Metabolic Modifiers: Effects on the Nutrient Requirements of Food-Producing Animals (1994)

Rate and efficiency of nutrient use for growth are adversely affected when availability of essential nutrients (protein, vitamins, and minerals) and energy intake are not adequate. Nutrient requirements in growing ruminants have traditionally been empirically determined by altering diets or intake to define nutrient levels at which growth performance responses are maximized. Nutrient requirements are influenced by digestibility of feedstuffs, maintenance requirements, composition of gain, and metabolic processes that affect the efficiency of nutrient use. Energy and amino acid requirements for nonruminants can be estimated from known or measured rates of protein and amino acid deposition plus estimates of endogenous use (i.e., amino acid oxidation) for the whole body. When energy intake is adequate, whole-body protein accretion rates increase linearly with a stepwise increase in dietary protein intake until a plateau is achieved. That level of intake which produces the maximal response can be used as an estimate of the animal's requirement. The same principle applies for estimating energy intake requirements when protein intake is adequate. Excess energy intake results in increased lipid deposition, which causes decreased efficiency of feed conversion.

The complexity of the ruminant digestive system, particularly the contribution of the rumen microflora to nutrient absorption in the lower tract, makes it difficult to clearly define how well diets or diet formulations meet nutrient requirements in the growing animal. This complexity is responsible for the use of protein requirements for growing ruminants rather than use of individual amino acid requirements, as have been defined for nonruminants. The pattern of amino acids available for absorption in the small intestine can be predicted with reasonable accuracy in nonruminants. However, in ruminants, amino acids entering the small intestine come from rumen microbial protein, dietary protein that has escaped rumen fermentation, and endogenous secretions or contributions. Therefore, it is difficult to estimate both the quantity and profile of individual amino acids available for absorption from the small intestine of ruminants and the impact of amino acid nutriture on growth under normal management systems.

The effects of metabolic modifiers such as somatotropin (ST) and β-agonists on protein (amino acid) and energy use are primarily postabsorptive. Metabolic modifiers alter metabolism so that a greater proportion of absorbed nutrients is used for protein synthesis and deposition. Although ST, β-agonists, and anabolic steroids all improve rates of skeletal muscle growth, they differ in their metabolic effects on protein, lipid, and carbohydrate metabolism. They also differ in whether they increase organ and bone growth. This necessitates independent investigations into the effects of ST, β-agonists, and anabolic steroids on the nutrient requirements of growing ruminants. Information that defines mechanism(s) of action for each metabolic modifier is valuable in designing experiments or building models for predicting nutrient requirements in growing ruminants administered ST, growth hormone-releasing factor (GRF), a β-adrenergic agonist, or anabolic steroid implants. These mechanisms have been discussed in preceding chapters of this report. Only two recent reviews have addressed the issue of whether nutrient requirements are altered in livestock that have been administered metabolic modifiers (Boyd et al., 1991; Reeds and Mersmann, 1991). The effects of anabolic steroids in cattle were not addressed in these reports and a considerable amount of additional information has been produced since these reports were published. The objective of this chapter is to summarize what is known regarding the potential impact of the chronic administration of ST, GRF, select β-adrenergic agonists, or anabolic steroids on nutrient requirements of growing ruminants.

Effects of exogenous ST or GRF on nutrient requirements must be evaluated to determine whether feeding strategies should be changed to maximize response. Administration of GRF is an alternative approach to direct administration

of ST for elevating circulating levels of ST through stimulating endogenous ST secretion. It appears that the biology of ST effects on variables influencing nutrient requirements is similar in ruminants and swine, but data on nutrient requirements are limited for ruminants and more extensive for growing pigs (see Chapter 5).

Relative and absolute rates of energy and protein intake influence composition of gain. Therefore, effects of ST on energy or protein metabolism could influence nutrient requirements. Black and Griffiths (1975) clearly demonstrated relationships between energy and protein intake on nitrogen balance in untreated cross-bred lambs, ranging in weight from 3 to 38 kg and fed only milk to assess the tissue growth requirements independent of rumen microbial protein contributions. They observed that when nitrogen intake was inadequate, nitrogen balance was independent of energy intake but linearly related to absorbed nitrogen and metabolic body weight. When nitrogen intake was in excess of requirement, nitrogen balance increased linearly with metabolizable energy (ME) intake at a rate that decreased with increasing live weight. They also demonstrated that when nitrogen requirement was expressed per unit of energy intake, it was found to be constant for all lambs irrespective of live weight when intake was 55 kcal/kg⁷⁵ (near maintenance of body protein). As ME per unit metabolic body weight (BW⁷⁵) was increased above this level, nitrogen requirement per unit ME increased for lambs weighing less than 23 kg and decreased for heavier lambs. Determining the effects of ST on nutrient requirements of growing ruminants requires integration of these principles and estimating contributions of rumen microbial protein and volatile fatty acids to tissue amino acid and energy requirements.

