chronic bST treatment, feed intake increases; this is associated with a gradual adjustment in lipogenesis that enables the cow to replenish body reserves over the lactation cycle.

It is important to understand that the biological effects of ST are chronic rather than acute. The effects of ST are not observed in short-term (2 hour) incubations with adipose tissue but only become apparent after 24 hours (Walton and Etherton, 1986, 1987; Walton et al., 1986). This suggests that ST acts to inhibit nutrient utilization in adipose tissue by changing the mass of glucose transporter proteins and/or key lipogenic enzymes either by transcriptional or post-transcriptional regulation. Recent evidence provides support for this hypothesis. Mildner and Clarke (1991) have shown that pST decreases fatty acid synthase mRNA levels by 75 percent in pig adipose tissue. Furthermore, when pigs are treated with pST for 7 days, there is a 20 to 40 percent decrease in glucose transporter (GLUT4) mRNA levels in adipose tissue and an associated 40 percent decrease in GLUT4 protein (Etherton and Louveau, 1992). Other studies also have shown that ST decreases acetyl CoA carboxylase activity in cultured sheep adipose tissue (Vernon et al., 1991) and that in vivo ST treatment of lactating cows (Lanna et al., 1992) and pigs (Harris et al., 1990; Liu et al., 1991) reduces enzyme activity. The fact that ST reduces acetyl CoA carboxylase, fatty acid synthase, and GLUT4 mRNA abundance in adipose suggests that ST affects lipid metabolism by altering transcription of these key metabolic genes. Because insulin sensitivity of adipose tissue is reduced and these genes are insulin regulated, it appears that ST acts, in part, by impeding the insulin signal pathway(s), which results in a diminution in transcription of insulin-regulated genes. This insulin antagonistic effect of ST, however, does not appear to universally affect all insulin-regulated genes, since some of the effects (i.e., antilipolytic) of insulin are not reduced by ST (Sechen et al., 1989a, 1990).

During the past 10 years there has been a remarkable increase in our understanding of the physiological effects that ST exerts on adipose tissue of domestic animals. Despite this, little is known about the ST intracellular signal pathway(s) that cause these alterations in lipid metabolism. Furthermore, it remains unclear how the metabolic changes that occur in adipose tissue in response to ST are coordinated with those that take place in the liver, muscle, mammary tissue, and other tissues to effect the remarkable increases in production observed.

ST has numerous effects on carbohydrate metabolism (see Table 2-4). This is of particular importance in the dairy cow, in which glucose originates from gluconeogenesis and typically 60 to 85 percent of the glucose turnover is used for milk synthesis. Treatment of cows with bST increases glucose ILR and reduces whole-body glucose oxidation (Bauman et al., 1988). The increase in glucose ILR is the result of an increase in hepatic gluconeogenesis (Pocius and Herbein, 1986; Cohick et al., 1989; Knapp et al., 1992) and one of the tissues that reduces its use of glucose is the hind limb muscle (McDowell et al., 1987). Adaptations in glucose production and oxidation in bST-treated cows are quantitatively equal to the extra glucose required for the increased milk synthesis (Bauman et al., 1988). In pigs (in the postabsorptive state) treated with pST, there is also an increase in hepatic output of glucose (Gopinath and Etherton, 1989b). In both cattle and pigs, liver responses to insulin are decreased (Boisclair et al., 1989a; Gopinath and Etherton, 1989b). In bST-treated lactating cows this is particularly important because the liver is the predominant source of glucose for milk synthesis, and insulin acts to inhibit hepatic production of glucose. Thus, the reduction in hepatic response to insulin allows the liver to sustain the increased rate of gluconeogenesis that is critical to support the increase in milk synthesis.

When pigs are treated chronically with pST, plasma glucose and insulin concentrations are elevated (Gopinath and Etherton, 1989a; Dunshea et al., 1992a). The increase in plasma glucose is most likely related to a reduction in glucose uptake, particularly by adipose tissue. Because a significant quantity of glucose is metabolized in adipose tissue of pigs, a decrease in glucose utilization by adipose tissue redirects a considerable quantity of glucose to other tissues. For example, it has been shown that approximately 40 percent of whole-body glucose uptake measured in the basal state and 25 to 30 percent measured in the insulin-stimulated state are used by adipose tissue of barrows (Dunshea et al., 1992c). In contrast, glucose utilization by adipose tissue of pST-treated pigs amounts to only about 7 percent of whole-body glucose turnover (Dunshea et al., 1992c).

Less is known about the effects of ST on protein metabolism than about either lipid or carbohydrate metabolism. It is clear the ST treatment increases muscle protein deposition in growing animals and milk protein secretion in lactating cows. No studies have examined the effects of ST on the kinetics of protein metabolism during ST treatment in dairy cows. In growing pigs and cattle, one of the most characteristic responses to ST treatment is a dose-dependent decrease in blood urea nitrogen concentration. This suggests that whole-body oxidation of amino acids and the concomitant hepatic conversion of ammonia to urea are reduced. These adaptations in amino acid metabolism are consistent with an increased use of amino acids for protein accretion.

The kinetics of amino acid metabolism have been examined in growing cattle treated with bST. Eisemann et al. (1986a,b) have reported that ST treatment of beef heifers fed slightly more than maintenance amount increased nitrogen

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)