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ANIMAL GROWTH, PHYSIOLOGY, AND REPRODUCTION |
Department of Animal Science, University of Connecticut, Storrs 06269-4040
Abstract
Administration of exogenous bovine ST (bST) increases growth rate, feed efficiency, and carcass quality in beef cattle. The magnitude of response to bST in beef cattle is variable and related to the age of the animal. Our objective was to determine the response of the somatotropic axis, in particular IGF-I, IGFBP-2, and IGFBP-3, to bST treatment from birth to 1 yr of age. Blood samples were collected before and after a single injection of bST (500 mg) every 50 d from birth to 1 yr of age in male and female Hereford calves. Body weights and serum concentrations of ST, IGF-I, IGFBP-2, and IGFBP-3 were determined. At birth, serum concentrations of ST, IGF-I, and IGFBP-3 increased (P < 0.05) following bST treatment. From 50 to 350 d of age, average concentrations of ST and IGF-I were greater (P < 0.05) in males, whereas IGFBP-2 concentrations were greater (P < 0.05) in females. No gender differences in IGFBP-3 concentrations were observed. Following bST treatment, IGF-I increased (P < 0.05) from 50 to 350 d of age, IGFBP-2 decreased (P < 0.05) from 50 to 200 d of age, and IGFBP-3 increased (P < 0.05) at 250 d of age. At 250 d of age, baseline concentrations of IGFBP-2 decreased (P < 0.05). Due to the positive response of IGFBP-3 and decreased baseline IGFBP-2 at 250 d of age, we conclude that this is an age at which the somatotropic axis is most responsive to exogenous bST, and it therefore may be an appropriate age to begin bST treatment in beef calves to realize the positive influence of bST on BW gain, feed efficiency, and carcass composition.
Key Words: Bovine • Insulin-Like Growth Factor-I • Insulin-Like Growth Factor-Binding Proteins • Somatotropic Axis • Somatotropin
Introduction
Administration of exogenous ST influences the somatotropic axis and improves BW gain, feed efficiency, and carcass composition in cattle (Moseley et al., 1992
; Rausch et al., 2002). However, bovine ST (bST)-induced increases in BW gain are variable, ranging from 0 to 45% (Dalke et al., 1992; Houseknecht et al., 1992) compared with controls.
Several factors, such as nutrition, age, and size of treated animals at the start of the experiment, may be responsible for this variation (McShane et al., 1989; Rausch et al., 2002). For example, with restricted feeding, response to ST is diminished (Rausch et al., 2002) or abolished (Kriel et al., 1992) in cattle and lambs, respectively. Younger cattle that have not yet attained 300 kg of BW did not respond to bST, but bST increased BW gain in older (greater than 300 kg BW) cattle (Rausch et al., 2002). Compared with younger cattle, increased BW gain in the older cattle was associated with greater bST-induced increases in IGFBP-3 and decreases in IGFBP-2. Thus, bST-induced changes in IGFBP may occur later in development, causing younger animals to be less responsive to bST than older cattle. Similarly, in terms of IGF-I, 37-d-old pigs did not respond to exogenous porcine ST (pST), but responsiveness to pST increased with age (Harrell et al., 1999), indicating that animals may be more responsive to bST administration at specific ages, which may be correlated with age-related changes in the somatotropic axis (Govoni et al., 2002). Because serum ST, IGF-I, IGFBP-3, and IGFBP-2 are associated with changes in BW and bST treatment (Rausch et al., 2002; Govoni et al., 2003), examination of the response of these components of the somatotropic axis will provide better understanding of our previously reported age-related response to bST (Rausch et al., 2002). Therefore, the objective of this experiment was to determine the ontogeny of the response of components of the somatotropic axis from birth to 1 yr of age in Hereford cattle treated with exogenous bST.
Materials and Methods
Animals
A total of 16 male and 12 female Hereford calves, born within 9 wk of each other, was used. Calves were housed unrestrained and with their dams in covered pens (225 m2) with constant access to an exercise yard (525 m2) for 1 wk postpartum. Samples were collected from all calves at birth. Following sample collection and bST challenge at birth, the first 20 calves born (10 males and 10 females; born within 4 wk of each other) remained on the study, and the other eight calves were returned to the herd. Calves were maintained and fed as previously described (Govoni et al., 2003). Briefly, following the first week of life, the 20 calves and dams remained in pens and were fed (as-fed basis) grass:corn (30:70) silage with a 16% CP supplement (70 Mcal of ME), mixed daily. At 4 to 8 wk of age, calves and dams were maintained on grass pasture (improved New England native pasture). Beginning at 8 to 12 wk of age, calves had access to a creep feeder (16% CP; 70 Mcal ME) when on grass pasture. All male calves were castrated (125 ± 15 d of age) using a bloodless castration system (EZE bloodless castrator, Wadsworth Mfg. Inc., St. Ignatius, MT). At weaning (184 ± 15 d of age), calves were returned to the covered pens and fed (as-fed basis) a corn:grass (50:50) silage, supplemented with a 40% soybean-based protein supplement (1 kg•animal–1•d–1) formulated for calves to gain 1.2 kg/d (NRC, 1996). When housed in covered pens, calves were fed at 0730. Water was available ad libitum. The animal use protocol for this experiment was approved by the Institutional Animal Care and Use Committee at the University of Connecticut.
