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Calves are born vitamin A and beta-carotene deficient and the beta-carotene conversion to vitamin A is limited. Colostrum, contains relatively large amounts of vitamin A and beta-carotene and the retinol and beta-carotene status of calves can be normalized with colostrum consumption. We studied whether vitamin A supplementation of cows during late gestation (dry period) increases cow plasma retinol concentrations, the retinol content of first colostrum, and the plasma vitamin A status of calves during their first month of life. Both plasma and colostrum retinol concentrations were higher in vitamin A supplemented cows than in non-supplemented cows. In calves that were for 5 days fed colostrum (milk) from vitamin A-supplemented cows and then mature milk, plasma retinol concentrations were higher from 14 to 30 days after birth than in calves that were fed colostrum (milk) from cows that were not vitamin A supplemented. The study shows that vitamin A supplementation of cows during the dry period can improve the vitamin A status of their calves up to 1 month, if calves ingest their colostrum/milk for up to 5 days.

Colostrum feeding and glucocorticoid administration affect glucose metabolism and insulin release in calves. We have tested the hypothesis that dexamethasone as well as colostrum feeding influence insulin-dependent glucose metabolism in neonatal calves using the euglycemic-hyperinsulinemic clamp technique. Newborn calves were fed either colostrum or a milk-based formula (n=14 per group) and in each feeding group, half of the calves were treated with dexamethasone (30 microg/[kg body weight per day]). Preprandial blood samples were taken on days 1, 2, and 4. On day 5, insulin was infused for 3h and plasma glucose concentrations were kept at 5 mmol/L+/-10%. Clamps were combined with [(13)C]-bicarbonate and [6,6-(2)H]-glucose infusions for 5.5h (i.e., from -150 to 180 min, relative to insulin infusion) to determine glucose turnover, glucose appearance rate (Ra), endogenous glucose production (eGP), and gluconeogenesis before and at the end of the clamp. After the clamp liver biopsies were taken to measure mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC). Dexamethasone increased plasma glucose, insulin, and glucagon concentrations in the pre-clamp period thus necessitating a reduction in the rate of glucose infusion to maintain euglycemia during the clamp. Glucose turnover and Ra increased during the clamp and were lower at the end of the clamp in dexamethasone-treated calves. Dexamethasone treatment did not affect basal gluconeogenesis or eGP. At the end of the clamp, dexamethasone reduced eGP and PC mRNA levels, whereas mitochondrial PEPCK mRNA levels increased. In conclusion, insulin increased glucose turnover and dexamethasone impaired insulin-dependent glucose metabolism, and this was independent of different feeding.

The gastrointestinal tract of neonatal calves is relatively mature but still requires morphological and functional changes. The intake of colostrum with its nutrient and non-nutrient components exerts marked effects on gastrointestinal development and function. Colostrum intake provides immunoprotection (passive immunity by immunoglobulins) and is essential for survival of neonates of most species. Furthermore, there are important transient as well as long-lasting systemic effects on the nutritional status, on metabolism, and on various endocrine systems due to intake of nutrient and non-nutrient colostral components that contribute to survival in the stressful postnatal period. Colostrum is much more than just a supplier of immunoglobulins.

Nuclear receptors (NR), including retinoic acid and retinoid X receptors (RAR, RXR), pregnane X receptor (PXR), constitutive androstane receptor, and peroxisome proliferator-activated receptor (PPARalpha) modify the expression of other genes, such as cytochrome p450 enzymes (CYP), sulfotransferases (SULT), and UDP glucuronosyl transferases (UGT). Nuclear receptor expression is influenced by exposure to ligands (e.g., vitamin A). We tested the hypothesis that vitamin A feeding influences the expression of hepatic and intestinal NR and their target genes and that colostrum or formula feeding influence these traits differently. Calves (n = 7/ group) were fed colostrum (CO) or a milk-based formula with or without vitamin A (FA, FO, respectively) for 4 d and were euthanized on d 5, followed immediately by tissue collection. Thereafter, RNA was extracted and gene expression quantified by real-time reverse transcription-polymerase chain reaction. Expression relative to housekeeping genes of mRNA was profiled for NR, CYP, SULT, and UGT enzymes. Hepatic mRNA levels of RARbeta and CYP26 were higher in FA than FO cows; expression of CYP2E1, CYP2C8, CYP26, and UGT1A1 was higher in CO than FO cows; and expression of CYP2E1, UGT1A1, and p450 reductase was higher in CO than FA. In colon tissue, abundance of RXRalpha mRNA was lower in FO than CO, and CYP2B6 expression was lower in FO than in CO and FA. In jejunal tissue, there were no significant differences in gene expression among groups. In conclusion, effects of vitamin A feeding were limited, but colostrum feeding had several selective effects on expression of nuclear receptors and target genes.

Glucocorticoids increase plasma glucose concentrations in neonatal calves, but not hepatic gluconeogenic enzyme mRNA levels and activities. Catecholamines, too, enhance plasma glucose levels and regulate hepatic glucose metabolism. We have measured hepatic mRNA levels of beta-adrenergic receptors and beta-adrenergic receptor binding in neonatal calves on day 5 of life. Calves were fed either colostrums (C) or an isoenergetic milk-based formula (F), and in each feeding group, half of the calves were treated with dexamethasone (DEXA; 30 microg/(kg body weightday)). Abundance of mRNA was highest (P < 0.01) for beta2-adrenergic receptors and was higher (P < 0.01) for beta1- than for beta3-adrenergic receptors. DEXA treatment decreased (P < 0.05) beta1- and beta2-adrenergic receptor mRNA levels. Beta3-adrenergic receptor mRNA levels were higher (P < 0.05) in colostrum- than in formula-fed calves. Competitive binding revealed highest affinities for alprenolol, propranolol (both beta1- and beta2-antagonists), and ICI-188,551 (beta2-antagonist), which did not significantly differ from each other. Atenolol (beta1-antagonist) up to 10(-5) M did not displace (3H)-CGP-12177 from receptors. Competitive binding for adrenaline was best fitted by a two-receptor model. DEXA decreased (P < 0.05) (3H)-CGP-12177 binding capacities, whereas binding affinity of (3H)-CGP-12177 was not affected by DEXA or different feeding. Binding sites correlated positively with mRNA levels of beta2-adrenergic receptors (r = 0.56; P < 0.01). In conclusion, beta2-adrenergic receptors were the dominant subtype in the hepatic tissue. Feeding did not significantly affect beta2-adrenergic binding sites. However, DEXA decreased beta2-adrenergic binding sites and this was regulated at the transcriptional level.

