J. P. McMurtry

Effect of exogenous chicken growth hormone (cGH) administration on insulin-like growth factor-I (IGF-I) gene expression in domestic fowl

The effects of chicken growth hormone (cGH) infusion on insulin-like growth factor (IGF-I) gene expression in rapidly-growing, meat-type chickens was investigated. Chicken GH was infused either continuously or in a pulsatile fashion to 8-week-old birds during a 7-day period. Following cGH infusion, both IGF-I peptide and IGF-I mRNA content were measured in selected tissues. Steady-state IGF-I mRNA abundance was determined by a solution hybridization nuclease protection assay using total cellular RNA obtained from liver, heart, kidney, spleen, epiphyseal growth plate cartilage, gastrocnemius and pectoralis muscles. Continuous infusion of cGH elicited a two-fold increase in IGF-I peptide concentration in the kidney (P < 0.05), while all other tissues remained unchanged by cGH treatment under this infusion pattern. Pulsatile cGH infusion produced a two-fold increase in IGF-I peptide content in the liver, gastrocnemius, and pectoralis muscles (P < 0.05). In contrast with the levels of IGI-I peptide, relative steady-state IGF-I mRNA content was two-fold higher in liver and spleen of birds treated continuously with cGH, but was decreased to 35 and 55% of control birds in heart and pectoralis muscle. Pulsatile cGH infusion resulted in a 64% increase in IGF-I mRNA in the liver and remained unchanged in other tissues. Under both patterns of administration, changes in IGF-I mRNA were not reflected by changes in tissue IGF-I peptide levels. Overall correlations between tissue IGF-I mRNA and peptide levels were low and not significant in the tissues studied, except for liver under pulsatile infusion, in which IGF-I peptide levels paralleled changes in IGF-I mRNA. We conclude that, in chickens, exogenous cGH treatment stimulates hepatic IGF-I transcription and translation only when the pattern of infusion mimics the natural episodic pattern of GH secretion. The low correlation between IGF-I peptide and mRNA levels in extra-hepatic tissues may indicate differential responsiveness to GH in birds, and that in some tissues IGF-I levels are under GH-independent transcriptional controls.

Effect of early feed restriction in male broiler chicks on plasma metabolic hormones during feed restriction and accelerated growth

1. Plasma GH was greater (P less than 0.05) on day 12 in ad libitum-fed birds compared to restricted chicks. Conversely, maximum GH levels were found to occur in the nutrient restricted chicks during the period of accelerated growth (day 42). 2. A significant decline in circulating insulin concentrations with advancing age was evident in both ad libitum-fed and restricted chicks. 3. Feed restriction significantly suppressed circulating T3 in restricted chicks, with concentrations returning to control levels upon refeeding. 4. A significant increase in T4 with advancing age was evident in both treatment groups, with T4 being significantly greater in controls compared to restricted chicks at 54 days of age.

New insights into the mechanism and actions of growth hormone (GH) in poultry

Despite well documented anabolic effects of GH in mammals, a clear demonstration of such responses in domestic poultry is lacking. Recently, comprehensive dose-response studies of GH have been conducted in broilers during late post-hatch development (8 to 9 weeks of age). GH reduced feed intake (FI) and body weight gain in a dose-dependent manner, whereas birds pair-fed to the level of voluntary FI of GH-infused birds did not differ from controls. The reduction in voluntary FI may involve centrally mediated mechanisms, as hypothalamic neuropeptide Y protein and mRNA were reduced with GH, coincident with the maximal depression in FI. Growth of breast muscle was also reduced in a dose-dependent manner. Circulating IGF-I was not enhanced by GH, despite evidence that early events in the GH signaling pathway were intact. A GH dose-dependent increase in circulating 3,3,5-triiodothyronine(T3) paralleled decreases in hepatic 5D-III monodeiodinase activity, whereas 5D-I activity was not altered. This confirms that a marked hyperthyroid response to GH occurs in late posthatch chickens, resulting from a decrease in the degradative pathway of T3 metabolism. This secondary hyperthyroidism would account for the decreased skeletal muscle mass (52) and lack of enhanced IGF-I (53) in GH-treated birds. Based upon these studies, it is now evident that GH does in fact have significant effects in poultry, but metabolic responses may confound the anabolic potential of the hormone.