Sample Collection and bST Challenge
Ten-milliliter blood samples were collected by jugular venipuncture at eight different periods beginning at birth (Period 1) and every 50 d until 350 d of age (Periods 2 to 8). These periods were determined based on certain physiological and management time points determined in a previous experiment (Govoni et al., 2003). At birth, three samples were collected at 30-min intervals within 24 h following birth. Following collection of the third sample, bST (500 mg of Posilac, Monsanto Co., St. Louis, MO) was injected in the tailhead of seven males and seven females (nine males and five females were not injected and used as controls). Following bST treatment, blood samples (three samples, 30-min intervals) were collected at 1, 3, 5, and 7 d of age.
For Periods 2 to 8, the males (n = 7) and the females (n = 7) treated with bST at birth, as well as six control animals (three males and three females) were used. Treated animals were given a single injection of bST (500 mg of Posilac) in the tailhead at each period, whereas controls were not injected. For Periods 2 to 8, blood samples were collected at –7, –6, –4, –2, 0, 1, 3, 5, and 7 d relative to bST administration. On each sampling day, for all periods, three samples were collected at 30-min intervals. The calves used in this experiment followed the normal management practice of the University of Connecticut beef barn. Therefore, as the animals aged, their diets changed. However, at each time point that the animals were challenged with bST, samples were collected before and after treatment. Therefore, the change in diet over time does not affect the response to bST treatment at each period. To determine whether there was a residual effect of bST treatment between periods, samples were collected from the six control animals (three males and three females) at each period and compared with the samples taken before bST treatment of the treated animals at each period. There was no significant difference between BW and average concentrations of ST, IGF-I, and IGFBP-3 between treated and control animals. Although there was a significant treatment x period interaction (P = 0.01) for IGF-I, concentrations of IGF-I were not different between control and treated calves at each period. There was a significant treatment (P = 0.05) and treatment x period interaction (P = 0.02) for concentrations of IGFBP-2. However, this was only significant for Periods 2 to 4, and at these periods, concentrations of IGFBP-2 were greater in treated than control calves. Because we have previously reported a decrease in concentrations of IGFBP-2 following bST injection (Rausch et al., 2002), we do not believe this difference is due to a residual effect of the single bST treatment given at each period. Therefore, there was no residual effect of the bST treatment observed that affected the results, and the data presented for Periods 2 to 8 are for the 14 treated animals. For Periods 2 to 8, concentrations of ST, IGF-I, IGFBP-2, and IGFBP-3 were compared before and after bST treatment at each period, such that the seven males and the seven females that were treated served as their own controls. Data for the samples taken before bST administration (d –7, –6, –4, –2, and 0) were averaged together and expressed as pre-bST, and samples taken following bST administration (d 1, 3, 5, and 7) were averaged together and expressed as post-bST. Body weights were taken at birth and 7 d of age during Period 1 and three times (d –7, 0, and 7 relative to bST administration) during Periods 2 to 8.
Serum Analysis
Serum concentrations of ST and IGF-I were determined by RIA. Serum ST was quantified in all serum samples (Kazmer et al., 1992). Antisera to ST (NIDDK anti-oST2; AFP-C0123080 antibody, provided by A. F. Parlow) were used at a dilution of 1:20,000. Intraassay and interassay CV averaged 15.1 and 20.7% for low (32.0 ng/mL) and 12.1 and 15.4% for high (79.2 ng/mL) pools, respectively. Concentrations of IGF-I were determined for each animal from one serum sample collected each sampling day (Govoni et al., 2002). Antisera to IGF-I (rabbit-anti-hIGF-I antibody, provided by A. F. Parlow) were used at a dilution of 1:500,000. Intraassay and interassay CV averaged 7.4 and 7.0% for low (366 ng/mL) and 13.0 and 15.2% for high (414 ng/mL) pools, respectively.
Serum IGFBP-2 and -3 were determined using western ligand blot (Freake et al., 2001) in one sample from each day in Period 1 and from one sample on d –4, 0, 1, 3, 5, and 7 of Periods 2 to 8. Briefly, molecular weight markers (BioRad, Richmond, CA), recombinant human IGFBP-3 (8 ng; Diagnostic Systems Laboratories, Webster, TX) and six serum samples (1 µL) were run in eight lanes on a Mini Protean II (BioRad) and then transferred to a nitrocellulose membrane. Each gel was run in duplicate. Membranes were incubated overnight with approximately 1.6 MBq of 125I-labeled IGF-I (Amersham Pharmacia Biotech, Piscataway, NJ). Membranes were then exposed to a multipurpose phosphor screen (Packard Instrument Co., 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). To account for gel-to-gel variation, each binding protein was measured as digital light units/mm2 and calculated as a percentage of the signal of the standard IGFBP-3 included on each gel. Each band was measured twice per gel, and the four measurements for each sample were averaged together. Data are expressed as arbitrary units (AU).
