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In sheep, perinatal maturation of the endocrine arm of the insulin-like growth factor (IGF) system is characterized by two developmental events. First, concentrations of circulating IGF-I increase rapidly after birth and become responsive to changes in nutrition and growth hormone (GH). Second, the liver initiates synthesis of a serum protein called the acidlabile subunit (ALS). The acid-labile subunit promotes the endocrine actions of IGF-I and -II by recruiting them to long-lived complexes of 150 kDa. In this study, we examined the effect of nutrition on hepatic expression of the ALS gene around the time of birth and later in life. Expression of genes encoding other components of the circulating IGF system was also measured. At d 130 of fetal life, fetuses suffering from chronic undernutrition caused by placental insufficiency had lower expression of the ALS and IGF-I genes than well-nourished fetuses, but they did not have any changes in the expression of the IGF-binding protein (IGFBP)-2 or IGFBP-3 genes. In early postnatal life, hepatic gene expression was analyzed between d 12 and 38 in lambs fed a milk replacer at levels sustaining weight gains of 150 or 337 g/d. The lower plane of nutrition decreased the expression of the ALS, IGF-I, and GH receptor genes and increased the expression of the IGFBP-2 gene; expression of the IGFBP-3 gene was not affected by nutrition at this stage of life. Finally, hepatic gene expression was measured in 3-mo-old lambs offered ad libitum levels of a balanced diet or of a diet limiting for both energy and protein. Although the rate of growth of the lambs fed the limiting diet was reduced by 38%, the only effect detected in hepatic gene expression was a ninefold increase in the abundance of IGFBP-2 mRNA. Overall, these results indicate that undernutrition during late fetal and early postnatal life delays hepatic expression of the ALS gene and final maturation of the endocrine IGF system. Key Words: Fetus, Insulin-like Growth Factor, Liver, Postnatal Development, Somatotropin

Heat stress (HS) jeopardizes livestock health and productivity and both may in part be mediated by reduced intestinal integrity. Dietary zinc improves a variety of bowel diseases, which are characterized by increased intestinal permeability. Study objectives were to evaluate the effects of supplemental zinc amino acid complex (ZnAA) on intestinal integrity in heat-stressed growing pigs. Crossbred gilts (43±6 kg BW) were ad libitum fed one of three diets: (1) control (ZnC; 120 ppm Zn as ZnSO4; n=13), (2) control+100 ppm Zn as ZnAA (Zn220; containing a total of 220 ppm Zn; n=14), and (3) control+200 ppm Zn as ZnAA (Zn320; containing a total of 320 ppm Zn; n=16). After 25 days on their respective diets, all pigs were exposed to constant HS conditions (36°C, ∼50% humidity) for either 1 or 7 days. At the end of the environmental exposure, pigs were euthanized and blood and intestinal tissues were harvested immediately after sacrifice. As expected, HS increased rectal temperature (P⩽0.01; 40.23°C v. 38.93°C) and respiratory rate (P⩽0.01; 113 v. 36 bpm). Pigs receiving ZnAA tended to have increased rectal temperature (P=0.07; +0.27°C) compared with ZnC-fed pigs. HS markedly reduced feed intake (FI; P⩽0.01; 59%) and caused BW loss (2.10 kg), but neither variable was affected by dietary treatment. Fresh intestinal segments were assessed ex vivo for intestinal integrity. As HS progressed from days 1 to 7, both ileal and colonic transepithelial electrical resistance (TER) decreased (P⩽0.05; 34% and 22%, respectively). This was mirrored by an increase in ileal and colonic permeability to the macromolecule dextran (P⩽0.01; 13- and 56-fold, respectively), and increased colonic lipopolysaccharide permeability (P⩽0.05; threefold) with time. There was a quadratic response (P⩽0.05) to increasing ZnAA on ileal TER, as it was improved (P⩽0.05; 56%) in Zn220-fed pigs compared with ZnC. This study demonstrates that HS progressively compromises the intestinal barrier and supplementing ZnAA at the appropriate dose can improve aspects of small intestinal integrity during severe HS. [ABSTRACT FROM PUBLISHER]