Effects of growth hormone and pair-feeding on leptin mRNA expression in liver and adipose tissue

Previous research has reported that elevations in circulating growth hormone (GH) levels in meat-type chickens depresses feed intake (FI) more than 30%. It is known that the product of the obese gene, leptin, functions to regulate FI and energy expenditure. To investigate the effect of GH on leptin gene expression, broiler chickens were infused with recombinant chicken GH. To separate any secondary effects of a GH-induced reduction in FI on leptin expression, groups of birds were pair-fed to an average level of voluntary intake similar to GH-treated birds, but received no GH treatment. GH treatment induced a dose-dependent increase in liver leptin gene expression, as measured by reverse transcriptase-polymerase chain reaction, whereas leptin expression in adipose tissue was unchanged. Conversely, in chickens pair-fed (feed-restricted) there was a decrease in leptin gene expression in both tissues. These results provide evidence of a direct effect of GH on leptin gene expression, which is independent of any effects on intake attributable to GH-treatment, and suggest differential regulation of leptin expression between adipose tissue and liver. The results of these experiments provide the first evidence of a relationship between GH and leptin in domestic birds.

Digestible lysine requirements of male broilers from 28 to 42 days of age.

Research addressing digestible Lys requirement data of modern broilers from 4 to 6 wk of age is limited. Male broilers (1,632 Ross×Ross TP16 and 3,000 Cobb×Cobb 700) were used in separate experiments to determine the digestible Lys requirements from 28 to 42 d. In each experiment, 2 diets (dilution and summit) consisting of corn, soybean meal, animal protein meal, and peanut meal were formulated to be adequate in all other amino acids. The dilution and summit diets were blended to create 9 titration diets. A control diet formulated to contain corn, soybean meal, and animal protein meal as the primary ingredients was used for comparison with the titration diets. Body weight gain, feed intake, digestible Lys intake, digestible Lys intake:BW gain, feed conversion, mortality, carcass yields, and physiological measurements were assessed during experimentation. Digestible Lys requirements were estimated using a quadratic broken-line model. In experiment 1, the digestible Lys requirement for male Ross×Ross TP16 broilers was determined at 0.988, 1.053, 0.939, and 0.962%, respectively, for BW gain, feed conversion, carcass weight, and total breast meat weight. In experiment 2, the digestible Lys requirement for male Cobb×Cobb 700 broilers ranged from 0.965, 1.012, 1.029, 0.987, and 0.981%, respectively, for 28- to 42-d BW gain, feed conversion, carcass weight, total breast meat weight, and total breast meat yield. Digestible Lys requirements for male Ross×Ross TP16 and Cobb×Cobb 700 broilers were estimated at 1.001 and 0.995%, respectively, based upon averages of live performance and meat yield responses. Both strains required the highest requirement estimate of digestible Lys to optimize feed conversion.

An Examination of the Role of Feeding Regimens in Regulating Metabolism During the Broiler Breeder Grower Period. 2. Plasma Hormones and Metabolites

A trial was conducted to determine the effects of different feeding regimens on plasma hormone and metabolite levels in 16-wk-old broiler breeder pullets. A flock of 350 Cobb 500 breeder pullets was divided in 2 at 28 d of age and fed either every day (ED, 5 pens of 35 birds) or skip-a-day (SKIP, 5 pens of 35 birds) from 28 to 112 d of age. Total feed intake did not differ between the 2 groups. At 112 d, 52 randomly selected pullets from the larger flock of ED-fed pullets, and 76 from the SKIP-fed pullets were individually caged and fed a meal of 74 g (ED) or 148 g (SKIP). Blood samples were collected from 4 pullets in each group by cardiac puncture at intervals after feeding. Plasma was analyzed for insulin, glucagon, insulin-like growth factor-I and insulin-like growth factor-II, triiodothyronine and thyroxine, corticosterone, leptin, glucose, nonesterified fatty acids, triglycerides, and uric acid. Feed retention in the crop was also noted at each interval. In ED birds, the crop was empty by 12 h and in SKIP birds, the crop was empty by 24 h after feeding. The physiological responses to fasting, such as increased glucagon and corticosterone and reduced plasma triglyceride, occurred at times coincidental with crop emptying in both ED and SKIP birds. Overall, mean insulin-like growth factor-I levels were higher (P < 0.05) in ED birds. Triiodothyronine was higher (P = 0.09) in SKIP birds. Overall mean plasma corticosterone was 2-fold higher in SKIP-fed birds, which may be related to the increased length of fasting periods, hunger, and stress. Plasma leptin was consistently higher in ED-fed birds, which was indicative of their more consistent food supply and more stable energy status. In summary, the experiment reported here shows that different feeding regimens can alter hormone and metabolite profiles, in spite of total feed intakes being equal.

Effect of pulsatile or continuous administration of pituitary-derived chicken growth hormone (p-cGH) on lipid metabolism in broiler pullets.