Statistical Analysis
Statistical analysis was performed using the MIXED model ANOVA procedure of SAS (SAS Inst., Inc., Cary, NC), and a significant difference was determined as P 
0.05. Eight covariance structures (compound symmetry, heterogenous compound symmetry, first-order autoregressive, heterogeneous autoregressive, toepliz, heterogeneous toepliz, first-order ante-dependence, and unstructured) were examined. A goodness of fit statistic was used to determine which covariate adequately fit the data. The Kenward-Roger procedure was selected to determine the denominator degrees of freedom. Variance components for all analyses were estimated using restricted maximum-likelihood method. All data are expressed as least square means ± SE.
For BW and ADG over time, treatment, gender, period, treatment x gender, treatment x period, gender x period, and treatment x gender x period interactions were included in the final model. The subject used in the repeated statement was animal within gender, and the repeated variable was period. The covariate model used was first-order ante-dependence. For ST, IGF-I, IGFBP-2, and IGFBP-3 at birth, the final model included treatment, gender, day, treatment x gender, treatment x day, gender x day, and treatment x gender x day interactions. The subject used in the repeated statement was animal within gender and the repeated variable was day. The covariate model used was compound symmetry, first-order autoregressive, heterogeneous compound symmetry, and heterogeneous autoregressive for ST, IGF-I, IGFBP-3, and IGFBP-2, respectively.
To determine whether there was a residual effect of bST treatment between each period, the compound symmetry covariate model was used for all pre-bST treatment samples in the control and treated calves. The final model included treatment, gender, period, treatment x gender, treatment x period, gender x period, and treatment x gender x period interactions. The subject used in the repeated statement was animal within gender, and the repeated variable was period. Because there was no residual effect of the bST treatment, only the data for the bST-treated calves (n = 14) were analyzed for Periods 2 to 8.
Comparison of pre-bST samples between treated and control calves from birth to 350 d of age indicated that there was no significant residual effect of a single injection of bST on the following period. Therefore, a single injection of bST, 50 d before sampling was not the cause of changes observed over time in the pre-bST samples. This was expected because, in dairy cattle, Posilac (the formulation of bST used in this experiment) must be administered every 2 wk to maintain sufficient concentrations of ST to increase milk production (Eppard et al., 1991). Thus, the changes observed over time in the current experiment are not related to the prior bST treatment and therefore, the data from each period may be analyzed individually.
Each calf, at each period, was administered a set dose of bST (500 mg of Posilac). Therefore, to account for the change in BW over the course of the experiment, data for ST, IGF-I, IGFBP-3, and IGFBP-2 were adjusted for dose (500 mg/kg BW) using covariate analysis. Based on these analyses, there was no significant effect of dose for IGF-I, IGFBP-3, and IGFBP-2. Therefore, the changes reported over time and the response to bST treatment are independent of the dose administered. The term response refers to the change in concentration between pre-bST and post-bST treatment samples following adjustment for dose. For Periods 2 to 8, the compound symmetry covariate analysis was used for ST, IGF-I, IGFBP-3, and IGFBP-2. The final model included dose, gender, period, and time (pre-bST treatment vs. post-bST treatment), gender x period, gender x time, period x time, and gender x period x time interactions. The subject used in the repeated statement was animal within gender, and period was the repeated variable.
Results
Body weights increased (P < 0.01) from birth to 1 yr of age (45 ± 1 to 440 ± 8 kg; data not shown), but averaged across all time points, BW were not different between males and females (243 ± 8 vs. 233 ± 8 kg). Average daily gain was not different between males and females except at 200 d of age, when ADG was greater (P < 0.05) in males than in females (1.39 ± 0.04 vs. 1.26 ± 0.04 kg/d, respectively).
Response to Exogenous bST Treatment at Birth
In baseline samples taken within 24 h following birth, there was no difference between males and females or between treated and control animals for serum concentrations of ST, IGF-I, and IGFBP-3 (Figure 1). In addition, average concentrations from samples between birth and 7 d of age for treated and control animals were not different between males and females for ST (62.0 ± 8.6 vs. 51.0 ± 10.0 ng/mL), IGF-I (134 ± 17 vs. 162 ± 20 ng/mL), and IGFBP-3 (33 ± 3 vs. 41 ± 4 AU). Concentrations of IGFBP-2 were greater in females than in males (29 ± 2 vs. 22 ± 3 AU) between birth and 7 d of age (P = 0.05) due to elevated concentrations in control females at the sample taken within 24 h following birth.
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). Therefore, average concentrations of ST were greater (P < 0.001) in bST-treated than control calves between 1 and 7 d of age.