Environmentally induced periods of heat stress decrease productivity with devastating economic consequences to global animal agriculture. Heat stress can be defined as a physiological condition when the core body temperature of a given species exceeds its range specified for normal activity, which results from a total heat load (internal production and environment) exceeding the capacity for heat dissipation and this prompts physiological and behavioral responses to reduce the strain. The ability of ruminants to regulate body temperature is species- and breed-dependent. Dairy breeds are typically more sensitive to heat stress than meat breeds, and higher-producing animals are more susceptible to heat stress because they generate more metabolic heat. During heat stress, ruminants, like other homeothermic animals, increase avenues of heat loss and reduce heat production in an attempt to maintain euthermia. The immediate responses to heat load are increased respiration rates, decreased feed intake and increased water intake. Acclimatization is a process by which animals adapt to environmental conditions and engage behavioral, hormonal and metabolic changes that are characteristics of either acclimatory homeostasis or homeorhetic mechanisms used by the animals to survive in a new 'physiological state'. For example, alterations in the hormonal profile are mainly characterized by a decline and increase in anabolic and catabolic hormones, respectively. The response to heat load and the heat-induced change in homeorhetic modifiers alters post-absorptive energy, lipid and protein metabolism, impairs liver function, causes oxidative stress, jeopardizes the immune response and decreases reproductive performance. These physiological modifications alter nutrient partitioning and may prevent heat-stressed lactating cows from recruiting glucose-sparing mechanisms (despite the reduced nutrient intake). This might explain, in large part, why decreased feed intake only accounts for a minor portion of the reduced milk yield from environmentally induced hyperthermic cows. How these metabolic changes are initiated and regulated is not known. It also remains unclear how these changes differ between short-term v. long-term heat acclimation to impact animal productivity and well-being. A better understanding of the adaptations enlisted by ruminants during heat stress is necessary to enhance the likelihood of developing strategies to simultaneously improve heat tolerance and increase productivity. [ABSTRACT FROM AUTHOR]

Heat stress has an enormous economic impact on the global dairy industry, but the mechanisms by which hyperthermia negatively affect systemic physiology and milk synthesis are not clear. Study objectives were to evaluate production parameters and metabolic variables in lactating dairy cows during short-term heat stress or pair-fed conditions coupled with bST administration. Twenty-two multiparous Holstein cows were subjected to 3 experimental periods: 1) thermoneutral conditions with ad libitum intake for 7 d (P1); 2) heat stress (HS) with ad libitum intake (n = 10) or pair-fed (PF) in thermoneutral conditions (n = 12) for 7 d (P2), and 3) 7 d of HS or PF in conditions as described in P2 with recombinant bovine somatotropin administered on d 1 (P3). All cows received an intravenous glucose tolerance test (GTT) on d 5 of each period. Heat stress conditions were cyclical and temperatures ranged from 29.4 to 38.9°C. Rectal temperatures and respiration rates increased during heat stress (38.6-40.4°C and 44-89 breaths/min, respectively). Heat stress reduced dry matter intake by 30% and by design PF cows had similar intake reductions (28%). During heat stress and pair-feeding, milk yield decreased by 27.6% (9.6 kg) and 13.9% (4.8 kg), respectively, indicating that reduced feed intake accounted for only 50% of the decreased milk production. Milk yield increased with recombinant bovine somatotropin in both HS (9.7%) and PF (16.1%) cows. Cows in both groups were in positive energy balance (3.95 Mcal/d) during P1 but entered negative energy balance during P2 and P3 (-5.65 Mcal/d). Heat stress and pair-feeding treatments decreased (9.3%) basal glucose concentrations. Heat stress conditions had no effect on basal NEFA levels during P2; however, PF cows (despite a similar calculated energy balance) had a 2-fold increase in basal NEFA concentrations. Both groups had increased plasma urea nitrogen levels during P2 and P3 compared with P1. Basal insulin levels increased (37%) during P2 and P3 in HS cows but did not differ between periods in PF cows. During P2 and compared with P1, PF cows had a decreased rate of glucose disposal, whereas HS cows had a similar disposal rate following the GTT. During P2 and compared with P1, PF cows had a reduced insulin response whereas HS cows had a similar insulin response to the GTT. In summary, reduced nutrient intake accounted for only 50% of heat stress-induced decreases in milk yield, and feed intake-independent shifts in postabsorptive glucose and lipid homeostasis may contribute to the additional reduction in milk yield. [ABSTRACT FROM AUTHOR]