The effects of exogenous administration of ST in growing ruminants have recently been summarized (Enright, 1989; Beermann and DeVol, 1991; McBride and Moseley, 1991; Moseley et al., 1992). Data from 21 trials with growing cattle indicate that with moderate doses of bST, average daily gain (ADG) is increased 10 to 15 percent and feed conversion efficiency is improved 9 to 20 percent, while carcass lean (muscle) content is increased 5 to 10 percent and carcass fat content is reduced 10 to 15 percent. These averages of responses are weighted toward greater emphasis on the longer-term studies in which growth performance of control animals has been shown to be not unusually low and represent summaries of data published as abstracts, in some instances. The responses to different doses of ST that reflect representative data for variation in initial weight, treatment time, frequency of administration, sex, breed, and diet are presented in Table 4-1.

The studies in which much larger increases in ADG or feed conversion efficiency were observed are those in which short-term administration periods of 8 to 21 days were utilized (Wolfrom and Ivy, 1985; Hancock and Preston, 1990) or those in which rates of gain of untreated cattle were less than 0.3 kg/day (Peters, 1986; Hancock and Preston, 1990). It is necessary to note that low ADG in the study by Peters was imposed as a restricted feed-intake aspect of the experimental design and that high doses of ST may impair weight gain because of the greater reduction of lipid accretion rate that occurs and associated effects on feed intake (Moseley et al., 1992).

Dose-response data that provide the needed information for assessing changes in nutrient requirements in growing cattle are limited. Nitrogen retention was increased and plasma urea nitrogen decreased in a dose-dependent manner in growing Holstein heifers administered 0, 6.7, 33, 67, 100, and 200 µg bST/kg live weight/day (Crooker et al., 1990). The maximum increase of 23 percent was observed at the highest dose, but the curvilinear relationship suggests that a dose between 50 and 100 µg/kg live weight achieves nearly maximal response. This is in agreement with data from dose-response studies with bST in lactating cows and porcine ST (pST) in growing pigs. Digestibility of dry matter and nitrogen were not affected by bST treatment.

More recent published results of dose-titration experiments in which recombinant bST was administered to finishing steers by injection (Moseley et al., 1992) or implant (Dalke et al., 1992) demonstrated a linear dose-dependent reduction in dry-matter intake and feed/gain. Carcass protein was increased and carcass lipid decreased without altering dressing percentage. Although high-concentrate diets with protein levels in excess of NRC requirements were fed, information was not available to indicate whether either energy or protein intake might have constrained the growth response, particularly at the highest doses administered. Addition of rumen escape protein (0.76 percent) did not enhance growth performance or carcass protein content in the implant study.

Summary of the data implies that dry-matter intake is decreased with ST administration in finishing cattle fed high-concentrate diets. Unfortunately, no definitive data are available for titration of energy or protein intake requirements in ST- or GRF-treated cattle. Results from at least three studies (Eisemann et al., 1986a,b; Peters, 1986) indicate that ST treatment of cattle fed slightly above maintenance levels of energy intake results in conservation of body protein or amino acids to support increases in nitrogen retention or carcass lean accretion. Eisemann et al. (1986a) observed significantly reduced leucine oxidation and a 6 percent increase in fractional protein synthesis rate in heifers administered ST for 14 days. Subsequently, Eisemann et al. (1989b) found that rates of radio labeled leucine incorporation into protein tended to increase and that whole-body rates of leucine oxidation were reduced in rapidly growing steers administered exogenous bST. Furthermore, it was

noted that bST increased (approximately 50 percent) the incremental efficiency of protein deposition. Total energy balance and total heat production were not altered by ST, indicating that gross efficiency of utilization of ME for gain was not changed (Eisemann et al., 1986b).

