabolic modifiers in the livestock industry show a marked specificity toward the β-2-receptor; stimulation of the β-1-receptor results in tachycardia. Transient increases in heart rate and systemic blood flow are observed with dietary administration of cimaterol in lambs (Beermann, 1987) and clenbuterol in cattle (Eisemann et al., 1988).

The β-adrenergic agonists reported in the literature as potential metabolic modifiers are all orally active, unlike ST and most of the anabolic steroids. Their main effects on the carcass are to increase skeletal muscle and reduce adipose tissue mass, with little or no effect on bone. This is sometimes accompanied by an increase in growth rate or feed efficiency. It is not surprising, then, that responses in live-weight gain and feed efficiency are related to the dose rate, with indications that efficacy is reduced at extremely high doses (Ricks et al., 1984; Hanrahan et al., 1986; Reeds et al., 1986). Effects on the overall body weight are of course markedly influenced by the relative changes in fat and muscle, which are in turn influenced by the dose. Mass of visceral tissues and most organs is not increased; in some cases liver mass is decreased. Therefore, percent of live weight present in the carcass is usually increased. All farm animal species tested (including poultry, ruminants, and pigs) show similar but variable effects (see Table 2-5).

In mammals the magnitude of the response generally appears to be greater in ruminants than in single-stomached animals, although a functioning rumen does not appear to be required in calves (Williams et al., 1987) or lambs (Williams et al., 1989). The 20 to 40 percent increases in skeletal muscle mass commonly observed in growing lambs and cattle are rarely observed in swine (see reviews by Hanrahan et al., 1987; Beermann, 1989, 1993; Anderson et al., 1991; Moloney et al., 1990). Likewise, the 20 to 40 percent reductions in adipose tissue mass observed in lambs and cattle are approximately half as large in pigs.

The magnitude of the influence of these compounds on the adipose tissue content of the carcass appears to be related to the tendency of the control animals to lay down fat (i.e., the magnitude of carcass or empty-body lipid accretion rate). Responses are less significant in preweaning and young rapidly growing animals, in which lipid accretion rates are low. Likewise, the enhancement of skeletal muscle growth is also less in these younger animals. Jones et al. (1985) and Moser et al. (1986) studied the impact of cimaterol dose on pigs treated from approximately 60 to 105

kg BW. Effects on average daily gain and feed efficiency were small, but dressing percentage was increased and carcasses contained up to 10 percent less fat and 10 percent more skeletal muscle in proportion to cimaterol dose. More recent studies with another compound, ractopamine, have demonstrated 5 to 20 percent improvements in growth performance and dose-dependent improvements in carcass composition, including 8 to 20 percent more muscle mass (Adeola et al., 1990; Watkins et al., 1990; Bark et al., 1992) and 4 to 37 percent less adipose tissue (Watkins et al., 1990; Bark et al., 1992). Although cimaterol was effective in finishing pigs, it had no effect on growth performance or carcass composition in younger pigs fed similar doses from 10 to 60 kg BW (Mersmann et al., 1987); nor were there any effects on the several indices of lipid metabolism studied. Similar differential responses between young and older animals have been observed in ruminants. The dose-response effects of cimaterol (Quirke et al., 1988) and L-644,969 (Moloney et al., 1990) on growth performance and carcass composition in finishing cattle exceed the magnitude of response seen in veal calves (Williams et al., 1987). Effects on skeletal muscle growth of 10-day-old lambs (15 kg BW) fed milk replacer and cimaterol for 21 days (Williams et al., 1989) was minimal (10 to 15 percent), approximately half the reduction in lipid accretion rate as that observed with similar treatment in older ruminating lambs from the same genetic pool (O'Connor et al., 1991).

The lack of response in very young ruminants and nonruminants may be related to fewer receptors, lower binding affinity, or more rapid development of refractoriness to these compounds. Kim and Sainz (1990) have shown that the number of β-receptors in rat plantaris muscles decreased 28 to 42 percent after 3 days of dietary cimaterol administration, which preceded the attenuation of the muscle hypertrophy response over a 14-day treatment period.

There have been relatively few specific breed or genotype comparison studies reported for effects of β-agonists in farm livestock. Either little evidence of important genotype-by-treatment interactions or none at all has been reported

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)