1. The effects of pulsatile and continuous intravenous administration of exogenous, pituitary-derived chicken growth hormone (p-cGH) on lipid metabolism and endocrine/metabolite levels of broiler-strain pullets were studied. 2. Eight-week-old pullets were administered p-cGH or vehicle over a 10 min period every 90 min for 7 days. 3. Pullets were also administered the same daily amount (123 micrograms/kg of body weight/day) continuously for 7 days. 4. Feed intake, body weight gain, in vitro lipogenesis and hepatic enzyme activities were determined with certain hormones identified with the control of growth. 5. Pulsatile p-cGH administration for 7 days lacked effect on weight gain, feed efficiency, muscle or bone development. 6. Abdominal fat pad size was decreased (P less than 0.05) by pulsatile but not continuous administration of p-cGH. Pulsatile p-cGH administration also decreased (P less than 0.05) in vitro lipogenesis. Liver malic enzyme and isocitrate dehydrogenase activities were increased (P less than 0.05) by pulsatile but not continuous administration of p-cGH. In contrast, glutamic oxaloacetic transaminase activity was increased by a continuous infusion of p-cGH. 7. Plasma concentrations of T4 corticosterone and triglycerides were decreased (P less than 0.05) by a pulsatile but not a constant infusion of p-cGH. 8. Plasma T3 and GH were increased (P less than 0.05) by pulsatile p-cGH compared to both a continuous infusion of p-cGH and the saline controls. 9. This study is the first to prove that in the broiler chicken, the pattern of exogenous p-cGH administration is a factor influencing in vitro responses to the hormone.

Influence of early plane of nutrition on enzyme systems and subsequent tissue deposition

The occurrence of compensatory growth is of great significance because of its potential effects on body composition (muscle versus adipose development) at maturity. Studies have been conducted with chickens in which feed intake is limited to meet their maintenance energy requirements for 6-d period, beginning 6-d post-hatch. Following realimentation, the birds undergo compensatory growth that results in a greater proportion of lean versus adipose tissue at 8 wk of age compared to birds given ad libitum access to feed. During energy restriction, hepatic enzyme activity associated with lipogenesis and in vitro lipogenesis were suppressed, followed by an over-shoot at realimentation, and a subsequent suppression in activity during compensatory growth. The concentrations of metabolic hormones were not effected by nutrient restriction. Early post-hatch feed restriction was found to delay the proliferation of adipocytes but did not affect the development of normal adipocyte size. In summary, early feed restriction of short duration in chickens induces permanent changes in the mechanisms responsible for adipose tissue development.

CHICKEN HEPATIC METABOLISM IN VITRO. PROTEIN AND ENERGY RELATIONS IN THE BROILER CHICKEN--VI. EFFECT OF DIETARY PROTEIN AND ENERGY RESTRICTIONS ON IN VITRO CARBOHYDRATE AND LIPID METABOLISM AND METABOLIC HORMONE PROFILES*

1. Ross male broiler chicks growing from 14 to 28 days of age were fed 14 and 20% protein diets (4 kcal day-1/body wt0.66) or 20 and 28% protein diets (2.8 kcal day-1/body wt0.66) in a 2 x 2 factorial arrangement to determine the effects of protein and energy intakes on in vitro lipogenesis (IVL) and net glucose production (NGP). Plasma concentrations of insulin, glucagon, thyroid hormones (T3 and T4) and somatomedin-C (Sm-C) were estimated by radioimmunoassay. 2. There was a significant (P less than 0.05) decrease in IVL in the chicks given the higher daily protein intake. 3. The higher protein intake increased (P less than 0.05) NGP while the lower energy intake decreased (P less than 0.05) NGP. 4. Insulin, both thyroid hormones and Sm-C were affected by dietary energy and protein intakes.

In vitro lipid metabolism, growth and metabolic hormone concentrations in hyperthyroid chickens

Indian River male broiler chickens growing from 7 to 28 d of age were fed on diets containing energy:protein values varying from 43 to 106 MJ/kg protein and containing 0 or 1 mg triiodothyronine (T3)/kg diet to study effects on growth, metabolic hormone concentrations and in vitro lipogenesis. In vitro lipid synthesis was determined in liver explants in the presence and absence of ouabain (Na+, K(+)-transporting ATPase (EC 3.6.1.37) inhibitor) to estimate the role of enzyme activity in explants synthesizing lipid. Growth and feed consumption increased (P < 0.01) when the energy:protein value decreased from 106 to 71 MJ/kg protein; however, both variables decreased as the value was further decreased from 53 to 43 MJ/kg protein. Triiodothyronine depressed (P < 0.01) growth, but not food intake. Large energy:protein diets (> 53 MJ/kg protein) and dietary T3 lowered (P < 0.01) plasma growth hormone. Large energy:protein diets (> 53 MJ/kg protein) increased (P < 0.01) lipogenesis, plasma growth hormone (GH) and decreased plasma insulin-like growth factor 1 (IGF-1). Also, T3 decreased plasma GH, IGF-1 in vitro lipogenesis. Ouabain inhibited a greater proportion of in vitro lipogenesis in those explants synthesizing fat at a high rate. Both dietary T3 and in vitro ouabain decrease lipogenesis, but, when combined, the effects are not cumulative.