A small increase in net energy requirement is probable for maintenance in bST-treated cattle because significant increases in weights of the liver, kidneys, skeletal muscle, and bone have been observed, although heat production data do not support this. Increased efficiency of use of absorbed amino acids for protein gain may have been responsible for the significant increases in nitrogen retention or protein gain observed in these and other studies, the magnitude of which is less than that observed in growing and finishing pigs treated with similar doses of ST.

Direct comparisons of several protein intake levels at one or more doses of ST in cattle have not been reported. It would seem possible, and has been suggested (Crooker et al., 1990), that amino acid availability may have limited the response to exogenous ST in some studies. Evidence to support this is found in the demonstrated additive effects of abomasal casein infusion and daily bST administration on nitrogen retention in growing steers (Houseknecht et al., 1992) and lambs (Beermann et al., 1991) and in observed additive effects of fishmeal and ovine ST (oST) on feed conversion efficiency and hind leg muscle weights in growing lambs (Beermann et al., 1990).

The Net Carbohydrate and Protein System model developed by Fox and co-workers (Fox et al., 1992; Russell et al., 1992; Sniffen et al., 1992) was used to compare nutrient requirements of control and ST-treated steers in which nitrogen retention was increased 32.6 percent in the absence of abomasal casein infusion and increased an additional 44.6 percent with abomasal casein infusion (Fox et al., 1990a). After input of body weight, frame size, sex, condition, and breed designations, frame size was adjusted for bST-treated cattle to bring the predicted gain to equal observed gain. Predicted microbial protein production and amino acids

provided from feed were then used to predict protein gain and to compare these values with observed nitrogen retention. Predicted and observed values were in good agreement. Analysis with the model indicated that increased energy intake accounted for 5.8 percent of the response, change in composition of gain accounted for 8.1 percent, and increased efficiency of ME use accounted for 9.5 percent of the residual response. Although these are preliminary data from use of a model that has not been extensively validated, these results led to the conclusion that increased efficiency of use of absorbed amino acids for protein gain accounted for the other 75 percent of the increase in protein gain (nitrogen retention). These results would lead to the generalization that a diet balanced to meet amino acid requirements for large-frame (large mature size) cattle, as indicated by the NRC's 1984 requirements, would be adequate for support of the magnitude of response to bST observed in this study.

Few data are available to determine whether mineral requirements in growing cattle are altered with ST treatment. Eisemann et al. (1986a) found serum concentrations of calcium, phosphorus, and magnesium to be normal in bST-treated heifers. House et al. (1989) observed no change in copper, manganese, and zinc absorption in heifers treated with different amounts of bST; but retention of copper tended to increase with bST dose, and sulfur retention was increased about 30 percent at the highest dose.

Average daily gain is increased between 10 and 20 percent with daily administration of BSI (Wolfrom et al., 1985; Pullar et al., 1986; Johnsson et al., 1987; Pell and Bates, 1987; Zainur et al., 1989) or oST (Wagner and Veenhuizen, 1978; Wise et al., 1988; Beermann et al., 1990) in growing lambs. Feed intake was not significantly altered in most studies, and feed conversion efficiency was increased by 14 to 20 percent in at least four of the studies that reported significant increases in gain and composition of gain. Short-term (30 days) treatment of ram lambs with bST did alter composition without improving growth performance in one study (Rosemberg et al., 1989). Observed increases in carcass lean content ranged from 5 to 25 percent, although no change was observed in a few studies. Significant reductions in carcass or empty-body fat have been observed in nearly all studies. Gain, feed conversion efficiency, and composition changes all exhibited linear dose-response relationships in growing lambs administered 0, 50, 100, 150 or 250 µg bST/kg body weight/day (Zainur et al., 1989).

Few data are available to determine whether nutrient requirements are altered with ST treatment in growing lambs. Carcass protein accretion rate was increased 36 percent in cross-bred ewe and wether lambs administered 160 µg oST/kg live weight for 56 days without an increase in daily feed intake (Beermann et al., 1990). Lipid accretion rate was reduced 30.4 percent and ash accretion rate was increased 18 percent. As an indicator of skeletal muscle mass change, semitendinosus muscle weight was increased 18 percent. The relative increase in carcass or empty-body protein accretion rate observed in this study is approximately one-half that observed in growing pigs treated with similar doses of pST (see Chapter 5). One explanation may be that absolute amount or balance of individual amino acids available at the site of absorption may limit the response of growing lambs (and other ruminants) to ST treatment.