Plasma leptin concentrations depend on energy intake and fat stores and are modified by hormones, such as glucocorticoids. We have measured plasma leptin concentrations in pre-term calves (born on day 277 of gestation) during the first week of life, in full-term calves (290 days of gestation), fed similar amounts of nutrients with colostrum or a milk-derived formula, combined with or without dexamethasone treatment (to simulate a high glucocorticoid status), during the first five days of life, and in calves fed with an automatic feeder or by bucket or suckling on dams up to day 28. Leptin concentrations increased (P<0.05) from birth to day 7 in pre-term calves. In full-term calves leptin concentrations were stable from day 1 to day 4 in colostrum-fed animals, but decreased (P<0.05) and were lower (P<0.05) if fed a formula with similar amounts of energy and macronutrients as colostrum. Concentrations increased (P<0.05) from day 1 to day 2 in calves suckling on dams and then remained elevated, but did not change and were lower in calves fed with the automatic feeder or by bucket than in suckling calves. Dexamethasone only slightly elevated leptin concentrations. There was no episodic secretion pattern, and there were no consistent associations of leptin with various metabolites and hormones. In conclusion, plasma leptin in young calves with respect to effects of nutrition (low energy intake) and hormones (glucocorticoids) and in association with metabolic changes behaved differently from what is known in mature cattle.

Intestinal diseases in neonatal calves may be due to morphological and functional immaturity. We have studied histomorphology, crypt cell proliferation rates (based on incorporation of 5-bromo-2'-deoxyuridine into DNA), presence of apoptotic cells (based on terminal deoxynucleotidyl transferase-mediated X-dUTP nick end labeling), and brush border enzyme activities in preterm calves (277 d of gestation), euthanized on d 1 (P0) or 8 (P8), and in full-term calves (290 d of gestation), euthanized on d 1 (F0) or 8 (F8). Vacuolated epithelial cells were present in ileum of P0 and F0 but not in P8 and F8. During the first 8 d, villus sizes, crypt depths, and proliferation rates of crypt cells in the small intestine of preterm calves did not significantly change. In contrast, in full-term calves during the first 8 d, villus sizes in jejunum decreased, crypt depths increased in small intestine and colon, and crypt cell proliferation increased in duodenum and jejunum. Submucosal thickness in jejunum was highest in P0, but in ileum it increased with gestational age and feeding. Gestational age x feeding interactions indicated increased activities of aminopeptidase N and reduced lactase activities only in F8 and reduced dipeptidylpeptidase IV activities only in P8. In conclusion, in preterm calves the small intestinal epithelium was immature and brush border enzyme activities differed in part from those in full-term calves.

The somatotropic axis regulates growth of the gastrointestinal tract (GIT). In addition, colostrum feeding and glucocorticoids affect maturation of the GIT around birth in mammals. We have measured mRNA levels of members of the somatotropic axis to test the hypothesis that colostrum intake and dexamethasone treatment affect respective gene expression in the GIT. Calves were fed either colostrum or an isoenergetic milk-based formula, and in each feeding group, half of the calves were treated with dexamethasone (DEXA; 30 microg/kg body weight per day). Individual parameters of the somatotropic axis differed (P < 0.05) among different GIT sections and formula feeding increased (P < 0.05) mRNA levels of individual parameters at various sites of the GIT. Effects of DEXA on the somatotropic axis in the GIT partly depended on different feeding. In colostrum-fed calves, DEXA decreased (P < 0.05) mRNA levels of IGF-I (esophagus, fundus, duodenum, and ileum), IGF-II (fundus), IGFBP-2 (fundus), IGFBP-3 (fundus), IGF1R (esophagus, ileum, and colon), IGF2R (fundus), GHR (fundus), and InsR (esophagus, fundus), but in formula-fed calves DEXA increased mRNA levels of IGF-I (esophagus, rumen, jejunum, and colon). Furthermore, DEXA increased (P < 0.05) mRNA levels of IGF-II (pylorus), IGFBP-3 (duodenum), IGF2R (pylorus), and GHR (ileum), but decreased mRNA levels of IGFBP-2 (ileum), and IGF1R (fundus). Whereas formula feeding had stimulating effects, effects of DEXA treatment on the gene expression of parameters of the somatotropic axis varied among GIT sites and partly depended on feeding.

The neonatal development of the gastrointestinal tract around parturition in precocious mammals is greatly affected by endocrine factors like glucocorticoids as well as by nutritional factors. We have studied the effects of glucocorticoids and colostrum supply on intestinal morphology, cell proliferation, digestive enzyme activities, and xylose absorption in neonatal calves to test the hypothesis that the intestinal development in neonatal calves is influenced by glucocorticoids, dependent on colostrum feeding. Calves designated GrFD(-) and GrFD(+) were fed a milk-based formula, whereas those designated GrCD(-) and GrCD(+) received colostrum. Dexamethasone (DEXA; 30 microg/kg/day) was injected at feeding times to calves of GrFD(+) and GrCD(+). On day 3, the D-xylose absorption was measured. The calves were euthanized on day 5 of life. Colostrum feeding increased villus sizes in jejunum and ileum, enhanced xylose absorption capacity, and increased peptidase activities in the ileum. DEXA treatment diminished sizes and cell proliferation rates of Peyer's patches in the ileum, yet increased proliferation of crypt cells in the ileum of formula-fed calves. DEXA reduced aminopeptidase N activities in the jejunum of formula-fed calves, but increased the peptidase activities mainly of colostrum-fed calves in the ileum. Thus, DEXA effects depended on intestinal segment and on different feeding, resulting in stimulation of crypt cell proliferation in the less mature ileum (of formula-fed calves) and in stimulation of peptidase activities in the more mature ileum (of colostrum-fed calves). We conclude that the effects of DEXA were related to the developmental stage of the neonatal intestine and promoted the intestinal development, depending on the developmental stage., (Copyright 2004 S. Karger AG, Basel)

