| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ANIMAL GROWTH, PHYSIOLOGY, AND REPRODUCTION |
Department of Animal Science, University of Connecticut, Storrs 06269
 |
Abstract |
|---|
 Top Abstract INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Key Words: age • beef cattle • growth rate • insulin-like growth factor • insulin-like growth factor binding protein • somatotropin
|
INTRODUCTION |
|---|
|
TopAbstractINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
), and may be a useful tool to increase efficiency of production in beef cattle. These bST-induced increases in growth rate are associated with changes in serum concentrations of components of the somatotropic axis (i.e., ST, IGF-I, and IGFBP-2 and -3; Rausch et al., 2002; Radcliffe et al., 2004). Although the somatotropic axis in beef cattle is responsive to exogenous bST as early as 1 d of age (Govoni et al., 2004), the magnitude of the growth response to bST is variable (Dalke et al., 1992; Houseknecht et al., 1992) and may depend, in part, on the age of the animal at the start of treatment. For example, there was no significant growth response to exogenous bST until cattle were at least 200 d of age, and the magnitude of the growth response was greater in older and heavier cattle (Rausch et al., 2002). Similarly, the magnitude of change in components of the somatotropic axis varies with age. Govoni et al. (2004) reported that the increase in IGFBP-3 and the decrease in IGFBP-2 concentrations in response to exogenous bST administration were more pronounced after 250 d of age in beef cattle. Taken together, these reports indicate that initiating bST treatment after 200 d of age will increase the magnitude of the physiological response to exogenous bST, including increased in growth rate. However, the optimal age to begin bST treatment to maximize bST-induced effects on growth rate, the efficiency of gain, and body composition is unknown. Therefore, the objectives of the current study were to determine growth rate, the efficiency of gain (G:F), and changes in measures of the somatotropic axis (ST, IGF-I, IGFBP-2, and IGFBP-3) in beef cattle to exogenous bST treatment beginning at 200, 250, or 300 d of age and continued until all the animals reached 400 d of age.
|
MATERIALS AND METHODS |
|---|
|
TopAbstractINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Hereford [n = 22; 11 females, 11 males (castrated at 152 ± 10 d of age)] and Angus [n = 18; 9 females, 9 males (castrated at 152 ± 10 d of age)] were housed unrestrained in covered pens (15 x 15 m) with an outside exercise area (15 x 35 m). Following weaning (at 180 ± 13 d), calves were blocked by BW and housed in 8 pens (5 animals/pen) balanced for breed and sex. Pens were randomly assigned to treatment groups (2 pens/treatment). Animals were fed outside in covered bunks. All groups received the same base total mixed diet, consisting of a mix of corn silage and a 52% protein supplement (95.5% forage to 4.5% supplement; 2.50 Mcal of ME and 100 g of protein/kg of DM). Previously, we have used a similar diet and reported bST-induced changes in growth rate (Tripp et al., 1998). This diet was formulated for animals to gain approximately 1.2 kg/d (NRC, 1984). Fresh feed was weighed and offered daily at 0800, and orts were recorded the following morning. Silage DM was analyzed every 2 wk using a Koster hay and silage moisture tester (Koster, Strongsville, OH). Water was provided for ad libitum consumption.
Exogenous bST Treatment and Sample Collection
Lyophilized bST (generously donated by Monsanto, St. Louis, MO) was reconstituted to make a bST solution (pH 9.5) of 10 mg/mL using 1 N NaOH, 50 mM EDTA, and distilled water. Exogenous bST injections (0.75 to 2.0 mL) were given at the tail head (s.c.) at a dose rate of 33 µg of bST/kg of BW daily for a period of up to 200 d, depending on treatment group. The amount of bST given to each animal was adjusted weekly according to its mean BW for that week. There were 3 bST treatment groups with animals beginning bST administration at 200 d of age (TRT200), 250 d of age (TRT250), and 300 d of age (TRT300). Administration of exogenous bST continued until all animals reached 400 d of age. Therefore, the duration of treatment for each group was 200, 150, and 100 d for TRT200, TRT250, and TRT300, respectively. The fourth group served as controls and did not receive any bST. Thus, to determine the effect of bST treatment in each age group, data from bST-treated animals in each treatment group were compared with data from animals of the control groups during the same time frame (contemporary controls).
