Endotoxin challenge increases xanthine oxidase activity in cattle: effect of growth hormone and vitamin E treatment

In addition to its basic role in the metabolism of purine nucleotides, xanthine oxidoreductase (XOR) is involved in the generation of oxygen-derived free radicals and production and metabolic fate of nitric oxide (NO). Growth hormone (GH) and Vitamin E (E) have been shown previously to modify immune response to infection. Our objective was to determine in heifers the effect of endotoxin challenge (LPS; 3.0 μg/kg BW, i.v. bolus, Escherichia coli 055:B5) on xanthine oxidase (XO) activity in plasma and liver and the modification of this response by daily treatment with recombinant GH (0.1 mg/kg BW, i.m., for 12 days) or GH+E (E: mixed tocopherol, 1000 IU/heifer, i.m., for 5 days). In experiment 1, 16 heifers (348.7±6.1 kg) were assigned to control (C, daily placebo injections), GH, or GH+E treatments and were challenged with two consecutive LPS injections (LPS1 and LPS2, 48 h apart). After LPS1, plasma XO activity increased 290% (P<0.001) at 3 h, reached peak (430%) at 24 h and returned to basal level by 48 h after LPS2. XO responses (area under the time×activity curve, AUC) were greater after LPS1 than LPS2 (P<0.001). Total plasma XO responses to LPS (AUC, LPS1+LPS2) were augmented 55% (P<0.05) over C with GH treatment but diminished to C responses in GH+E. There was a linear relationship (r²=0.605, P<0.001) between total response in plasma XO activity and plasma nitrate+nitrite concentration. In experiment 2, 24 heifers (346±6 kg) were assigned to C or GH treatments and liver biopsy samples were obtained at 0, 3, 6, and 24 h after a single LPS challenge. Hepatic XO activities increased 63.3% (P<0.05) 6 h after single LPS challenge and remained elevated at 24 h (100.1%, P<0.01) but were not affected by GH treatment. Results indicate that LPS-induced increases in plasma XO activity could be amplified by previous GH treatment but attenuated by E administration. The data also suggest that E may be effective in controlling some mediators of immune response associated with increased production of NO via the effect on XO activity and its production of superoxide anion as well as uric acid.     

激素和生长因子调控奶牛乳腺发育的研究进展

生长激素及同期发情技术等目前较好地应用于奶牛场的生产,但是生长因子、转录因子、受体及细胞内信号等因素最终决定了乳房发育的大小和泌乳能力的强弱。这些因素还有待进一步研究以指导生产实践。     

Bovine growth hormone gene polymorphism affects stress response in Japanese Black cattle

We investigate the associations between growth hormone (GH) gene polymorphism and behavioral and physiological responses to stressors and learning ability in Japanese Black cattle. Flight distance test was conducted in the first experiment. Steers with haplotype C of GH gene polymorphism avoided human approaches at a significantly greater distance than ones without haplotype C (C: 1.9 ± 0.9, non‐C: 1.0 ± 0.2 m, P < 0.05). An open‐field test was conducted in the second experiment. Behavioral responses did not differ significantly between steers with and without haplotype C. Increases of heart rates to dropping of iron pipes was significantly higher in steers with haplotype C (C:161.7 ± 21.8, non‐C:130.7 ± 31.3%, P < 0.05). Despite basal serum concentrations not being different between steers with and without haplotype C, serum cortisol in blood sampling immediately after severe confinement in a race tended to be higher in steers with haplotype C (P = 0.1). The maze test was conducted as the third experiment. There was no difference in performance in the maze test between steers with and without haplotype C. It is concluded that genetic polymorphism of GH may affect stress responses through GH concentration in steers.     