In control calves, concentrations of IGF-I decreased (P < 0.05) within 1 d following birth and then returned to birth concentrations by 3 d of age (Figure 1b). In bST-treated calves, concentrations of IGF-I increased within 24 h following bST treatment and continued to increase until 5 d of age. This resulted in greater (P < 0.01) concentrations of IGF-I in bST-treated versus control calves from 1 to 7 d of age (Figure 1b).
Concentrations of IGFBP-3 decreased in treated and control calves between birth and 1 d of age (P < 0.01), and then remained constant in control calves (Figure 1c). In bST-treated calves, concentrations of IGFBP-3 increased following 1 d of age such that concentrations of IGFBP-3 were greater (P < 0.05) in bST-treated than control calves from 3 to 7 d of age (Figure 1c).
At d 7 following bST treatment, there was no change in concentrations of IGFBP-2 in control males, whereas concentrations of IGFBP-2 in control females were variable (Figure 1d). Concentrations of IGFBP-2 decreased by 1 d of age following bST treatment in treated calves, and then returned to concentrations equal to those at birth by 3 d of age (Figure 1d).
Response to Exogenous bST at Periods 2 to 8
Between 50 and 350 d of age, average serum concentrations of ST in pre-bST treatment samples were greater (P < 0.01) in males than in females (11.7 ± 3.1 vs. 6.1 ± 3.1 ng/mL). In male calves, pre-bST treatment concentrations of ST decreased from 12.4 ± 3.1 ng/mL at 150 d of age to 6.4 ± 3.1 ng/mL at 250 d of age (P < 0.05; Figure 2a), whereas in female calves, pre-bST treatment concentrations of ST decreased from 5.0 ± 3.1 ng/mL at 200 d of age to 4.3 ± 3.1 ng/mL at 250 d of age (P < 0.05; Figure 2b). Serum concentrations of ST increased (P < 0.05) following bST treatment at all periods in males, and through 250 d of age in females. When adjusted for dose, the change in concentrations of ST following bST treatment was not different between males and females. In both males and females, with the adjustment for dose, there was a greater increase in concentrations of ST following bST treatment at 100 d of age than at 50 d of age (P = 0.02). This increase in concentrations of ST persisted through 250 and 350 d of age in males and females, respectively (P < 0.05).
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) and females (Figure 3b), respectively. There was no change in pre-bST treatment concentrations of IGF-I between 300 and 350 d of age, indicating the potential onset of a plateau. Overall, the bST treatment-induced increase in concentrations of IGF-I due to bST treatment was greater (P < 0.001) in females (Figure 3b) than in males (Figure 3a). There was no change in the magnitude of response to bST treatment from 50 to 150 d of age. For males and females, the greatest response to bST treatment was at 200 d (P < 0.05) of age, followed by a decrease (P < 0.05) in response from 200 to 300 d of age.
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). Over time, there was a decrease (P < 0.05) in pre-bST treatment concentrations of IGFBP-3 at 250 d of age (26 ± 7 AU). Male and female calves responded to bST treatment with an increase in IGFBP-3 at 250 d of age (P < 0.05). When adjusted for dose, the response was greater (P = 0.04) in males than females.
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) than in males (Figure 5b; 40 ± 2 vs. 34 ± 2 AU, respectively). Over time, in pre-bST treatment samples, concentrations of IGFBP-2 did not change from 50 to 200 d of age and decreased (P < 0.001) from 55 ± 4 at 200 d of age to 15 ± 4 at 250 d of age in all calves. From 50 to 200 d of age, bST treatment decreased concentrations of IGFBP-2 (P < 0.05) in males and females. There was a trend for a greater (P = 0.09) decrease in concentrations of IGFBP-2 in females than males. Following 200 d of age, the response to bST treatment was more variable and no significant effects were observed.
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Following a single injection of bST, concentrations of ST, IGF-I, and IGFBP-3 increased, and concentrations of IGFBP-2 decreased in male and females calves. We have previously reported similar changes in components of the somatotropic axis in cattle treated with daily injections of bST at a lower dose (33 µg/kg BW; Tripp et al., 1998; Rausch et al., 2002). In the current experiment, the age at which changes in these components of the somatotropic axis were observed varied and will be discussed subsequently.
Growth rates did not differ between males and females between birth and 350 d of age in these cattle. Previous reports indicate that males grow faster than females (Kerr et al., 1991; Gatford et al., 1996; Govoni et al., 2003). In this experiment, calves were castrated approximately 1 mo earlier than in our previous experiment (Govoni et al., 2003), but without determining concentrations of testosterone, we cannot be sure whether the time of castration had any effect on growth rate in these calves. Schwarz et al. (1992) also observed that BW were not different between heifers and steers between 205 and 306 kg; however, the age of these calves may not have been similar to those in the current experiment. As expected, there was no difference in growth rate associated with bST treatment in the current experiment due to the fact that we administered a single injection of bST every 50 d. It has been previously reported that at least three injections of Posilac are required to observe a change in milk yield in cattle (Eppard et al., 1999). Similar to lactation, continual treatment with bST is needed for a growth response to be observed in cattle (Holzer et al., 1999).