Heat stress is detrimental to dairy production and affects numerous variables including feed intake and milk production. It is unclear, however, whether decreased milk yield is primarily due to the associated reduction in feed intake or the cumulative effects of heat stress on feed intake, metabolism, and physiology of dairy cattle. To distinguish between direct (not mediated by feed intake) and indirect (mediated by feed intake) effects of heat stress on physiological and metabolic indices, Holstein cows (n = 6) housed in thermal neutral conditions were pair-fed (PF) to match the nutrient intake of heat-stressed cows (HS; n = 6). All cows were subjected to 2 experimental periods: 1) thermal neutral and ad libitum intake for 9 d (P1) and 2) HS or PF for 9 d (P2). Heat-stress conditions were cyclical with daily temperatures ranging from 29.7 to 39.2°C. During P1 and P2 all cows received i.v. challenges of epinephrine (d 6 of each period), and growth hormone releasing factor (GRF; d 7 of each period), and had circulating somatotropin (ST) profiles characterized (every 15 min for 6 h on d 8 of each period). During P2, HS cows were hyperthermic for the entire day and peak differences in rectal temperatures and respiration rates occurred in the afternoon (38.7 to 40.2°C and 46 to 82 breaths/min, respectively). Heat stress decreased dry matter intake by greater than 35% and, by design, PF cows had similar reduced intakes. Heat stress and PF decreased milk yield, although the pattern and magnitude (40 and 21%, respectively) differed between treatments. The reduction in dry matter intake caused by HS accounted for only approximately 35% of the decrease in milk production. Both HS and PF cows entered into negative energy balance, but only PF cows had increased (approximately 120%) basal nonesterified fatty acid (NEFA) concentrations. Both PF and HS cows had decreased (7%) plasma glucose levels. The NEFA response to epinephrine did not differ between treatments but was increased (greater than 50%) in all cows during P2. During P2, HS (but not PF) cows had a modest reduction (16%) in plasma insulin-like growth factor-I. Neither treatment nor period had an effect on the ST response to GRF and there was little or no treatment effect on mean ST levels or pulsatility characteristics, but both HS and PF cows had reduced mean ST concentrations during P2. In summary, reduced nutrient intake accounted for just 35% of the HS-induced decrease in milk yield, and modest changes in the somatotropic axis may have contributed to a portion of the remainder. Differences in basal NEFA between PF and HS cows suggest a shift in postabsorptive metabolism and nutrient partitioning that may explain the additional reduction in milk yield in cows experiencing a thermal load. [ABSTRACT FROM AUTHOR]

In lactating dairy cows, the onset of negative net energy balance (EB) at parturition causes a reduction in plasma leptin and is also associated with increased concentration of growth hormone (GH) and decreased concentration of insulin. These observations raise the possibility that opposite changes in plasma insulin and GH are partly responsible for reduced plasma leptin. To test this hypothesis, we first examined the effects of undernutrition without the confounding influence of parturition by using late lactating dairy cows fed 120% of their nutrient requirements or restricted to 33% of maintenance requirements. Plasma leptin was reduced within 24 h of feed restriction, and was associated with increased plasma GH and decreased plasma insulin. Complete food deprivation for 48 h caused similar changes in the plasma concentration of leptin. To determine if an elevation in GH is responsible for the fall in plasma leptin, dairy cows were treated with excipient or bovine somatotropin in early lactation or in late lactation. Growth hormone treatment had no significant effect on plasma leptin irrespective of stage of lactation. Finally, the effects of insulin were studied by performing euglycemic hyperinsulinemic clamps in mid-lactating dairy cows. After 96 h of hyperinsulinemia, plasma leptin was increased significantly. These data indicate that insulin regulates plasma leptin in lactating dairy cows. They also suggest that, in undernourished lactating dairy cows, reduced plasma insulin could account for a portion of the decline in plasma leptin but that elevated plasma GH is unlikely to have a major effect. [ABSTRACT FROM AUTHOR]

Steady-state levels of mRNA are often used to infer treatment effects on the levels of the corresponding protein. In addition, an internal standard RNA is usually measured to document specificity of treatment and to correct for intersample variation. Our objective was to evaluate whether glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and cyclophilin could be used as internal standards when studying changes in hepatic gene expression in dairy cows. Hepatic expression of GAPDH and cyclophilin was measured in 6 cows in late pregnancy (28 d prepartum) and early lactation (10 d postpartum). Each gene displayed 2- to 3-fold higher expression in early lactation than in late pregnancy. Next, we determined whether negative energy balance alone or in combination with exogenous growth hormone could mimic the effects of early lactation. Latelactating cows were fed 120% of predicted energy requirements or 33% of maintenance requirements. During each feeding period, cows were administered excipient or bovine somatotropin in a single-reversal design with 4-d periods separated by a 2-d interval. Underfeeding increased hepatic expression of GAPDH and cyclophilin by 1- to 2-fold, whereas bovine somatotropin had no effect. Finally, the effects of insulin were studied by performing hyperinsulinemic-euglycemic clamps in late pregnancy (28 d prepartum) and early lactation (28 d postpartum). Hyperinsulinemia reduced GAPDH expression in both states, and cyclophilin expression in early lactation. In conclusion, GAPDH and cyclophilin are regulated in the liver of dairy cows and should not be used to standardize hepatic gene expression in studies involving the transition period, undernutrition, and sustained changes in plasma insulin. [ABSTRACT FROM AUTHOR]