Developmental programming: the role of growth hormone

Developmental programming of the fetus has consequences for physiologic responses in the offspring as an adult and, more recently, is implicated in the expression of altered phenotypes of future generations. Some phenotypes, such as fertility, bone strength, and adiposity are highly relevant to food animal production and in utero factors that impinge on those traits are vital to understand. A key systemic regulatory hormone is growth hormone (GH), which has a developmental role in virtually all tissues and organs. This review catalogs the impact of GH on tissue programming and how perturbations early in development influence GH function.     

Injection of porcine growth hormone releasing hormone gene plasmid in skeletal muscle increases piglets' growth and whole body protein turnover

The aim of the current study was to investigate the effects of a porcine growth hormone releasing hormone (pGHRH) gene plasmid injection in piglets on growth performance and whole body protein turnover. Sixty male Canadian Landrace × Chinese Taihu piglets were assigned to an intramuscular injection of 0 (control), 0.25, 0.5, 1 and 2 mg. All pigs were fed with the same diet (crude protein: 239.8 g/kg, digestible energy: 14.28 MJ/kg) at ad libitum intake. Protein turnover was determined on the 22nd day with a three-pool model by using a single-dosage, end-product analysis method with ¹⁵ N-glycine as a tracer. Injection of the pGHRH gene plasmid increased the piglets' growth rate, altered feed intake and decreased feed conversion ratio. It increased plasma growth hormone releasing hormone (GHRH), growth hormone (GH), insulin-like growth factor-I (IGF-I) and somatostatin but reduced serum urea and triglyceride. It reduced the urinary nitrogen excretion and led to higher nitrogen retention as well as the efficiencies of nitrogen retention and digestible N utilization. It increased the rates of protein synthesis, protein breakdown and net protein gain. Excretion of endogenous urinary nitrogen was reduced and nitrogen reutilization rate was improved. Conclusions: Injection of the pGHRH gene plasmid in skeletal muscle stimulated GHRH, GH and IGF-I excretion in piglets. Protein deposition was increased by an increase in protein synthesis and a smaller increase in protein breakdown, which was accompanied by reducing amino acid oxidation and increasing nitrogen reutilization.     

Genetic diversity of growth hormone receptor gene in cattle

Growth hormone receptor (GHR) belongs to a member of the cytokine receptor superfamily. Polymorphism of presence or absence of an approximately 1.2 kbp LINE-1 element is observed in bovine GHR gene. The present study was carried out for estimating the genetic diversity and the origin of the LINE-1 element in 10 European, Southeastern Asian and East Asian cattle breeds or populations. Genotyping of the LINE-1 revealed predominant LINE-1 presence in European breeds (0.917∼0.991), absence in the Bos taurus indicus populations (0.000∼0.017), and intermediate presence in Northeast Asian cattle (0.417∼0.522). From genetic features of LINE families, LINE-1 of GHR could be attributed to the same origin in both European and Asian cattle, and Asian LINE-1 may not be derived from recent introgression. This result suggested that LINE-1 in bovine GHR gene could have arisen in an ancestral population of Bos taurus taurus .     

Growth hormone stimulation of serum insulin concentration in cattle: Nutritional dependency and potential mechanisms

Previous studies on the effect of growth hormone (GH) on serum insulin concentration in cattle had generated seemingly conflicting results, and little was known about the mechanism by which GH affects serum insulin concentration in cattle, if it does. In this study, we determined whether the effect of GH on serum insulin concentration in cattle could be affected by the nutritional levels of the animal and whether GH increased serum insulin concentration in cattle by directly stimulating insulin release or insulin gene expression in the pancreatic islets. Administration of recombinant bovine GH increased serum insulin concentration in nonlactating, nonpregnant beef cows fed a daily concentrate meal in addition to ad libitum hay, but it had no effect in those cows fed hay only. Both GH treatments for 1 and 24 h increased insulin concentrations in cultures of pancreatic islets isolated from growing cattle. Growth hormone treatment for 24 h increased insulin mRNA expression in cultured bovine pancreatic islets. Growth hormone treatment for 16 h increased reporter gene expression directed by a ∼1,500-bp bovine insulin gene promoter in a rat insulin-producing β cell line. Taken together, these results suggest that exogenous GH can increase serum insulin concentration in cattle, but this effect depends on the nutritional levels of fed cattle, and that GH increases serum insulin concentration in cattle by stimulating both insulin release and insulin gene expression in the pancreatic islets.     