Plasma glucose concentrations in neonates are influenced by colostrum feeding and by glucocorticoids. We have tested whether a high-glucocorticoid status after birth, as well as colostrum feeding, influences glucose metabolism in association with changes of hepatic expression and activities of gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) and pyruvate carboxylase (PC; EC 6.4.1.1) in neonatal calves. Calves (n = 14 per group) were fed either colostrum or a milk-based formula with nutrient and energy contents similar to colostrum. Half the calves in each feeding group were treated with dexamethasone (DEXA; 30 microg/[kg BW x d]). Pre- and postprandial blood samples were taken on d 1, 2, 4, and 5 and liver samples were collected on d 5 of life. Dexamethasone treatment increased (P < or = 0.05) plasma concentrations of glucose, insulin, and glucagon more in colostrum-fed than in formula-fed calves but increased (P < or = 0.05) urea concentrations and decreased (P < or = 0.05) concentrations of NEFA, ACTH, and cortisol independent of colostrum vs. formula feeding. Colostrum feeding increased (P < 0.05) plasma glucose, but decreased (P < 0.05) plasma urea concentrations. Glucagon-to-insulin ratios in DEXA-treated and colostrum-fed calves were decreased (P < 0.05). Dexamethasone treatment decreased hepatic mRNA levels and activities of PC (P < 0.001 and P < 0.10) and activities of PEPCK (P < 0.001) but increased (P < 0.001) the glycogen content. Colostrum feeding increased (P < 0.05) mitochondrial PEPCK mRNA levels and PEPCK activities in calves not treated with DEXA but decreased (P < 0.1) amounts of PC mRNA. In conclusion, increased plasma glucose concentrations after DEXA treatment were not associated with a stimulation of hepatic gluconeogenic enzyme activities; however, colostrum feeding probably raised plasma glucose concentrations because of increased hepatic gluconeogenic activities.

An increased susceptibility to disease in neonatal calves may be attributable to high glucocorticoid levels that influence immune reactions. We tested whether dexamethasone (DEXA) administration influences the proliferation, apoptosis, and number of B- and T-lymphocytes in Peyer's patches (PP) and thymus in calves fed colostrum (C) or a milk-derived formula. All calves were subcutaneously administered bovine colostrum-derived immunoglobulin G and fed chicken-egg derived immunoglobulins that protected against rotavirus and pathogenic Escherichia coli. The DEXA (30 microg/kg of BW daily) was injected for 4 d into groups fed colostrum on the first 3 d (CD+) and those fed the formula that contained nutrients in amounts as in colostrum but no immunoglubulin G (FD+). Groups CD- and FD were fed the same as the other two groups, but did not receive DEXA. Immunohistochemical methods were used to evaluate cell proliferation rates (by labeling of 5-bromo-2'-deoxyuridine), apoptosis rates (by terminal deoxynucleotidyl transferase-mediated X-dUTP nick end labeling). Numbers of T- and B-lymphocytes were determined with antibodies specific for CD3 and CD79 surface proteins. There were significant effects (P < 0.05) of DEXA treatment (decrease of cell proliferation rates in follicles of PP and thymus, increase of apoptotic rate in follicles of PP and thymus, decrease of B-lymphocyte numbers in follicles of PP, increase of B-lymphocyte numbers in domes of PP, increase of T-lymphocyte numbers in follicles of PP, and a decrease of intraepithelial T-lymphocyte numbers). There were significant effects (P < 0.05) of C feeding (decrease of cell proliferation rates in follicles of PP and of B-lymphocyte numbers in interfollicular areas, domes, and follicular-associated epithelium of PP, and an increase of cell proliferation rate in the thymus). A DEXA x feeding interaction (P < 0.001) was found for cell proliferation rate in the thymus. In conclusion, DEXA treatment decreased cell proliferation rates in follicles of PP and thymus and enhanced apoptotic rates in follicles of PP. Colostrum feeding decreased cell proliferation rates, likely of B-lymphocytes, in follicles of PP and numbers of B-lymphocytes in domes, follicular-associated epithelium, and interfollicular areas of PP and enhanced cell proliferation rates and selectively modified DEXA effects in the thymus.

Glucocorticoids and colostrum feeding influence postnatal maturation of the somatotropic axis. We have tested the hypothesis that dexamethasone (Dexa) affects the somatotropic axis in neonatal calves dependent on colostrum intake. Calves were fed either with colostrum or with a milk-based formula (n = 14/group), and, in each feeding group, one-half of the calves were treated with Dexa (30 micro g. kg body wt-1. day-1). Pre- and postprandial blood samples were taken on days 1, 2, 4, and 5, and liver samples were taken on day 5 of life. Dexa increased insulin-like growth factor (IGF)-I, but decreased growth hormone (GH) and IGF-binding protein (IGFBP)-1 and -2 plasma concentrations and increased GH receptor (GHR) mRNA levels in liver. Dexa increased IGF-I mRNA levels only in formula-fed calves and increased hepatic GHR binding capacity, but only in colostrum-fed calves. Colostrum feeding decreased IGFBP-1 and -2 plasma concentrations and hepatic IGFBP-2 and -3 mRNA levels. In conclusion, Dexa and colostrum feeding promoted maturation of the somatotropic axis. Dexa effects partly depended on whether colostrum was fed or not.