As expected, serum concentrations of ST increased following a single injection of bST in these calves. In addition, concentrations of IGF-I and IGFBP-3 increased within 1 and 3 d of bST administration, respectively, indicating that the somatotropic axis is responsive to exogenous stimulation as early as 24 h following birth. In young pigs administered pST, although not treated at birth, IGF-I and IGFBP-3 increased after 37 and 63 d of age, respectively (Harrell et al., 1999). Few studies have examined changes in IGFBP at or near birth in calves in response to exogenous bST administration. In addition, many of the changes observed in the somatotropic axis are in response to different physiological and nutritional challenges in young calves. For example, in Holstein calves at 6, 9, and 14 wk of age, concentrations of IGF-I and IGFBP-3 increased in response to a higher plane of nutrition (Smith et al., 2002). In the current study, concentrations of IGFBP-2 were variable following bST administration in newborn calves, but it has been reported that delayed feeding of colostrum in calves resulted in decreased concentrations of IGFBP-2 (Hammon et al., 2000). Therefore, at this young age, IGFBP-2 may be responsive to changes in physiological states, but may not be responsive to exogenous bST. For example, IGFBP-2 mRNA is greater in fetal liver development than in adult liver, and may have an important role in the perinatal period (Babajko et al., 1993). In addition, concentrations of IGFBP-2 decrease in growing animals (Skaar et al., 1994; Rausch et al., 2002). Therefore, the changing role of IGFBP-2 in the transition from fetal to postnatal development may explain why calves, in terms of IGFBP-2, do not respond to bST treatment at birth. Further work is needed to be able to determine the role of IGFBP-2 following bST treatment shortly after birth in calves.
In previous experiments, it has been reported that greater average concentrations of ST in males, compared with females, is due to a delayed age-related decrease in concentrations of ST (Schwarz et al., 1992; Govoni et al., 2003). In the current experiment, when evaluated from birth to 1 yr of age, there was a similar pattern, such that average concentrations of ST in the pre-bST treatment samples decreased sooner in the female calves from birth to 50 d of age (23 to 10 ng/mL) and from 100 to 150 d (19 to 12 ng/mL) of age than in the males. This resulted in greater average concentrations of ST in males than females during the first year of life.
Similar to previous reports in cattle (Ronge et al., 1989; Govoni et al., 2003), pigs (Clapper et al., 2000), and lambs (Gatford et al., 1996), there were greater average concentrations of IGF-I in pre-bST treatment samples in males than in females. It has been reported that concentrations of IGF-I plateau around 8 or 9 mo of age in Holstein cattle (Kerr et al., 1991; Govoni et al., 2002). Similar to our previous work in Hereford calves (Govoni et al., 2003), concentrations of IGF-I remained constant from 50 to 200 and 100 to 250 d of age in males and females, respectively. The variation in IGF-I observed in previous experiments may be due to differences between Holstein and Hereford cattle, as well as the relatively infrequent collection of blood samples. Based on our results, samples need to be collected more than once per month and for several consecutive months for specific age-related changes in the somatotropic axis to be identified.
We have developed two models of increased growth rate in cattle. In male calves (Govoni et al., 2003), as well as with daily bST injections (Rausch et al., 2002), increased growth rates have been reported. The increased growth rates in both of these models were associated with greater concentrations of ST, IGF-I, and IGFBP-3 and decreased concentrations of IGFBP-2 (Rausch et al., 2002; Govoni et al., 2003). In addition, increased concentrations of IGFBP-3 are associated with increased growth rates in rats (Freake et al., 2001). In the current experiment, pre-bST treatment concentrations of IGFBP-3 and growth rates were parallel (i.e., concentrations of IGFBP-3 and growth were similar between males and females). Thus, based on these data, concentrations of IGFBP-3 may be a good predictor of increased growth rate. Based on the correlation of a single measurement of serum IGFBP-3 with ADG, Conner et al. (2000) reported that IGFBP-3 is not as good a predictor of ADG as IGF-I. However, in serum, IGFBP-3 is found in tertiary complex with IGF-I and an acid-labile subunit (Jones and Clemmons, 1995). Therefore, due to this complex interaction between IGFBP-3, IGF-I, and acid-labile subunit, Conner et al. (2000) suggested that more than a single sample at one time point is needed to observe the predictive effect of IGFBP-3. Because changes in IGFBP-3 and growth rates are parallel in our previous (Freake et al, 2001; Rausch et al., 2002; Govoni et al., 2003) and current experiments, our results in growing calves and rats support the hypothesis of Mandel et al. (1995) that concentrations of IGFBP-3 may be a better indicator of growth rate than IGF-I.