An attempt was made in the study by Beermann et al. (1990) to improve amino acid availability through addition of fishmeal to the diet in half the lambs receiving oST, human GRF (hGRF), or excipient. Replacement of an equal amount of soy protein with fishmeal protein (present at 4 percent of the diet) resulted in an additive effect with oST on feed conversion efficiency and proximal hind leg muscle weights (Beermann et al., 1990). ST improved feed: gain 20 percent, in addition to the 20 percent improvement achieved with fishmeal.

Results from recent studies with growing lambs (Beermann et al., 1991; MacRae et al., 1991) are in agreement with the results from similar studies with growing steers (Houseknecht et al., 1992), demonstrating that abomasal casein infusion and exogenous bST increase nitrogen balance in an independent and additive manner. Abomasal casein infusion (4 to 5 g/day) increased nitrogen balance 42 percent, and twice daily administration of 100 µg bST/kg body weight increased nitrogen balance 33 percent in wether lambs (28 kg body weight) fed a mixed concentrate diet at 85 percent of ad libitum intake (Beermann et al., 1991). The combined treatment increased nitrogen balance 89 percent. Administration of bST did not alter dry-matter or nitrogen digestibility; however, the efficiency with which lambs retained consumed nitrogen was increased. The percentage of consumed nitrogen that was retained was increased by bST from 23 to 31 percent when lambs received abomasal water infusions and from 27 to 34 percent when casein was infused into the abomasum. MacRae et al. (1991) observed no increase in nitrogen retention when nutrient infused sheep were administered ST at near nitrogen equilibrium, but a 25 percent increase was observed when nitrogen intake was increased. The percentage of infused nitrogen that was retained also increased with bST administration. These data agree with the apparent increase in efficiency with which consumed protein was deposited in the carcasses of lambs injected with oST (Beermann et al., 1990) and with similar results in growing pigs fed increments of protein in isocaloric diets (see Chapter 5). These data suggest that feeding strategies that provide adequate quantity and balance of amino acids may be needed to maximize the response to ST, despite the apparent improved efficiency with which amino acids are used for protein deposition. At this point, it can be speculated that if amino acid balance in the diet meets requirement profile, only minimum changes in nutrient

requirements for energy and protein would result with ST treatment. If intake is influenced by ST dose, nutrient density of diets may have to be increased to compensate. It remains to be demonstrated whether amino acid availability or balance (or both) limit the protein deposition response to ST in growing lambs and cattle fed conventional complete, mixed concentrate diets. Neither stepwise restriction of energy intake nor protein intake have been reported in lamb ST studies. Significant increases in weights of major organs such as liver, kidneys, and heart (Muir et al., 1983; Zainur et al., 1989; Beermann et al., 1990) indicate that small increases in maintenance requirement may be present. This increase is associated with proportional increases in organ and lean tissue weight, which resulted in more total lean tissue or protein mass per unit body weight. There is no apparent increase in maintenance requirement per unit of lean tissue in growing ruminants administered ST.

Limited data are available that describe long-term effects of GRF administration on growth and composition in growing cattle (Ringuet et al., 1988; Enright, 1989) and lambs (Wise et al., 1988; Byrem et al., 1989; Beermann et al. 1990). Multiple daily subcutaneous administrations of 5 µg hGRF/kg body weight increased average daily gain 13 percent and decreased feed: gain 18 percent in growing wether and ewe lambs treated for 6 or 8 weeks (Beermann et al., 1990). Doubling of the dose reduced feed intake 6 percent and resulted in no improvement in ADG. Carcass protein accretion rate was increased 30 to 35 percent, lipid accretion rate decreased 21 to 28 percent, and ash accretion rate increased 30 percent. Lambs in this study were fed a diet containing 16 percent crude protein and adequate energy. Subcutaneous infusion of a hGRF analog into lambs for 28 days increased rate of gain 16 percent and improved feed conversion 18 percent without effect on feed intake, wool growth, or carcass weights (Godfredson et al., 1990). Treated lambs contained less fat. A similar response was obtained with subcutaneous infusion of hGRF in wether lambs for 5 weeks (Byrem et al., 1989). Because the data indicate that responses nearly equal those achieved with ST administration, similar conclusions must be drawn for effects on nutrient requirements in lambs.