Experiments were designed to study compositional differences in colostrum and mature milk and during the course of milk removal. Fractionized milk samples during the course of machine milking were analyzed in single (right rear) quarters in the cisternal fraction, after 25, 50, 75, and 100% of spontaneously removed milk, in residual milk, and in composite samples from all quarters on d 2 (colostrum) and in wk 4 (mature milk) of lactation. Somatic cell counts; concentrations of dry matter, total protein, insulin-like growth factor-I, insulin, prolactin, tumor necrosis factor-alpha, Na, and Cl; gamma-glutamyltransferase activity; and electrical conductivity were higher, whereas lactose concentration was lower on d 2 than in wk 4. Concentrations of fat, potassium chloride, and osmolarity did not differ between lactational periods. During the course of milking, concentrations of dry matter, fat, lactose, and potassium, and osmolarity increased, whereas somatic cell counts, protein, insulin like-growth factor-I, insulin, prolactin, and sodium concentrations, electrical conductivity and gamma-glutamyltransferase activity decreased on d 2, and protein, sodium, and electrical conductivity decreased in wk 4. In conclusion, various milk constituents differed considerably between lactational periods (colostrum and mature milk). Milk isotonicity was only in part associated with lactose concentration. Electrical conductivity was associated with Na, K, and fat concentrations and was highest in the cisternal fraction. Changes in milk constituents during milking need to be considered if milk samples are taken for analytical purposes and to evaluate the health status of the udder.

Concentrations of nonnutritional factors, such as insulin-like growth factor-I (IGF-I), in bovine colostrum are high and can modulate neonatal gastrointestinal tract development and function. In neonatal calves, we have investigated effects on intestinal epithelial cell morphology, proliferation, and absorption of feeding milk-born human IGF-I (hIGF-I) or a bovine colostrum extract. Calves were fed a milk-based formula containing amounts of nutrients comparable to colostrum for the first 3 d and a milk replacer from d 4 on. Formula and milk replacer contained only traces of nonnutritional factors. In experiment 1, supraphysiological amounts of hIGF-I (3.8 mg/L formula; secreted by transgenic rabbits with their milk) were added to the formula. Xylose appearance in blood (after feeding xylose on d 5) and intestinal traits (after euthanasia on d 8) did not differ between groups. In experiment 2, an extract of first-milked bovine colostrum that provided physiological amounts of IGF-I (0.50, 0.15, and 0.09 mg of IGF-I/L formula on d 1, 2, and 3, respectively, and 0.09 mg of IGF-I/L milk replacer on d 4) was added to formula or milk replacer. Plasma xylose concentration in the control group was transiently higher than in calves fed the colostrum extract. On d 5 (after euthanasia), villus circumferences and heights in small intestine, and epithelial cell proliferation rate in intestine were higher in calves fed the colostrum extract than in controls. In conclusion, orally administered hIGF-I from transgenic rabbits had no effect on the intestinal tract. However, feeding a bovine colostrum extract enhanced intestinal villus size, although it appeared to transiently decrease the absorptive capacity.

Feed intake, growth performance, and metabolic and endocrine traits were studied in male calves fed unlimited (GrAL; n = 7) amounts of colostrum for 3 d after birth and mature milk up to d 28 and were compared with calves fed commonly recommended amounts of colostrum and milk (GrRS; n = 7). Calves were fed by automates, and software was available to continuously register the time points and amounts of ingested feed up to 11 d of age. Body weight was measured on d 1, 4, 7, 14, 21, and 28, and blood samples were taken on d 1, 2, 3, 7, 14, 21, and 28 to measure several metabolites and hormones. Feed intake of calves fed GrAL increased from d 1 to 4, then remained stable and was always higher than for calves fed GrRS. Total visits (visits with and without milk intake) were higher for GrRS than GrAL, but visits with milk intake were comparable between groups and meal sizes per visit with milk intake were greater in GrAL than in GrRS. Body weight gain was greater in GrAL than in GrRS in wk 1, but not later. There were significant group differences in plasma concentrations of albumin (GrRS > GrAL), nonesterified fatty acids (GrRS > GrAL), cholesterol (GrRS > GrAL; d 28), insulin (GrAL > GrRS), and cortisol (GrRS > GrAL), but not of immunoglobin G, urea, glucose, triglycerides, growth hormone, and glucagon. In conclusion, calves fed ad libitum were capable of ingesting very large amounts of colostrum and milk, even during wk 1 of life, accompanied by a greater body weight gain in GrAL in the first week, whereas in GrRS, the high number of visits without feed intake indicate that these calves reached no repletion. Compared with calves provided restricted amounts of feed, calves with free access to colostrum and milk were characterized by reduced plasma concentrations of nonesterified fatty acids and by a transiently enhanced insulin and reduced cortisol status.

The identification of hormones and regulatory factors in colostrum and milk has led to intensive investigations on their roles in the development and maintenance of the mammary and neonatal tissues. Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in transgenic mice influence mammary biology gland towards the end of lactation. In the bovine, IGFBP-3 is the major IGFBP in mammary secretions. In addition to binding IGFs, IGFBP-3 also binds to lactoferrin (Lf). Secreted IGFBP-3 re-enters mammary epithelial cells and with the presence of a nuclear localization sequence, IGFBP-3 and Lf enter the nucleus. Nuclear IGFBP-3 affects apoptotic signaling through the retinoic-x-receptors, while Lf affects apoptotic events through unknown mechanisms. Such interactions likely influence mammary development and involution. Furthermore, ingested colostral bioactive factors can exert regulatory functions in neonates. Intestinal receptors for IGFs and insulin are modified by age and/or diet. Feeding IGF-I had no effect, but colostrum extracts had small intestinal effects (stimulation of proliferation and villus size), suggesting that several factors, rather than one single bioactive factor were responsible. Systemic changes of metabolic and endocrine profiles in neonates depend on composition, amounts, time and duration of feeding colostrum. Early postnatal colostrum intake is not only important for the provision and absorption of immunoglobulins. Thus, in neonatal calves the lack of colostrum intake during the first 24h after birth results in a low immunoglobulin G, beta-carotene and Vitamin A status that persists for weeks and plasma patterns of fatty acids, essential amino acids and the glutamine/glutamate ratios are affected. In calves oral administration of IGF-I had no and feeding of colostrum whey extracts had only minor effects on metabolic and endocrine traits. Thus, mammary secretions influence regulatory functions of mammary and neonatal tissues.

