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Metabolic Modifiers: Effects on the Nutrient Requirements of Food-Producing Animals
a 10-minute period every 90 minutes at stage of development coinciding with the nadir of basal and episodic endogenous cST secretion (8 weeks of age as reported by Vasilatos-Younkin and Zarkower, 1987) improved rate (P < 0.07) and efficiency (P < 0.01) of gain over a 21-day treatment regime of broiler-strain pullets. Modest reductions (P < 0.05 to 0.09) of indices of body lipid content were observed as compared to saline-treated controls. These changes in carcass fat content were not paralleled by a significant increase of carcass protein content. In contrast, continuous, nonepisodic infusion of cST impaired feed efficiency and had no influence on body fat indices. In several studies by other investigators, the continuous administration of cST resulted in an increase in carcass fat, with no change in growth rate (Cogburn et al., 1989b; Scanes et al., 1990). The significance of these studies is that age of birds and pattern of hormone administration are important considerations for obtaining positive responses to cST administration. In addition, if a pulsatile pattern of daily administration is required to obtain a positive response in birds, this introduces an additional complexity for the development of a delivery system for aves.
Qualitatively, avian species may appear less sensitive to, or a less likely target species for, exogenous ST treatment. However, the retardation of growth velocity and a shift toward excessive fat deposition is observed in broilers following hypophysectomy (King, 1969). Neutralization of circulating cST by passive immunization with cST antisera depressed growth velocity (Scanes et al., 1977). These studies indicate that cST is a factor influencing the physiology of nutrient partitioning; however, pharmacologic treatment of aves is at best equivocal.
Because cST exerts many of its growth and nutrient partitioning effects via IGF-I (Chapter 2), infusions or injections of this mediator have also been examined. Daily injections of 100 or 200 µg/kg body weight recombinant-derived human IGF-I, from 11 to 24 days of age, did not change the rate of gain, feed efficiency, body fat, or protein gain of broiler chicks (McGuiness and Cogburn, 1991). Likewise, the infusion of 100 µg/kg body weight/day of recombinant-derived human IGF-I did not affect rate of gain of a slow-growing brown layer strain; however, IGF-I infusion decreased abdominal body fat (Tixier-Boichard et al., 1992).
Hypothalamic Peptide Releasing Factors
Another strategy also affecting ST-mediated physiology involves the exogenous treatment of aves with hypothalamic peptides that stimulate endogenous ST secretion. These include thyrotropin-releasing hormone (TRH, a tripeptide) and ST-releasing factor (GRF, a 44-amino acid peptide). Both TRH (Harvey et al., 1978; Scanes and Harvey, 1981) and GRF (Leung and Taylor, 1983) have been shown to stimulate cST secretion both in vitro and in vivo.
Leung et al. (1984b) found that a daily intravenous injection of TRH at doses of 1 and 10 µg/day significantly improved rate of gain in 4-week-old broiler chicks. Over the 17-day treatment regimen, rate of gain was significantly increased by an average of 12 percent compared to saline-treated control birds. Serial blood sampling for circulating cST analysis indicated that the cST secretory response to TRH diminished with treatment duration. Based on these effects, the anabolic actions of TRH were attributed to the stimulation of ST secretion and the subsequent effect on metabolism. TRH effects on triiodothyronine (T3) and thyroxin (T4) production were discounted because thyroid hormone treatment, per se, depresses performance and cST secretion (Leung et al., 1984a). Ingestion of TRH at a level of 10 mg/kg diet from weeks 3 to 7 of production increased daily gain by 14 percent with improved feed conversion (Cogburn et al., 1989a); however, plasma cST concentrations decreased by 33 percent.
Bolus administration of human GRF at doses of 80 and 320 µg/kg body weight/day increased the rate of body weight gain slightly in 1-to 3-week-old broiler chicks (Baile et al., 1986). Circulating cST and IGF-I were increased significantly over control values; however, neither cST nor IGF-I revealed dose responsiveness. Continuous infusion of GRF had no effect on growth rate and induced pituitary desensitization. Leung (1986) reported that doses of 0.1 and 1 µg human GRF administered intravenously once a day transitorily increased rate of gain in 4-week-old broiler chicks. Over the 14-day treatment regimen, the initial 35 percent stimulation in growth rate observed on day 3 diminished to a 9 percent advantage as compared to control chicks. Such studies are consistent with the known physiological role of GRF, but they also indicate that refractoriness to the treatment could be anticipated with pharmacologic doses.
Phenethanolamine Derivatives
Various analogs of epinephrine have typical cardiac activity, but several have reported striated muscle activity selectively increasing the deposition rate of lean tissue (Chapter 2). Dalrymple et al. (1984) reported that clenbuterol added to the diet of broilers between 4 and 7 weeks of age improved rate (5.1 percent) and efficiency (5 percent) of body weight gain, increased dressed carcass weight (1.1 percent), and reduced body fat content (11 to 15 percent) when used at levels of 1 mg/kg diet compared to control broilers. Abdominal fat pad weight was selectively reduced (8.5 percent) in female broilers, while no effect was apparent in males. Comparative slaughter analysis revealed that nutrient partitioning was altered and the improved performance was the result of increased carcass protein (3.6 percent) and water (2.5 percent) content combined with reduced fat content primarily in females. Minimum effective dose determined from dose-response titration suggested