At 250 d of age, pre-bST treatment concentrations of IGFBP-3 declined. In addition, at the same age in males and 50 d later in females, concentrations of IGF-I increased. In humans, treatment with exogenous IGF-I is associated with decreased concentrations of IGFBP-3 (Grinspoon et al., 2003). Therefore, the decrease in concentrations of IGFBP-3 in pre-bST treatment samples may be associated with increased concentrations of IGF-I observed in pre-bST treatment samples at the same time point.
Similar to a previous experiment (Govoni et al., 2003), there were greater average concentrations of IGFBP-2 in pre-bST treatment samples in females than in males. However, in the current experiment, concentrations of IGFBP-2 declined at a later age than previously reported (Govoni et al., 2003). This may be associated with increased concentrations of IGF-I in pre-bST treatment samples. For example, Grinspoon et al. (2003) reported that, in humans, IGF-I treatment for 3 mo resulted in increased concentrations of IGFBP-2. Therefore, increased IGF-I might be associated with the delayed decrease in concentrations of IGFBP-2.
Beginning at birth, concentrations of ST and IGF-I increased following bST treatment in male and female calves. When adjusted for dose, the response to bST treatment over time increased at 100 and 200 d of age for concentrations of ST and IGF-I, respectively. The age-related increase in the response of IGF-I to bST treatment at 200 d of age was similar to that previously reported for swine (Harrell et al., 1999). When concentrations of IGF-I in pre-bST treatment samples reached a plateau after 300 d of age, no additional changes in the magnitude of response to exogenous bST were observed. This plateau may indicate a time when changes in the somatotropic axis are less variable, and therefore the response to bST treatment may also be less variable beginning at this age.
Previous experiments have determined age- and size-related responses to exogenous ST in cattle (McShane et al., 1989; Rausch et al., 2002) and pigs (Harrell et al., 1999). However, concentrations of IGFBP were not determined in all of these experiments and/or sample collection was often infrequent and/or over short periods of time. Therefore, even though there was an increase in the response to bST treatment at 100 d of age, just examining changes in ST is not sufficient to determine the most effective age to begin administration of bST (Rausch et al., 2002). Examination of the response of IGFBP-2 and -3, in addition to ST and IGF-I, from birth to 1 yr of age provides a better understanding of the age-related changes in the somatotropic axis in response to bST treatment.
In males and females, the response of IGFBP-3 to bST treatment was only observed at 250 d of age. This may be associated with the decrease in concentrations of IGFBP-3 in pre-bST treatment samples. Similarly, Rausch et al. (2002) reported an age-related response to bST treatment in terms of growth rate at this age. Therefore, because IGFBP-3 is a better predictor of growth rate than IGF-I (Mandel et al., 1995), the increased IGFBP-3 may indicate the appropriate age to begin bST treatment in growing beef calves.
The decrease in concentrations of IGFBP-2 following bST treatment was similar to previous reports in cattle (Rausch et al., 2002). The response to bST treatment was greater at a younger age, which may be due to greater concentrations of IGFBP-2 in pre-bST treatment samples at these time points. When the calves were older, concentrations of IGFBP-2 decreased, so that the inhibitory response with bST treatment may not have been detectable (Rausch et al., 2002). Previous data (Rausch et al., 2002) indicate that calves are not responsive to bST treatment until they are older than 200 d of age. The data presented in the current experiment, with a response to bST treatment with an increase in IGFBP-3 and a decrease in baseline IGFBP-2 at 250 d of age may explain this age-related response to bST treatment. Because IGFBP-3 may be a better predictor of growth rate (Mandel et al., 1995), and IGFBP-2 is more important in fetal development (Babajko et al., 1993), we predict that 250 d of age would be an appropriate age at which to begin bST treatment to stimulate growth rate in beef cattle.
In summary, beginning at birth, there was a response to bST treatment in all components of the somatotropic axis that we measured. As previously reported (Rausch et al., 2002), quantification of concentrations of ST and IGF-I is not sufficient to determine age-related responses, in terms of growth rate, to bST treatment. Therefore, a closer examination of IGFBP-2 and -3 has provided a better understanding of the age-related response to bST treatment in growing beef cattle. Although concentrations of IGFBP-2 decreased following bST treatment from 50 to 200 d of age, Rausch et al. (2002) did not observe a response to bST treatment in terms of growth rate until calves were older than 200 d of age. At 250 d of age, concentrations of IGFBP-3 increased following bST treatment in these calves, and this is approximately the same age at which we previously reported an increase in growth rate in response to daily injections of bST. Therefore, these results indicate that administration of bST should begin at or after 250 d of age for increased growth rates to be observed. Further work with more frequent administration of bST beginning at 250 d of age, as well as examining changes in growth rate is needed.
Implications
The magnitude and efficacy of the response to bovine somatotropin in beef cattle is variable. In this experiment an age at which the somatotropic axis is more responsive to bovine somatotropin treatment has been identified. Therefore, more frequent administration of bovine somatotropin over a long period of time beginning at about 250 d of age may stimulate growth and increase the efficiency of production. Ultimately, this would be beneficial for the beef industry.