Colostrum intake influences growth and development of the gastrointestinal tract (GIT) in several species and colostral insulin-like growth factors I and II (IGF-I and IGF-II), and insulin are involved in neonatal intestinal tissue growth. We have studied IGF type 1, IGF type 2, and insulin receptors in the intestine of 8-day-old calves fed different amounts of colostrum or only milk replacer. Calves were fed colostrum of the first six milkings on the first 3 days and then milk replacer (GrC(6)) or colostrum only once and then milk replacer (GrC(1)) or they were fed only milk replacer from the beginning, i.e., no colostrum (GrM). Competitive binding studies and ligand blots confirmed the presence of IGF type 1, IGF type 2, and insulin receptors in mucosal cell membranes of duodenum, jejunum, ileum, and colon. The IGF type 1 receptor number in ileum and total intestine in GrC(6) was greater (P<0.05) than in GrC(1) and in GrM, and IGF type 2 receptor number in total intestine was greater (P<0.05) in GrC(6) than in GrM. Insulin binding was best fitted by a model with two binding sites. High affinity insulin receptor numbers in duodenum, ileum, and total intestine were greater (P<0.05) in GrC(6) than in GrM. The data demonstrate that IGF type 1, IGF type 2, and insulin receptors in intestinal mucosa of neonatal calves are influenced by feeding.

We studied the effects of amounts of colostrum consumed on intestinal morphology and proliferation and digestive enzyme activities in neonatal calves. Group GrCmax calves were fed colostrum from the first milking undiluted on d 1-3 and diluted with 25, 50, 75 and 75 parts of a milk replacer on d 4-7. Group GrC1-3 calves were fed colostrum from milkings 1-6 up to d 3 and then a milk replacer up to d 7. Group GrF1-3 calves were fed a milk-based formula (containing only traces of growth factors and hormones) up to d 3 and then a milk replacer up to d 7. Calves were killed on d 8. Differences in feeding affected villus sizes and villus height/crypt depth ratios in the duodenum (GrCmax > GrC1-3), villus areas and villus height/crypt depth ratios in the jejunum (GrC1-3 > GrF1-3) and crypt depths in the colon (GrF1-3 > GrC1-3). Furthermore, different feeding protocols affected the proliferation rates of epithelial cells in the duodenum (GrC1-3 > GrCmax; GrC1-3 > GrF1-3) and the jejunum (GrF1-3 > GrC1-3; based on Ki-67 labeling). Lipase activities in the pancreas were influenced by colostrum feeding (GrC(max) > GrC(1-3)). Colostrum intake differentially affected intestinal epithelial surface and proliferation and enzyme activities. Feeding high amounts of first colostrum seemed to enhance the survival of mature mucosal epithelial cells in selected parts of the small intestine, whereas the lack of colostrum seemed to decrease epithelial growth.

Enzyme activities of gamma-glutamyltransferase (gamma-GT), alkaline phosphatase (AP) and aspartate-aminotransferase (AST) were measured from birth to the age of 28 days in calves which were fed colostrum at 0-2, 6-7, 12-13, or 24-25 h after birth. Enzyme activities were also measured in colostrum (first to fifth milking) and in mature milk. Activities were highest in the first colostrum milking and decreased to the lowest activities in mature milk. Plasma gamma-GT activity transiently increased after first colostrum intake and was greater in calves fed first colostrum within less than 6-7 h than in those fed first colostrum later than 12 h after birth. Activity of gamma-GT reflected the absorption of colostral gamma-GT, which decreased with time after birth. The AP activity transiently increased after colostrum intake and was higher in calves fed colostrum within the first 12 h of life than in those fed later after birth. The transient rise of plasma AP activity also indicated absorption of colostral AP, although endogenous sources of AP could not be excluded. The activity of AST also transiently increased after colostrum intake but there was no association with time of first colostrum feeding, indicating that the rise of plasma AST activity was the consequence of enhanced endogenous production and was independent of colostrum intake. In conclusion, there are different causes leading to postnatal changes in enzyme activities.

To test the hypothesis that delaying first colostrum feeding of calves after birth exerts long-lasting effects on haematological, metabolic and endocrine traits and on growth performance, neonatal calves were fed first colostrum at 0-2 and 24-25 h after birth. Delayed feeding of first colostrum for 24-25 h after birth caused reduced plasma levels of total protein and globulin for up to 30 days and of insulin-like growth factor-I for up to 7 days, whereas concentrations of nonesterified fatty acids were elevated during the first day of life. There were no significant effects of delaying feeding for 24-25 h on leucocyte and erythrocyte number, packed cell volume and on haemoglobin levels and on plasma concentrations of albumin, urea, glucose, triglycerides, phospholipids, cholesterol, insulin, growth hormone, 3.5.3'-triiodothyronine and thyroxine and on growth performance. Thus, calves fed first colostrum with a delay of 24-25 h after birth were able to compensate rapidly for nutritional deficiencies on day 1 of life, i.e. there was no evidence for permanent imprinting of haematological, metabolic and of endocrine traits by starvation on the first day of life.