Effects of GRF on energy and nitrogen metabolism were recently investigated in growing beef steers fed a 75 percent concentrate diet at two levels of intake for 3 weeks (Lapierre et al., 1992). GRF treatment increased nitrogen retention 108 and 80 percent at the low (approximately 88 g/day) and high (approximately 159 g/day) levels of nitrogen intake. A significant increase in digestibility was observed, but most of the improvement resulted from reduction in nitrogen excretion and from the significant (approximately 50 percent) increase in efficiency of nitrogen utilization that was observed at both levels of intake. Measurements of energy and nitrogen metabolism in the portal drained viscera and liver in these steers demonstrated reduced amino acid extraction ratio and reduced net uptake of amino acids by the liver (Reynolds et al., 1992). GRF decreased the amount of energy lost in the urine and feces, but this was countered by increased heat production. Total tissue energy retention was not altered, but energy retained was repartitioned toward 67 and 19 percent less body lipid at the low and high intakes, respectively. The authors concluded, based on calculations, that maintenance energy costs and the efficiency of ME use for tissue deposition were not altered by GRF.

Taken together, results from recent studies suggest that protein (amino acid) availability and amino acid profile may be important factors influencing the magnitude of protein deposition response to ST or GRF administration in growing ruminants. The large absolute increases in protein synthesis and deposition rates observed in ST-or GRF-treated animals have occurred when protein nutriture was considered in the design of the experiment. Enhancing amino acid availability enhances the protein deposition response, and the expected increase in dietary protein or amino acid requirement is offset by increased efficiency of nitrogen utilization. Houseknecht and Bauman (1992) used data from five separate studies to calculate the biological value of consumed protein (grams of nitrogen retained per gram of nitrogen absorbed) in cattle or lambs treated with ST or GRF. The biological value was increased by 20 percent to as much as 70 percent in treated animals. This increased biological value appears to result from reduced amino acid oxidation and a major site of reduction appears to be the liver. Carefully designed studies will be required to elaborate the integrated effects of species, stage of growth, genotype and gender, and dose of ST or GRF on nutrient requirements of growing ruminants.

Well-designed experimental approaches to address the question of whether nutrient requirements are altered with exogenous ST administration in cattle, lambs, or other ruminants need to be conducted before meaningful recommendations can be made. Dose-response relationships between growth performance and composition of empty-body gain have not been comprehensively evaluated to determine influences of genotype, gender, and stage of growth. Data from several studies suggest that the smaller protein accretion rate and nitrogen balance responses observed in ruminants administered ST or GRF, compared with responses in swine, are caused by constraints on quantity or balance of amino acids available at the site of absorption. However, ST or GRF administration in ruminants effectively increases the calculated biological value (gram of retained nitrogen

per gram of absorbed nitrogen) of consumed proteins. This appears to be the result of direct effects on the liver to decrease the extraction ratio and net removal of amino acids from the circulation (an amino acid sparing effect). It is not currently possible to define requirements or formulate diets that deliver the appropriate balance and quantity of amino acids to match the increase in protein accretion rate in ruminants, as can be done for nonruminants. Quantity and balance of amino acids exiting the rumen are not easily predicted or determined because of the alterations that occur during rumen fermentation. The magnitude of protein accretion rate and decrease in lipid accretion rate are also influenced by dietary energy levels, gender, age, and breed of cattle and sheep. To allow for nutrient adequacy assessment, future studies must include careful consideration and detailed description of diets and animals used. Ultimately, studies designed to assess protein and energy requirements using empty-body protein (amino acid), lipid, and mineral accretion rates as response variables must be conducted to accurately and adequately define nutrient requirements in growing ruminants. Because the mechanism(s) by which ST alters growth performance and composition of gain appear to be similar in growing ruminants and pigs (Chapter 2), dietary manipulations for use of ST in ruminants should be based on the responses to alterations that have been demonstrated for growing pigs treated with pST (Chapter 5).

There are relatively few data on which to base sound conclusions or predictions of the nutrient requirements of growing ruminants receiving β-adrenergic agonists. Systematic investigations into the protein and energy requirements of growing or finishing cattle or sheep have not been conducted. These important data are also limited for swine (Chapter 5) and poultry (Chapter 6). Defining these requirements requires (1) applying current knowledge regarding mechanism of action, growth performance, and composition of gain results determined over a range of protein intake when energy is not limiting and (2) determining whether altering the balance of available amino acids influences the efficacy of the β-adrenergic agonists for their effects on protein deposition rate. A detailed discussion of the biological basis of amino acid and energy requirements in growing animals has recently been published (Reeds and Mersmann, 1991) in which the authors also address the important issues regarding assessment of nutrient requirements in animals fed β-adrenergic agonists. Use of a wide range of protein intakes and the break-point analysis, which has been employed to define the nutrient requirements of swine receiving pST (Chapter 5), has likewise been applied to growing swine fed β-agonists (Dunshea, 1991). Although appropriate, studies designed to investigate the effects of postruminal protein infusion on protein deposition response in ruminants fed β-agonists have not been reported.