All animals were weighed on 2 consecutive days each week starting 2 wk before bST injections. Backfat thickness and LM area (LEA) were measured using ultrasonography in all animals at 200, 250, 300, 350, and 400 d of age. Measurements were taken at the intercostal space between the 12th and 13th ribs, approximately 10 cm lateral to the spine (Tripp et al., 1998). Ultrasound images in duplicate were digitally stored until analyzed. Each image was measured twice, and the mean values of the duplicates were used for statistical analysis. Serum was harvested by centrifugation (1,800 x g) from blood samples collected from each animal via jugular venipuncture at 200, 250, 300, 350, and 400 d of age. Three samples of jugular blood (10 mL; 30 min apart) from each animal were collected on each day of sampling to minimize the effects of the pulsatile nature of ST secretion (Gluckman and Breier, 1987).
Serum Analyses
Serum concentrations of ST and IGF-I were determined by RIA. Serum ST was quantified in all samples (Kazmer et al., 1992). Antiserum to ST (NIDDK anti-oST2; AFP-C0123080 antibody, provided by A. F. Parlow) was used at a dilution of 1:20,000. Intra- and interassay CV averaged 10.5 and 10.8%, respectively, for control sera (15.8 ng/mL). Concentrations of IGF-I were determined for each animal from 1 serum sample collected on each sampling day. Briefly, unbound IGF-I was extracted by removing the acid-labile subunit and IGFBP by using the glycylglycine hydrochloric acid (0.2 M glycylglycine, pH 2.1; ICN Biomedicals, Aurora, OH) extraction method (Govoni et al., 2002). Antiserum to IGF-I (antihIGF-1 antibody, provided by A. F. Parlow) was used at a dilution of 1:500,000. The amount of 125I-IGF-I (Amersham Biosciences, Piscataway, NJ) added was adjusted so that each tube contained 10,000 cpm. The intra- and interassay CV averaged 6.8 and 18.3%, respectively, for control sera (75.1 ng/mL). The lower limits of sensitivity for the ST and IGF-1 assays were 1.0 and 20 ng/mL, respectively.
A ligand blot technique, previously described by Freake et al. (2001) and Govoni et al. (2002, 2003), was used to determine the concentrations of IGFBP-2 and -3 in 1 serum sample from each sampling day (for a total of 5 samples/animal). Briefly, molecular weight markers (BioRad, Richmond, CA), recombinant hIGFBP-3 (8 ng; Diagnostic Systems Laboratories, Webster, TX) as a control, and 6 serum samples (1 µL) were run in 8 lanes on a Mini Protean II (BioRad) and then transferred to a nitrocellulose membrane. To randomize the samples across gels (67 gels in total), at least 1 sample from each of the 4 groups and at least 1 sample from each of the 5 sampling days was included in each gel. Membranes were incubated overnight with approximately 1.6 MBq of 125I-labeled IGF-I (Amersham). Membranes were then exposed to a multipurpose phosphor screen (Packard Instrument Company, Meriden, CT), and bound radioactivity on each blot was quantified with a Cyclone Storage Phosphor System (Packard). Images were analyzed with OptiQuant acquisition and analysis software (Packard). Each binding protein was measured as digital light units/mm2. Each band was measured twice per gel, and the 4 measurements for each sample were averaged. Data are expressed as arbitrary units (AU).