Effects on beta-carotene, retinol and alpha-tocopherol status of feeding 1st colostrum at 0-2, 6-7, 12-13 and 24-25 h after birth were studied in calves. beta-carotene, retinol and alpha-tocopherol concentrations decreased in colostrum during the first 2.5 d of lactation. Plasma beta-carotene, retinol and alpha-tocopherol concentrations in newborn calves were very low. Plasma beta-carotene concentrations increased up to d 3 after the 1st meal and during the 1st month were higher in calves fed 1st colostrum at < 6-7 h than at > 12-13 h after birth. Plasma retinol concentrations increased up to d 5 after the 1st meal and were higher during the 1st month in calves fed 1st colostrum at < 12-13 h than at > 24-25 h after birth, whereas hepatic concentrations increased up to d 5 independent of time of 1st colostrum feeding. Plasma alpha-tocopherol concentrations increased after the 1st meal except in calves fed 1st colostrum at 24-25 h after birth and were higher during the 1st month in calves fed the 1st colostrum at 6-7 h than at 24-25 h after birth. In conclusion, delaying 1st colostrum intake by more than 12-13 h after birth impaired the plasma beta-carotene, retinol and alpha-tocopherol status during the 1st month of life, but did not negatively influence hepatic retinol concentrations.

Colostrum provides high amounts of nutrients and non-nutrient substances to neonates. To study differences between effects of nutritional and non-nutritional components on growth, health status and metabolic and endocrine traits, a formula was created based on bovine milk components which contained similar amounts of nutrients as bovine colostrum during the first 3 days of lactation, but only trace amounts of growth factors (such as insulin-like growth factor I) or hormones (such as insulin) in whey. Calves were fed either pooled colostrum of milkings 1 to 6, obtained during the first 3 days of lactation (GrC, n = 7) or a formula in the same amounts as colostrum (GrF, n = 7) for the first 3 days, followed by a milk replacer up to day 7. Pre- and postprandial blood samples were taken on days 1, 2, 3 and 7 for the determination of metabolic and endocrine traits and on day 5 we measured intestinal absorptive capacity by testing xylose absorption. Plasma concentrations of total protein and immunoglobulin G and gamma-glutamyltransferase activity were lower (p < 0.05), whereas albumin and urea concentrations were higher (p < 0.05) in GrF than GrC during the first week of life. Plasma glucose concentrations were variably affected. Plasma triglyceride, phospholipid and cholesterol concentrations were higher (p < 0.05) in GrC than GrF on days 3 and 7. Insulin and growth hormone concentrations were higher (p < 0.05) in GrC than GrF on days 2 and 3 and on days 1 and 2, respectively, and glucagon concentrations were higher (p < 0.05) in GrC than GrF on day 1 and higher (p < 0.05) in GrF than GrC on day 3. Cortisol concentrations were higher (p < 0.05) on days 2 and 3 in GrF than GrC. Plasma xylose concentrations rose more markedly (p < 0.05) in GrC than GrF. In conclusion, feeding only trace amounts of bioactive substances appears to impair intestinal absorptive capacity and protein and fat metabolism and exert effects on endocrine systems in neonatal calves., (Copyright 2000 S. Karger AG, Basel)

The intake of colostrum in newborn calves not only influences the immune status, but also the development of the gastrointestinal tract and other organs, metabolism and endocrine systems. Besides nutrients bioactive substances of colostrum have additionally to be considered. Metabolic and endocrine effects are transient, indications for metabolic and endocrine imprinting by differences in feeding in the first week of life have so far not been found. Nevertheless, changes observed in association with feeding especially of colostrum are considered important for the critical first week of life.

Colostrum intake is important for health and postnatal development of neonatal calves. We studied the effects of enhanced first colostrum feeding on growth, health status, and metabolic and endocrine traits in calves during their 1st wk of life. Calves of group CL (GrCL; n = 7) were fed colostrum of milkings 1 to 6 twice daily during the first 3 d of life, followed by milk replacer (MR) up to d 7. Calves of group CH (GrCH; n = 7) were fed colostrum of the first milking during the first 3 d and then colostrum (of the first milking) twice daily, which on d 4, 5, 6, and 7 was diluted with 25, 50, 75, and 75 parts of MR, respectively. Pre- and postprandial blood samples were taken on d 1, 2, 3, and 7 for the determination of various metabolic and endocrine traits, and on d 5 intestinal absorption capacity was measured using the xylose absorption test. Rectal temperatures and fecal scores were higher (P < .05) in GrCH than in GrCL. Plasma concentrations of total protein and albumin were higher (P < .05) on d 7, IgG on d 2 and 3, and urea on d 2, 3, and 7 in GrCH than in GrCL. Plasma concentrations of triglycerides were higher (P < .05) on d 2 and of phospholipids and cholesterol were higher (P < .01) on d 7 in GrCH than in GrCL. Plasma insulin and glucagon concentrations were higher (P < .05) in GrCH than in GrCL, whereas prolactin and growth hormone concentrations were higher (P < .05) in GrCL than in GrCH. Enhanced colostrum intake had no effects on xylose absorption on d 5. Higher plasma protein, urea, and lipid concentrations in GrCH partly mirrored higher protein and fat intake but additionally pointed to higher protein synthesis and lipid turnover.

Calves are born with a mostly inadequate essential amino acid (EAA) status. Studies were designed to test the hypothesis that delaying the intake of the first colostrum for 24 h, besides its early effects, also has late effects on plasma free amino acid levels and on the protein status. There were marked and rapid elevations (within 2 h) of plasma levels of various amino acids, and especially of EAA, after the intake of the first colostrum, whereas changes after the intake of mature milk on day 28 of life were mostly absent or concentrations even decreased. The EAA and non-essential amino acid (NEAA) status was rapidly normalized after intake of the first colostrum, but normal plasma levels of some amino acids were also reached during the first 24 h of life even when the first meal was withheld. Delaying colostrum intake had only transient effects on EAA and NEAA (except hydroxyproline), in contrast to its effects on plasma immunoglobulin G and total protein levels.