Extrapolation from results of ST studies in growing ruminants to the β-agonist-treated ruminant is logical and may be appropriate, with one exception: the significant increase in weight of the liver and kidneys caused by ST treatment is not observed with β-agonist administration, although increased energy expenditure has been observed [see reviews by Reeds and Mersmann (1991) and Beermann (1993)]. As is the case for administration of ST, composition of gain and tissue requirements of gain must be known across the range of genotypes, stages of growth, gender, and dose when feedlot diets are used for cattle and lambs. These are not currently available. Also, the quantity and balance of amino acids provided by rumen fermentation must be understood and accurately predicted across a wide range of diet formulations currently used in commercial beef and lamb production before diet alterations can be recommended. Although models are being developed, these models must first be validated for the range of commercial situations to which they will be applied.

Another important consideration for defining nutrient requirements in ruminants fed β-adrenergic agonists that alter composition is that they do not chronically alter feed intake, as is the case with ST administration to lactating dairy cattle (increase) or finishing steers (decrease). In most studies, feed intake is not altered, although rate and efficiency of gain are improved, albeit in a transient manner in some instances (Beermann et al., 1986a; see reviews by Boyd et al., 1991; Beermann, 1993).

The efficiency with which energy and protein are used for protein accretion declines with increasing age or weight of the growing ruminant (Black and Griffiths, 1975) and is influenced by sex, genotype, and environmental differences. Dietary modifications used to study these effects in growing lambs administered ST or GRF have also been investigated using β-adrenergic agonists. Addition of fishmeal to the diet of lambs treated with oST improved feed conversion efficiency in an additive manner with ST when compared with the conventional diet containing soy protein as the predominant protein source (Beermann et al., 1990). Similar effects on feed efficiency were not observed in growing-finishing lambs fed cimaterol (Beermann et al., 1986a). However, fishmeal increased the weight of individual skeletal muscles in the hind leg by 15 to 19 percent over a 10-week growing period and the effects were additive with the 20 percent increase caused by cimaterol. Hind leg muscles from lambs that received both fishmeal and cimaterol were 40 to 45 percent heavier than the same muscles in lambs that received neither. These data suggest that providing adequate quantity and/or quality of absorbed nitrogen may also be important prerequisites to achieving maximum response with β-agonists in ruminants.

Experiments must be conducted to establish the relationships between levels of dietary protein and energy intake in growing ruminants fed β-adrenergic agonists to empirically determine nutrient requirements. It cannot be assumed that the increased efficiency of protein use for muscle growth that is observed in lambs (Beermann et al., 1991) and steers (Houseknecht et al., 1992) treated with bST will be observed in ruminants fed β-agonists. Detailed characterization of diet formulations and factors that influence nutrient requirements must accompany the composition-of-gain data obtained across the potential application dose of the individual β-agonist being investigated. Until these studies have been completed, diets for ruminants should be formulated to take into account the energy requirements associated with increasing empty-body or carcass protein accretion to the magnitude expected with administration of the β-agonist. Whether additional nonprotein energy should be fed to these animals remains an open question.

Mineral requirements are not expected to be altered because neither bone mass nor length is altered in ruminants administered β-agonists (Beermann, 1993). Impact of environmental fluctuations on nutrient requirements of growing ruminants have not been evaluated but may be important (Fox et al., 1988). The Food and Drug Administration has not approved any of the β-adrenergic agonists for use in growing or finishing ruminants.

Larger increases in carcass protein deposition and skeletal muscle growth have been observed in growing cattle and lambs fed select β-agonists than have been observed with ST or GRF administration, without obvious differences in diets. Furthermore, visceral organ weights are not increased with β-agonists, suggesting that conservation of amino acids may occur and an altered pattern of dietary amino acids may be required for optimizing protein deposition with β-agonists as compared with ST or GRF. The question of whether β-agonists improve efficiency of protein utilization for protein deposition in growing ruminants, as has been demonstrated for ST and GRF, is unresolved. Although efficiency of energy use is unaltered, whether energy intake requirements are altered is also unknown. Systematic evaluation of energy and protein (amino acid) requirements in ruminants fed β-agonists must be conducted before meaningful conclusions can be drawn and accurate predictions can be made.