Secretory pattern and regulatory mechanism of growth hormone in cattle

The ultradian rhythm of growth hormone (GH) secretion has been known in several animal species for years and has recently been observed in cattle. Although the physiological significance of the rhythm is not yet fully understood, it appears essential for normal growth. In this review, previous studies concerning the GH secretory pattern in cattle, including its ultradian rhythm, are introduced and the regulatory mechanism is discussed on the basis of recent findings.     

Effect of growth hormone administration to mature miniature Brahman cattle treated with or without insulin on circulating concentrations of insulin-like growth factor-I and other metabolic hormones and metabolites

Previously, we determined that a primary cause of proportional stunted growth in a line of Brahman cattle was related to an apparent refractoriness in metabolic response to GH in young animals. The objective of this study was to determine the effect of administration of GH, insulin (INS), and GH plus INS to mature miniature Brahman cows (n = 6; 9.7 ± 2.06 y; 391 ± 48.6 kg) and bulls (n = 8; 9.4 ± 2.00 y; 441 ± 54.0 kg) on circulating concentrations of metabolic hormones and metabolites, primarily IGF-I and IGF-I binding proteins. We hypothesized that IGF-I secretion could be enhanced by concomitant administration of exogenous GH and INS, and neither alone would be effective. Animals were allotted to a modified crossover design that included four treatments: control (CON), GH, INS, and GH + INS. At the start of the study, one-half of the cattle were administered GH (Posilac; 14-d slow release) and the other one-half served as CON for 7 d. Beginning on day 8, and for 7 d, INS (Novolin L) was administered (0.125 IU/kg BW) twice daily (7:00 AM and 7:00 PM) to all animals; hence, the INS and GH + INS treatments. Cattle were rested for 14 d and then were switched to the reciprocal crossover treatments. Blood samples were collected at 12-hour intervals during the study. Compared with CON, GH treatment increased (P < 0.01) mean plasma concentrations of GH (11.1 vs 15.7 ± 0.94 ng/mL), INS (0.48 vs 1.00 ± 0.081 ng/mL), IGF-I (191.3 vs 319.3 ± 29.59 ng/mL), and glucose (73.9 vs 83.4 ± 2.12 mg/dL) but decreased (P < 0.05) plasma urea nitrogen (14.2 vs 11.5 ± 0.75 mg/dL). Compared with INS, GH + INS treatment increased (P < 0.05) mean plasma concentration of INS (0.71 vs 0.96 ± 0.081 ng/mL), IGF-I (228.7 vs 392.3 ± 29.74 ng/mL), and glucose (48.1 vs 66.7 ± 2.12 mg/dL), decreased (P < 0.01) plasma urea nitrogen (13.6 vs 10.4 ± 0.76 mg/dL), and did not affect GH (13.5 vs 12.7 ± 0.95 ng/mL). In the miniature Brahman model, both the GH and GH + INS treatments dramatically increased circulating concentrations of IGF-I in mature cattle, suggesting that this line of Brahman cattle is capable of responding to bioactive GH.     