Colostrum (CO) contains high amounts, whereas whole milk and milk replacer (MR) contain small amounts, of bioactive and growth-promoting substances, such as IGF-I. An experiment was designed to study the effects of feeding CO or MR on the first 3 d to neonatal calves, followed by whole milk up to d 7, at low and high density. Intestinal absorptive capacity, plasma metabolite and hormone concentrations, and growth performance were measured during the 1st wk of life. Body weight increased (P < .05) similarly in calves fed low or high amounts of CO but did not rise in MR-fed calves. Loose feces were more frequent (P < .05) and absorption of xylose on d 5 was lower (P < .01) in MR- than in CO-fed calves, but there were no effects of feeding density within CO-fed or within MR-fed groups. However, high feeding density within CO-fed groups enhanced (P < .05) total protein, globulin, triglyceride, cholesterol, and insulin concentrations, whereas in the initially high and low MR-fed groups only plasma glucose and insulin after the first meal and plasma NEFA on d 2 were modified (P < .05) by different feeding density. Thus, feeding different amounts of CO partly influenced protein and fat metabolism in calves during the 1st wk of life, but it did not measurably affect intestinal function. However, feeding different amounts of MR, in the absence of CO, barely affected metabolic and endocrine traits and absorptive capacity. Thus, high density CO feeding, and therefore a high supply of nutrients, together with greater amounts of bioactive and growth-promoting substances influenced neonatal metabolism and growth more than a high density of MR feeding containing only small amounts of bioactive and growth-promoting substances. Factors in addition to nutrient density seem to be important for the development of neonatal calves.

In the neonatal calf, insulin-like growth factor I (IGF-I) concentrations are markedly influenced by the amount of colostrum intake after birth, although colostral IGF-I is barely absorbed. In this study we have investigated effects of delayed colostrum intake in neonatal calves on metabolic traits and on IGF-I, IGF binding proteins (IGFBP), growth hormone (GH), and insulin concentrations in plasma. Calves received colostrum of first milking starting at 2 (GrA), 6 (GrB), 12 (GrC), and 24 h (GrD) after birth. Before third colostrum intake plasma total protein concentrations were higher in GrA than in GrD and plasma glucose concentrations were higher in GrC than GrD. Plasma IGF-I concentrations at first and third colostrum intake were higher in GrA than in GrD. Plasma IGFBP-2 concentrations before first colostrum intake were higher in GrD than in GrA and GrC, and were higher before third colostrum intake in GrD than in GrA. Plasma IGFBP-3 concentrations before first colostrum intake were lower in GrD than in GrA, and before third colostrum intake were lower in GrD than in GrA and GrB. Postprandial plasma insulin concentrations after first colostrum intake were higher in GrA than in GrC and GrD. In conclusion, the plasma IGF-I and insulin status are markedly, albeit transiently, decreased in calves fed colostrum with a delay of 12 to 24 h, and the decreased concentrations of plasma IGF-I were associated with decreased IGFBP-3/IGFBP-2 ratios.

In neonatal calves besides adaptations in organ function there are marked metabolic and endocrine changes. The growth hormone (GH)-insulin-like growth factor (IGF) axis is basically functioning, but needs maturation. Various metabolic and endocrine traits do not exhibit marked ontogenetic changes after the first week of life, but others remain different from the adult stage. Thus, plasma oxytocin or an oxytocin-like substance and nitrate concentrations are elevated for months. The ability to digest colostrum (C) and milk involves great alterations in structure and function of the gastrointestinal (GI) tract. C intake is important for passive immunity, provision of nutrients, minerals and vitamins, and contains biologically active substances. IGF-I, present in C in high amounts, appears to enhance GI tract development and function. For sufficient absorption not only of immunoglobulins, but also of fatty acids and fat-soluble vitamins, C should be ingested immediately after birth. The amino acid pattern and the glutamine/glutamate ratio depends greatly on whether C is fed or not. Effects on insulin, IGF-I, and IGF binding proteins depend on time-point and amounts of C fed. After the colostral period calves are almost exclusively fed milk and milk substitutes or weaned. Low iron intake, required for the production of pale meat, besides anemia causes metabolic and endocrine adaptations, such as enhanced insulin-dependent glucose utilization and appears to reduce IGF-I responses to GH. Metabolic and endocrine changes, such as insulin resistance and disturbed glucose metabolism, can be observed in part in association with high feeding intensity in veal calves.

The effects of feeding different amounts of colostrum or only milk replacer and the effects of Long-R3-IGF-I (administered s.c. or orally; 50 microg/[kg BW x d] for 7 d), and of s.c. injected recombinant bovine GH (rbGH; 1 mg/[kg BW x d] for 7 d) on small intestinal mucosal morphology in newborn calves were studied by histomorphometry. Neonatal calves fed colostrum six times exhibited greater (P < .01) villus circumferences, areas, and heights in total small intestine and especially in the duodenum than calves fed only milk replacer. Furthermore, villus circumferences and areas in total small intestine were greater (P < .05) in calves fed colostrum once than in calves fed no colostrum. Villus size in total small intestine was smaller (P < .05) in rbGH-treated than in control calves; jejunum villus circumferences and heights were especially reduced (P < .05). Crypt depths in ileum were greater (P < .05) in rbGH-treated calves. In conclusion, prolonged colostrum supply significantly enhanced small intestinal villus size in neonatal calves. In contrast, Long-R3-IGF-I had no significant influence on small intestinal morphology, and rbGH in supraphysiological amounts even reduced small intestinal mucosal variables after 1 wk of treatment. The study demonstrated enhanced postnatal development of the gastrointestinal tract by prolonged colostrum feeding, but not by Long-R3-IGF-I or GH.