The same considerations given for determining effects of ST, GRF, or β-adrenergic agonists on nutrient requirements in growing ruminants must be extended to administration of anabolic steroid implants. Significant limitations exist in the data from lamb and cattle experiments in which nutritional manipulations were conducted. Either titration of energy or protein requirements involved too few intervals, or accurate determination of composition of gain was not conducted. It appears that anabolic steroids increase feed intake and increase the live weight at which a similar physiological maturity (percent body fat) is reached (Perry et al., 1991). Special diet formulations have not been required to achieve significant improvement in rates of gain or feed efficiency in growing ruminants implanted with anabolic steroids.

Preston and Burroughs (1958) demonstrated that diethylstilbestrol-treated lambs achieved the greatest improvement (32 percent) and absolute average daily gain when fed a high-energy diet containing 17 percent crude protein, compared to 13 and 9 percent crude protein diets. Feed conversion efficiency was also maximized with this diet, compared to other protein and lower energy combinations, but the lack of a plateau among protein levels suggests that nutrient adequacy was not unequivocally demonstrated. Variability in carcass composition also existed among the treatment groups. Although dressing percentage and rib eye area may be consistently increased by trenbolone acetate-estradiol implants (Bartle et al., 1992), carcass measurements of fat thickness, percentage kidney and pelvic fat, and longissimus (rib eye) area are insufficient indices of composition of gain to assess the question of altered nutrient requirements in ruminants treated with anabolic steroids.

Significant improvement in empty-body weight gain was observed in very young (119 kg live weight) British Friesian steers fed a silage diet substituted with increasing concentrations of fishmeal (0, 50, 100, and 150 g/kg diet) (Gill et al., 1987). Estradiol-17β implants increased daily gain, but only when fishmeal was supplemented in the silage diet (13.75 percent crude protein) at 100 or 150 g/kg diet. The interaction was significant and was associated with increased dry-matter intake in implanted steers (gain was 0.77 kg/day with silage alone). Fishmeal increased empty-body and carcass protein, and the effects appeared to be additive with the estradiol implantation. Fat content was not altered with estradiol implants or with fishmeal. These data suggest that improved balance of nutrients may be required to facilitate growth potential and response to anabolic steroids, if nutrients are limiting. Similar relationships were observed in fattening steers and heifers fed a silage diet with or without fishmeal (Lowman and Neilson, 1985).

Estimates of the effects of anabolic steroids on maintenance indicate there is little change. Lobley et al. (1985) observed no increase in heat production in steers administered a combined trenbolone acetate-estradiol implant that dramatically increased live weight gain and nitrogen retention. Lemieux et al. (1988) and Solis et al. (1989) reported that estimates of net energy for maintenance were decreased by only 1 to 3 percent in implanted cattle. They also reported

that estimates of net energy for gain are reduced 14 to 20 percent with anabolic steroids in cattle. These estimates reflect the shift in the proportion of absorbed nutrients used for protein deposition versus lipid accretion as well as partial efficiency differences in gain of lean versus fat.

Significant increases in ADG (up to 23 percent) have been observed in cattle fed conventional high-concentrate diets and implanted with combinations of anabolic steroids. Increase in dry-matter intake appears to account for a large portion of this response. Maintenance requirements are not increased and adequate data are not available to determine whether nutrient requirements of growing ruminants administered anabolic steroids are different from those found in NRC publications. Published results suggest that enhancing amino acid availability and/or pattern of absorbed amino acids will improve protein deposition rates in growing cattle. Achieving maximum protein deposition rates with anabolic steroid implants may necessitate developing strategies to remove the constraint suggested above. Considerable additional research is required to determine the importance of nutrient balance, particularly amino acid availability and balance, in supporting greater protein accretion rates in ruminants treated with anabolic steroids. Assessment is complicated by the lack of control we now have over the profile and amount of amino acids provided by the rumen that are also available for supporting protein accretion. Studies conducted and published in the future must include detailed descriptions of the diets used to allow nutrient adequacy assessment. In addition, studies specifically designed to assess protein and energy requirements of growing ruminants administered anabolic steroids must be conducted using empty-body and/or carcass protein accretion rates as response variables to accurately and adequately achieve these objectives.