Footnotes
1 The authors thank E. Jones, D. Schreiber, and the personnel at the Univ. of Connecticut Cattle Teaching and Research Unit for assistance with sample collection and animal care. The authors thank G. Kazmer for his assistance with the bST RIA analysis. Posilac was kindly provided by Monsanto Co., St. Louis, MO. This research was supported by the Univ. of Connecticut Research Foundation and the Storrs Agric. Exp. Stn. 
2 Current address: Musculoskeletal Disease Center, Jerry L. Pettis VA Medical Center, Loma Linda, CA 92357.
3 Correspondence: 3636 Horsebarn Road Ext. (phone: 860-486-0861; fax: 860-486-4375; e-mail: szinn{at}canr.uconn.edu).
Received for publication November 26, 2003. Accepted for publication February 20, 2004.
Literature Cited
Babajko, S., S. Hardouin, B. Segovia, A. Groyer, and M. Binoux. 1993. Expression of insulin-like growth factor binding protein-1 and -2 genes through the perinatal period in the rat. Endocrinology 132:2586–2592.[Abstract]
Binelli, M., W. K. Vanderkooi, L. T. Chapin, M. J. Vandehaar, J. D. Turner, W. M. Moseley, and H. A. Tucker. 1995. Comparison of growth hormone-releasing factor and somatotropin: Body growth and lactation of primiparous cows. J. Dairy Sci. 78:2129–2139.[Abstract]
Boisclair, Y. R., Y. W. Yang, J. M. Stewart, and M. M. Rechler. 1994. Insulin-like growth factor-I and insulin stimulate the synthesis of IGF-binding protein-2 in a human embryonic kidney cell line. Growth Reg. 4:136–146.[Medline]
Clapper, J. A., T. M. Clark, and L. A. Rempel. 2000. Serum concentrations of IGF-1, estradiol-17ß, testosterone, and relative amounts of IGF binding proteins (IGFBP) in growing boars, barrows, and gilts. J. Anim. Sci. 78:2581–2588.
Conner, E. E., S. M. Barao, A. S. Kimrey, A. B. Parlier, L. W. Douglass, and G. E. Dahl. 2000. Predicting growth in Angus bulls: The use of GHRH challenge, insulin-like growth factor-I, and insulin like growth factor binding proteins. J. Anim. Sci. 78:2913–2918.
Dalke, B. S., R. A. Roeder, T. R. Kasser, J. J. Veenhuizen, C. W. Hunt, D. D. Hinman, and G. T. Schelling. 1992. Dose-response effects of recombinant bovine somatotropin implants on feedlot performance in steers. J. Anim. Sci. 70:2130–2137.[Abstract]
Eisemann, J. H., A. C. Hammond, T. S. Rumsey, and D. E. Bauman. 1989. Nitrogen and protein metabolism and metabolites in plasma and urine of beef steers treated with somatotropin. J. Anim. Sci. 67:105–115.
Eppard P. J., S. Hudson, W. J. Cole, R. L. Hintz, G. F. Hartnell, T. W. Hunter, L. E. Metzger, A. R. Torkelson, B. G. Hammond, and R. J. Collier. 1991. Response of dairy cows to high doses of a sustained-release bovine somatotropin administered during two lactations. 1. Production response. J. Dairy Sci. 74:3807–3821.[Abstract]
Freake, H. C., K. E. Govoni, K. Guda, C. Huang, and S. A. Zinn. 2001. Actions and interactions of thyroid hormone and zinc status in growing rats. J. Nutr. 131:1135–1141.
Gatford, K. L., T. P. Fletcher, I. J. Clarke, P. C. Owens, K. J. Quinn, P. E. Walton, P. A. Grant, B. J. Hosking, A. R. Egan, and E. N. Ponnampalam. 1996. Sexual dimorphism of circulating somatotropin, insulin-like growth factor I and II, insulin-like growth factor binding proteins, and insulin: Relationships to growth rate and carcass characteristics in growing lambs. J. Anim. Sci. 74:1314–1325.[Abstract]
Govoni, K. E., X. C. Tian, G. W. Kazmer, M. Taneja, B. P. Enright, A. L. Rivard, X. Yang, and S. A. Zinn. 2002. Age-related changes of the somatotropic axis in cloned Holstein calves. Biol. Reprod. 66:1293–1298.
Govoni, K. E., T. A. Hoagland, and S. A. Zinn. 2003. The ontogeny of the somatotropic axis in male and female Hereford calves from birth to one year of age. J. Anim. Sci. 81:2811–2817.
Grinspoon, S., K. Miller, D. Herzog, D. Clemmons, and A. Klibanski. 2003. Effects of recombinant human insulin-like growth factor (IGF)-I and estrogen administration on IGF-I, IGF binding protein (IGFBP)-2, and IGFBP-3 in anorexia nervosa: A randomized-controlled study. J. Clin. Endo. Metab. 88:1142–1149.