Bovine colostrum contains various essential nutrients, antibodies, hormones and growth factors that are important for nutrient supply, host defense, growth and for general neonatal adaptation. We have studied effects of colostrum fed for different durations on selected metabolic and endocrine traits in the first week of life in calves. Calves were fed colostrum twice daily for 3 d (group C6) or colostrum only as their first meal (group C1), followed by milk replacer up to d 7, or they were only fed milk replacer but no colostrum (group M). Plasma concentrations of immunoglobuline G and activities of enzymes (gamma-glutamyltransferase, aspartate-aminotransferase, lactate-dehydrogenase, glutamate-dehydrogenase) increased in groups C6 and C1 after first feeding, but not in group M. Postprandial plasma glucose concentrations on d 2 increased significantly more in groups C6 and C1 than in group M. Plasma triglycerides on d 2 and plasma phospholipid and cholesterol concentrations on d 7 were significantly higher in group C6 than in groups C1 and M. Plasma insulin concentrations on d 2 tended (P = 0.07) to increase more postprandially in group C6 than in group M and postprandial plasma glucagon concentrations on d 1 increased more in groups C6 and C1 than in group M and remained elevated on d 2 only in group C6. Plasma cortisol concentrations decreased postprandially in all three groups and were highest on d 2 and d 7 in group M. Plasma triiodthyronine and thyroxine concentrations decreased in the first week of life in all calves, whereas plasma prolactin concentrations were greatest on d 7 in group C6. In conclusion, various metabolic and endocrine traits were influenced by whether colostrum was fed and the duration of colostrum feeding.

Plasma immunoglobulin G (IgG) concentrations and gamma-glutamyltransferase (GGT) activities were measured in neonatal calves fed colostrum on days 1 and 2 of life, then milk up to day 7 (group C), while groups G and W were fed glucose or water, respectively, on day 1, colostrum on days 2 and 3 and milk up to day 7 of life. Glucose administration in group G on day 1 caused significantly more marked hyperglycaemias than in group C, while glucose concentrations in group W remained low. However, glucose concentrations on day 2 were significantly higher in group C than in groups G and W. Concentrations of IgG in group C significantly increased on day 1 and decreased after day 2, while GGT activity significantly increased after the first colostrum feeding only and decreased on day 2. Concentrations of IgG and GGT activity in groups G and W remained low on day 1 and increased on day 2. However, IgG remained significantly lower up to day 7 than in group C, while GGT reached the values of group C on day 2. Concentrations of IgG and activities of GGT on day 2 tended to increase less in group W than in group G. In conclusion, both plasma IgG concentration and GGT activity increased after colostrum intake, but only IgG remained elevated and thus informed on colostrum intake up to day 7. Intake of glucose relative to water did not significantly reduce the rise of IgG and GGT.

Colostrum contains numerous components that influence gastrointestinal development in neonates. To test the influence of differences in duration of colostrum feeding in newborn calves on gastrointestinal absorptive capacity, .5 g xylose/kg BW was administered on d 5 of life. Calves of group GrC6 were fed colostrum from the first six milkings on the first 3 d and then milk replacer. Calves of group GrC1 were fed first colostrum only and then milk replacer in the same amounts as calves of group GrC6. Calves of group GrM were fed only milk replacer: they received no colostrum. The rise of plasma xylose after xylose intake was greater (P < .05) in GrC6 and GrC1 than in GrM but not significantly greater in GrC6 than in GrC1. Basal and mean plasma glucose concentrations on d 5 of life were higher in GrC6 than in GrM, but there was no difference in the magnitude of its postprandial rise. The data indicate greater xylose absorptive capacity in calves after prolonged colostrum intake compared with calves fed only milk replacer.

To study whether a delayed start of colostrum feeding in calves affects plasma lipids, fatty acids and fat-soluble vitamins, one group was fed colostrum (milkings 1-4) on d 1 and 2, then mature milk up to d 7, whereas two other groups were fed glucose or water on d 1, colostrum (milkings 1-4) on d 2 and 3 and then mature milk up to d 7. In calves fed colostrum on d 1, starting 5-7 h after birth, plasma concentrations of triglycerides, phospholipids, total cholesterol and of essential and nonessential fatty acids in triglyceride, phospholipid and cholesterol ester fractions as well as of carotene, retinol and alpha-tocopherol up to d 7 were significantly higher than in calves in which colostrum feeding started after >24 h of life. On the other hand, plasma concentrations of vitamin B-6, vitamin B-12 and folic acid were not influenced. Results indicated reduced efficiency of absorption of colostral fatty acids and of fat-soluble vitamins, but not of (selected) water-soluble vitamins, if colostrum is not fed on d 1 of life. In conclusion, colostrum intake within the first 24 h of life is required for an adequate plasma lipid, essential fatty acid, carotene, retinol and alpha-tocopherol status in the first week of life of calves.

Effects on metabolic and endocrine traits of feeding colostrum on d 1 and 2, then mature milk up to d 7, or glucose or water on d 1, colostrum on d 2 and 3 and then mature milk up to d 7 were studied in calves. Calves fed colostrum within the first 24 h after birth had significantly higher rectal temperatures, heart rates and respiratory frequencies than calves provided only water or glucose. Significantly elevated plasma nonesterified fatty acid and bilirubin concentrations on d 1 and 2 of life in calves fed only water on d 1 compared with calves of the other groups mirrored reduced energy intake. Fecal consistency was significantly higher during wk 1 of life, and gastrin and glucose-dependent insulinotropic polypeptide increased only on d 1 and/or 2 of life in calves already fed colostrum on d 1, expressing improved functioning of the gastrointestinal tract. Significantly higher plasma globulin levels up to d 7 in calves fed colostrum on d 1 than in those starting colostrum intake only on d 2 demonstrated significantly enhanced efficiency of gamma-globulin absorption. Furthermore, significantly higher circulating glucose, albumin, insulin, insulin-like growth factor-I concentrations and significantly lower urea levels in calves fed colostrum on d 1 compared with those fed colostrum starting on d 2 of life indicated stimulation of anabolic processes. In conclusion, colostrum intake by calves within the first 24 h of life is needed not only for an adequate immune status, but also to produce the additional important and favorable effects on metabolic and endocrine traits and on vitality.