Effects of growth hormone treatment on the expression of somatotropic axis genes in the skeletal muscle of lactating Holstein cows

This study focused on the expression of somatotropic axis genes in the skeletal muscle of dairy cattle. A slow-release recombinant bovine growth hormone (GH) (rbGH) formulation was administered to 5 cows, and saline solution (control) was administered to another 5 cows every 2 wk for a total of 10 wk, starting from the peak of lactation. Tissue and blood samples were collected on days 2 and 14 after each rbGH injection. As target genes insulin-like growth factor (IGF)-1, IGF-2, IGFBPs (1, 2, 3, 4, 5, 6), acute labile subunit (ALS), IGF-1 receptor (IGF-1R), GH receptor (GHR), and the known GHR 5′-UTR variants were selected as target genes, and their relative expression was measured using real-time polymerase chain reaction. In GH-treated cows, an increase in expression was observed for GHR 5′-UTR variant 1I on day 14 (P < 0.05), whereas a significant down-regulation of GHR (P < 0.05) was found after comparing values of treated cows between day 2 and day 14. However, only IGF binding proteins (BP)-5 was found to be appreciably up-regulated in GH-treated cows (P < 0.001), which may indicate the importance of this gene in the overall molecular response to GH administration. Our study indicated that GH treatment did not affect the expression of most somatotropic axis genes, despite the marked increase in GH and IGF-1 in blood (P < 0.001). Nor did it have a large impact on the proportion of GHR 5′-UTR variants in the skeletal muscle of lactating cows. Finally, although we observed a significant variation in the expression of some genes, it would appear that the differences between GH-treated cows and controls were not great enough to be considered as reliable indirect indicators of GH treatment in dairy cattle.     

Effects of growth hormone secretagogues on the release of adenohypophyseal hormones in young and old healthy dogs

The effects of three growth hormone secretagogues (GHSs), ghrelin, growth hormone-releasing peptide-6 (GHRP-6), and growth hormone-releasing hormone (GHRH), on the release of adenohypophyseal hormones, growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinising hormone (LH), prolactin (PRL) and on cortisol were investigated in young and old healthy Beagle dogs. Ghrelin proved to be the most potent GHS in young dogs, whereas in old dogs GHRH administration was associated with the highest plasma GH concentrations. The mean plasma GH response after administration of ghrelin was significantly lower in the old dogs compared with the young dogs. The mean plasma GH concentration after GHRH and GHRP-6 administration was lower in the old dogs compared with the young dogs, but this difference did not reach statistical significance. In both age groups, the GHSs were specific for GH release as they did not cause significant elevations in the plasma concentrations of ACTH, cortisol, TSH, LH, and PRL. It is concluded that in young dogs, ghrelin is a more powerful stimulator of GH release than either GHRH or GHRP-6. Ageing is associated with a decrease in GH-releasing capacity of ghrelin, whereas this decline is considerably lower for GHRH or GHRP-6.     

Bos indicus type of growth hormone receptor gene is retained in Japanese Black cattle

The growth hormone receptor (GHR) gene is responsible for growth and carcass traits, and polymorphisms associated with the variation of meat production are thought to occur in the liver‐specific promoter of the GHR gene in cattle. The aim of this study was to analyse the structure of the liver‐specific promoter of GHR in Japanese Black cattle, as the relationship between GHR polymorphism and meat production is poorly understood in this breed. Typically in European cattle, the LINE‐1 element, a family of retrotransposons, is inserted in the liver‐specific promoter. However, a short GHR promoter without the LINE‐1 sequence was found in the Japanese Black breed as in Bos indicus cattle. The frequency of the short allele was approximately 60%. In addition, 24 of 29 Holstein/Japanese Black crosses carried the short allele from their sire. The present result suggests that the short allele for GHR may be a candidate marker for improving meat production of Japanese Black cattle.     