Statistical Analyses
A randomized complete block design was used with 4 treatments in 4 blocks. Statistical analysis was performed using the MIXED procedure (SAS Inst. Inc., Cary, NC). For BW, ADG, and G:F over time, the model included treatment, breed, sex, week, treatment x breed, treatment x sex, and treatment x week; week was defined as the repeated variable. For ST, IGF-I, IGFBP-2, and IGFBP-3, the final model included treatment, breed, sex, sampling time, treatment x breed, treatment x sex, and treatment x sampling time interactions. The repeated variable was sampling time.
|
RESULTS |
|---|
|
TopAbstractINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
). No difference was observed between breeds (P = 0.67), whereas males gained more (P < 0.01) than females (215.5 ± 3.8 vs. 196.6 ± 3.7 kg), but there was no treatment x sex interaction (P = 0.57). Overall, average DMI was reduced 13.6% (P < 0.05) in bST-treated cattle compared with control animals. This decrease in DMI, coupled with increased BW gain, resulted in greater (P < 0.05) mean efficiency of gain in bST-treated animals (11.7, 14.0, and 26.4% greater in TRT200, TRT250, and TRT300, respectively), compared with controls of the same timeframe (data not shown).
|
Components of the Somatotropic Axis
At the beginning of the experiment, serum ST concentrations of all animals averaged 14.9 ± 2.0 ng/mL and no differences (P = 0.50) were observed between the 4 groups of animals. There was no effect of breed (Angus vs. Hereford; P = 0.80) or sex (male vs. female; P = 0.90), and therefore data were combined. There was an age-dependent decrease (P < 0.05) in the concentration of ST in all animals, regardless of treatment. Relative to contemporary controls, there was no difference (P = 0.30) in concentrations of bST in the samples collected just before the initiation of bST treatment in each treatment group (Figure 2). However, relative to controls, bST treatment increased (P < 0.01) serum ST concentrations in all age groups by d 50 of treatment (Figure 2).
|
). Concentrations of IGF-I did not differ between sexes (P = 0.23) or breeds (P = 0.34); therefore, the data were combined. Overall, from 200 to 400 d of age, IGF-I concentrations increased (P < 0.01) from 153.7 ± 17.9 to 352.3 ± 97.6 ng/mL. Relative to contemporary controls, there was no difference (P = 0.68) in concentration of IGF-I in the samples collected just before the initiation of bST treatment (Figure 3). Exogenous bST administration increased (P < 0.01) concentrations of IGF-I compared with contemporary control animals within 50 d of treatment in all treatment groups. Serum concentrations of IGF-I were similar (P = 0.20) across the bST-treated groups following administration of bST (Figure 3).
|
). No difference in IGFBP-3 concentration was observed between breeds (P = 0.82) or sex (P = 0.98), so the data were combined. Overall, treatment with bST increased (P < 0.01) concentrations of IGFBP-3 such that average IGFBP-3 concentrations at the end of the experiment were greater (P < 0.01) in the bST-treated animals compared with control animals (1275.4 ± 157.2 vs. 246.2 ± 178.0 AU). Concentrations of IGFBP-3 in TRT200 animals were similar (P = 0.30) to controls after 50 d of bST treatment but were greater (P < 0.01) after 100, 150, and 200 d of bST treatment. In addition, relative to the start of bST treatment in TRT200 cattle, bST-induced increases in IGFBP-3 were not observed until 100 d of treatment (d 0 vs. 50: P = 0.20; d 0 vs. 100: P < 0.01). In contrast, bST- induced increases in TRT250 and TRT300 were observed (P < 0.01) after 50 d of treatment (Figure 4).
|
). Overall, there was no effect of sex (P = 0.74), but Angus cattle had greater (P < 0.01) IGFBP-2 concentrations than Hereford cattle (437.2 ± 40.0 vs. 276.0 ± 37.0 AU).