Active immunization against ghrelin decreases weight gain and alters plasma concentrations of growth hormone in growing pigs

Ghrelin has been implicated in the control of food intake and in the long-term regulation of body weight. We theorize that preventing the ability of ghrelin to interact with its receptors, would eventually lead to decreased appetite and thereby decrease body weight gain. To test our hypothesis, pigs were actively immunized against ghrelin. Ghrelin((1-10)) was conjugated to BSA and emulsified in Freund's incomplete adjuvant and diethylaminoethyl-dextran. Primary immunization was given at 19 weeks of age (WOA), with booster immunizations given 20 and 40 days after primary immunization. Body weight (BW) and plasma samples were collected weekly beginning at 19 WOA, and feed intake was measured daily. Fourteen days after primary immunization, the percentage of bound (125)I-ghrelin in plasma from immunized pigs was increased compared with control animals (P<0.001). Voluntary feed intake was decreased more than 15% in animals that were actively immunized against ghrelin compared with controls. By the end of the experiment, immunized pigs weighed 10% less than control animals (P<0.1). Concentrations of GH were increased (P<0.05) in immunized pigs. Apoptosis was not observed in post-mortem samples obtained from the fundic region of the stomach. Our observations suggest that immunization against ghrelin induces mild anorexia. This procedure could potentially be used as a treatment to control caloric intake and obesity.     

Somatotropin response in vitro to corticosterone and triiodothyronine during chick embryonic development: Involvement of type I and type II glucocorticoid receptors

Corticosterone (CORT) can stimulate growth hormone (GH) secretion on embryonic day (e) 12 in the chicken. However, CORT failed to induce GH secretion on e20 in a single report, suggesting that regulation of GH production changes during embryonic development. Secretion in response to CORT during embryonic development is modulated by the thyroid hormones triiodothyronine (T₃) and thyroxine (T₄). Growth hormone responses on e12 involve both glucocorticoid (GR) and mineralocorticoid receptors (MR); however, involvement of MR has not been evaluated past e12. To further define changes in somatotroph responsiveness to CORT, pituitary cells obtained on e12–e20 were cultured with CORT alone and in combination with T₃ and GH-releasing hormone (GHRH). Growth hormone mRNA levels and protein secretion were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and radioimmunoassay (RIA), respectively. Corticosterone significantly increased GH mRNA and protein secretion on e12; however, mRNA concentration and protein secretion were unaffected on e20. Contributions of GR and MR in CORT responses were evaluated using GR and MR antagonists. Treatment with a GR-specific antagonist effectively blocked the CORT-induced increase in GH secretion on e12. The same treatment on e20 had no effect on GH secretion. These findings demonstrate that GR is directly involved in glucocorticoid stimulation of GH secretion at the time of somatotroph differentiation but is not regulatory at the end of embryonic development. We conclude that positive somatotroph responses to CORT are lost during chicken embryonic development and that GR is the primary regulator of CORT-induced GH secretion.     

Relationship of the bovine growth hormone gene to carcass traits in Japanese black cattle.

The bovine growth hormone gene (bGH) possesses three haplotypes, A, B and C, that differ by amino acid mutations at positions 127 and 172 in the fifth exon: (leucine 127, threonine 172), (valine 127, threonine 172) and (valine 127, methionine 172) respectively. The correlation between meat quality or carcass weight and these haplotypes was investigated in Japanese black cattle. Altogether, 940 bGH haplotypes were compared with respect to six carcass traits: carcass weight, longissimus muscle area, rib thickness, subcutaneous fat thickness, beef marbling score and beef colour. The frequency of the B haplotype was higher (0.421) than that of A (0.269) and C (0.311). High carcass weight and low beef marbling were associated with haplotype A (p < 0.05 and p < 0.01 respectively), whereas beef marbling was increased by haplotype C (p < 0.05). Estimated regression coefficient of the A haplotype substitution effect for carcass weight and beef marbling score were 5.55 (13.1% of the phenotypic SD) and -0.31 (17.0%) respectively. That of the C haplotype for beef marbling score was 0.20 (11.0%). The other traits showed no relationship to the haplotypes examined. The results of this investigation suggest that information pertaining to bGH polymorphisms in Japanese black cattle could be used to improve the selection of meat traits.     

Effect of atropine and pyridostigmine on growth hormone response to GH-releasing peptide-2 and GH-releasing hormone in swine

To investigate the effects of high and low somatostatinergic tone on GH-releasing peptide-2 (GHRP-2) and GH-releasing hormone (GHRH)-induced growth hormone (GH) secretion in swine, we examined GHRP-2- and GHRH-induced GH secretion after pretreatment with atropine or pyridostigmine. Pretreatment of swine with atropine (80 µg/kg bodyweight (BW), intravenous (i.v.)) 15 min before i.v. administration of saline, GHRP-2 (30 µg/kg BW), GHRH (1 µg/kg BW) or a combination of GHRP-2 and GHRH, reduced plasma GH area under the curve ( P  < 0.05), completely blocked GH response to GHRH, and attenuated GH response to GHRP-2 and GHRH combined ( P  < 0.05), without affecting GH response to GHRP-2 only. A synergistic effect of GHRP-2 and GHRH was not observed. In contrast, pretreatment of swine with pyridostigmine (100 µg/kg BW, i.v.), under the same pretreatment conditions as above, increased plasma GH concentration ( P  < 0.01), augmented GH response to GHRP-2 ( P  < 0.05), and GHRP-2 and GHRH combined ( P  < 0.05), but did not affect GH response to GHRH. These results suggest that the cholinergic muscarinic agents atropine and pyridostigmine modulate the GH response to GHRP-2 and GHRH, and that GHRP-2 acts antagonistically on the inhibitory effect of somatostatin in swine.     

Immunohistochemical expression of progesterone receptors, growth hormone and insulin growth factor-I in feline fibroadenomatous change

The immunohistochemical expression, tissue-specific and cell-specific distribution patterns of progesterone receptors (PR), growth hormone (GH) and insulin growth factor-I (IGF-I) have been studied in 22 cases of feline fibroadenomatous change (FFAC). PR and GH were detected in all cases and were distributed homogeneously throughout the lesion, while IGF-I was detected in 77% of the cases at the site of ductal budding. The simultaneous expression of PR, GH and IGF-I was detected in epithelial cells in 14 of 22 cases while PR and GH expression only was detected in epithelial cells in 11 cases. Cases that expressed GH and IGF-I without PR expression in the stroma were the most numerous. Double immunohistochemical staining showed the co-localisation of PR and GH in a subset of ductal epithelial cells located between basal/myoepithelial and luminal cells (probably undifferentiated stem cells). These results suggest that ligand-activated progesterone receptors may induce the local synthesis of GH which in turn may exert its proliferative action directly and also indirectly through the production of other growth factors, such as IGF-I, in an autocrine/paracrine manner.     

A two-sample method for assessing growth hormone response to growth hormone-releasing hormone challenge: use as a predictor of gain in beef bulls

In two experiments, Black Angus bulls were challenged at weaning with GHRH analog and evaluated for their GH response to determine whether GH response can predict subsequent growth characteristics. The GH response was determined by measuring GH in blood serum collected 0 and 10 min after GHRH injection (Exp. 1: 1.5 microg/100 kg BW human GHRH, n = 34; Exp. 2: 1.5 and 4.5 microg/100 kg BW bovine GHRH [treatments LGHRH and HGHRH, respectively] administered 3 h after a 4.5 microg/100 kg BW "clearance dose" of GHRH, n = 38]. In Exp. 1, GH response did not predict growth or carcass measurements. In Exp. 2, GH response to LGHRH was positively related to ADG (R2 = .18; P = .007) during a 112-d controlled feeding trial. In addition, there was a tendency for bulls with a greater GH response to HGHRH to exhibit greater ADG than animals with a low response. However, GH response to GHRH was not related to changes in hip height (HH) or carcass ultrasound measurements at d 112 of the growth performance trial. Response of GH to repeated GHRH challenges was consistent within animal over time (r = .47; P = .003). The use of a clearance dose 3 h prior to GHRH challenge improved the relationship between GH response and ADG. Results of this study suggest that GH response to GHRH challenge is a useful tool for identifying beef bulls with superior growth potential.