|
|
DISCUSSION |
|---|
|
TopAbstractINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
), and the response to exogenous ST begins as early as 1 d of age in beef cattle (Govoni et al., 2004). However, ST has minimal effects during the early stages of life (Campbell et al., 1991). Therefore, maturation of the somatotropic axis is a major factor in the ontogeny of growth regulation. For example, we previously reported that the response of the somatotropic axis to exogenous bST was greater in older and heavier calves (Rausch et al., 2002). Similarly, little effect of ST treatment was observed in prepubertal mice, in terms of growth rate, compared with pubertal and postpubertal mice (Kasukawa et al., 2003). In addition, increased growth response in bST-treated beef cattle was associated with an increase in IGFBP-3 and a decrease in IGFBP-2 concentrations at 250 d of age (Govoni et al., 2004). Based on these data, we hypothesized that at a specific age between 200 to 400 d of age, beef cattle would produce a maximum growth response to a dosage of exogenous bST administration that has been effective in increasing BW (Moseley et al., 1992; Tripp et al., 1998; Rausch et al., 2002). In addition, we postulated that bST-induced increments in BW gain would be associated with increased concentrations of ST, IGF-I, and IGFBP-3, and reduced concentrations of IGFBP-2. To test this hypothesis, we determined growth rate, the efficiency of gain, and measures of components of the somatotropic axis (ST, IGF-I, IGFBP-2, and IGFBP-3) in beef cattle administered exogenous bST at different ages, starting at 200, 250, and 300 d, and continuing until all the animals reached 400 d of age.
Similar to previous reports, growth rate was improved in animals treated with daily injections of exogenous bST beginning at 200, 250, and 300 d of age (Schwarz et al., 1993; Tripp et al., 1998). In addition to increased BW gain, administration of bST improved the efficiency of gain (Enright et al., 1990; Schwarz et al., 1993; Holzer et al., 1999). In agreement with our hypothesis, BW gain and the efficiency of gain during the treatment period were greatest in cattle that began bST treatment at 300 d of age. This increased response to bST in a shorter time frame is likely due the fact that these animals began bST treatment at an older age and were heavier at the start of treatment compared with animals in the TRT200 and TRT250 groups (McShane et al., 1989; Rausch et al., 2002). Therefore, in terms of growth rate and the efficiency of gain, these beef cattle were more responsive to bST when treatment began at approximately 300 d of age.
Surprisingly, the magnitude of bST-induced increases in BW was less in the TRT250 group than the other 2 treatments. There was a reduction in DMI in all animals between wk 6 to 9 of the experiment, which slowed growth rate in all animals. This is the same time frame when bST treatment began in the TRT250 group. Thus, the reduction in nutrient intake may have reduced the bST responsiveness of the TRT250 group (Vicini et al., 1991; Rausch et al., 2002). Unfortunately, we do not have any blood samples to evaluate the hormonal response to bST during this period of reduced DMI.
Administration of bST decreased the accumulation of subcutaneous fat as measured by ultrasound in the current report. These data are in agreement with those of Schwarz et al. (1993), Radcliffe et al. (1997), and Holzer et al. (1999), indicating that treatment with bST reduces carcass fat. Although bST has been shown to increase carcass protein (Radcliffe et al., 1997), in agreement with Moseley et al. (1992) and Rausch et al. (2002), no difference in ultrasound measurement of LEA in bST-treated animals was detected in the current study.
As expected, administration of bST increased serum concentrations of ST. This increase occurred for the duration of treatment, but the magnitude of increase declined after 350 d of age as previously reported (Rausch et al., 2002; Govoni et al., 2004). In agreement with Govoni et al. (2004), serum concentrations of ST were similar in males and females following bST administration, which could be attributed to castration in males. Testosterone increases serum ST concentration by minimizing the feedback inhibition on ST secretion (Veldhuis et al., 2005), whereas in castrated males the effect of testosterone is minimized.
Similar to previous studies, daily administration of exogenous bST (33 µg of bST/kg of BW) increased serum concentrations of IGF-I relative to controls (Tripp et al., 1998; Rausch et al., 2002). The changes in serum IGF-I concentrations in bST-treated animals paralleled changes in concentrations of ST.
In control animals, IGFBP-3 concentration increased from 200 d of age to 300 d of age and then began to decline. Similar age-related changes in the IGFBP-3 concentrations have been reported in cattle (Skaar et al., 1994; Govoni et al., 2003) and pigs (Harrell et al., 1999). However, the age-related decline in IGFBP-3 concentrations was not observed in bST-treated animals. Serum concentrations of IGFBP-3 were increased following administration of bST. The bST-induced increase in IGFBP-3 was observed within 50 d (i.e., at the next sampling day) of the initiation of treatment in the TRT 250 and TRT 300 groups. However, bST-induced increases in IGFBP-3 were observed only after 100 d in cattle that began treatment at 200 d of age, indicating that the response of IGFBP-3 to exogenous bST was delayed in younger animals. Similarly, bST did not stimulate IGFBP-3 in beef calves less than 250 d of age and treated with bST from birth to 1 yr of age (Govoni et al., 2004).
The age-related decrease in serum IGFBP-2 concentrations was consistent with previous reports (Vicini et al., 1991; Cohick et al., 1992; Govoni et al., 2003, 2004). Similar to previous reports, this age-related decrease was greater in bST-treated animals than their contemporary controls (Radcliffe et al., 1997; Rausch et al., 2002) and serum concentrations of IGFBP-2 were negatively associated with increased growth rate (Radcliffe et al., 1997). In agreement with Govoni et al. (2004), there were no differences in IGFBP-2 observed between male and female cattle treated with bST. However, Angus cattle had greater IGFBP-2 concentrations compared with Hereford cattle, which confirms previous data (Jones et al., 2004), suggesting variation in IGFBP among different breeds.
Based on the data in the current study that serum concentrations of IGF-I and IGFBP-3 are elevated following treatment with bST, it appears that ST is working through stimulating IGF-I and IGFBP-3 in the circulation. Although it is well established that ST stimulates IGF-I from the liver, it is also possible that GH may also be working directly on target tissues, such as muscle and adipose, to stimulate local IGF-I or IGFBP-3 action, or both, and that the magnitude of these direct actions of ST on IGF, IGFBP, or both are related to age. For example, IGF-I-dependent actions of ST are greater in pubertal and postpubertal mice compared with prepubertal mice (Mohan et al., 2003). Consistent with our results, Kasukawa et al. (2003) reported that growth response to ST treatment was age dependent with the greatest response occurring in pubertal and postpubertal mice and the least response in prepubertal animals. In mice, these data may indicate that IGF-dependent effects of ST are responsible for increases in growth rate. Our findings are consistent with these findings in mice and indicate that older calves are more responsive to exogenous ST treatment due to increased responsiveness of IGF-I to ST at the older age. Further study is needed to determine whether exogenous ST treatment in beef cattle stimulates local action of IGF-I as well as systemic IGF-I in an age-dependent mechanism.
In summary, daily injections of exogenous bST increased BW and the efficiency of gain. In agreement with our hypothesis, the magnitude of the BW and the efficiency of gain response to bST treatment was greater in the older group of animals used in the current study. Relative to controls, these changes were associated with increased serum concentrations of ST, IGF-I, and IGFBP-3 and decreased concentration of IGFBP-2. The relatively slower growth rate of the younger animals was coupled with a delayed bST-induced increase in IGFBP-3; thus the magnitude of bST-induced change in IGFBP-3 may be a good indicator of the response to bST (Govoni et al., 2004). Based on these data, we conclude that bST administration should begin around 300 d of age for increased efficiency of gain in beef cattle.
|
Footnotes |
|---|
2 Current address: Department of Dairy Science, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.
3 Current address: Musculoskeletal Disease Center at the Jerry L. Pettis VA Medical Center, Loma Linda, CA 92357.
4 Corresponding author: steven.zinn{at}uconn.edu
Received for publication May 18, 2007. Accepted for publication August 9, 2007.
|
LITERATURE CITED |
|---|
|
TopAbstractINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
This article has been cited by other articles:
|
|
 |
|
  P. M. Yamada and K.-W. Lee Perspectives in mammalian IGFBP-3 biology: local vs. systemic action Am J Physiol Cell Physiol, May 1, 2009; 296(5): C954 - C976. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