Hammon, H. M., I. A. Zanker, and J. W. Blum. 2000. Delayed colostrums feeding affects IGF-I and insulin plasma concentrations in neonatal calves. J. Dairy. Sci. 83:85–92.[Abstract]
Harrell, R. J., M. J. Thomas, R. D. Boyd, S. M. Czerwinski, N. C. Steele, D. E. Bauman. 1999. Ontogenic maturation of the somatotropin/insulin-like growth factor axis. J. Anim. Sci. 77:2934–2941.
Holzer, Z., Y. Aharoni, A. Brosh, A. Orlov, J. J. Veenhuizen, and T. R. Kasser. 1999. The effects of long-term administration of recombinant bovine somatotropin (Posilac) and Synovex on performance, plasma hormone and amino acid concentration, and muscle and subcutaneous fat fatty acid composition in Holstein-Friesian bull calves. J. Anim. Sci. 77:1422–1430.
Houseknecht, K. L., D. E. Bauman, D. G. Fox, and D. F. Smith. 1992. Abomasal infusion of casein enhances nitrogen retention in somatotropin-treated steers. J. Nutr. 122:1717–1725.
Jones, J. I., and D. R. Clemmons. 1995. Insulin-like growth factors and their binding proteins: Biological actions. Endocr. Rev. 16:3–34.[Medline]
Kazmer, G. W., S. A. Zinn, H. Rycroft, and R. M. Campbell. 1992. Serum growth hormone in and semen characteristics of proven AI dairy sires after administration of growth hormone-releasing factor. Can. J. Anim. Sci. 72:959–963.
Kerr, D. E., B. Laarveld, M. I. Fehr, and J. G. Manns. 1991. Profiles of serum IGF-I concentrations in calves from birth to eighteen months of age and in cows throughout the lactation cycle. Can. J. Anim. Sci. 71:695–705.
Kriel, G. V., M. J. Bryant, and M. A. Lomax. 1992. Effects of dietary protein intake and intravenous glucose infusion on plasma concentrations of insulin-like growth factor-I in lambs. J. Endocrinol. 132:195–199.
Mandel, S., S. Moreland, V. Nichols, C. Hanna, and S. Lafranchi. 1995. Changes in insulin-like growth factor-I (IGF-I), IGF-binding protein-3, growth hormone (GH)-binding protein, erythrocyte IGF-I receptors, and growth rate during ST treatment. J. Clin. Endorinol. Metab. 80:190–194.[Abstract]
McShane, T. M., K. K. Schillo, J. A. Boling, N. W. Bradley, and J. B. Hall. 1989. Effects of recombinant DNA-derived somatotropin and dietary energy intake on development of beef heifers. I. Growth and puberty. J. Anim. Sci. 67:2230–2236.
Moseley, W. M., J. B. Paulissen, M. C. Goodwin, G. R. Alaniz, and W. H. Claflin. 1992. Recombinant bovine somatotropin improves growth performance in finishing beef steers. J. Anim. Sci. 70:412–425.[Abstract]
NRC. 1996. Nutrient Requirements of Beef Cattle. 7th ed. Natl. Acad. Press, Washington, DC.
Peters, J. P. 1986. Consequences of accelerated gain and growth hormone administration for lipid metabolism in growing beef steers. J. Nutr. 116:2490–2503.
Preston, R. L., S. J. Bartle, T. R. Kasser, J. W. Day, J. J. Veenhuizen, and C. A. Baile. 1995. Comparative effectiveness of somatotropin and anabolic steroids in feedlot steers. J. Anim. Sci. 73:1038–1047.[Abstract]
Rausch, M. I., M. W. Tripp, K. E. Govoni, W. Zang, W. J. Weber, B. A. Crooker, T. A. Hoagland, and S. A. Zinn. 2002. The influence of level of feeding on growth and serum insulin-like growth factor-I and insulin-like growth factor binding proteins in growing beef cattle supplemented with somatotropin. J. Anim. Sci. 80:94–100.
Ronge, H., and J. W. Blum. 1989. Insulin-like growth factor I binding proteins in dairy cows, calves and bulls. Acta Endocrinol. 121:153–160.
Rumsey, T. S., T. H. Elsasser, S. Kahl, W. M. Moseley, and M. B. Solomon. 1996. Effects of Synovex-S and recombinant bovine somatotropin (Somavubove) on growth responses of steers: I. Performance and composition of gain. J. Anim. Sci. 74:2917–2928.[Abstract]
Schwarz, F. J., R. Ropke, D. Schams, and M. Kirchgessner. 1992. Effects of sex and growth on plasma concentrations of growth hormone, insulin-like growth factor-I and insulin in fattening Simmental cattle. J. Anim. Physiol. Anim. Nutri. 68:263–271.
Schwarz, F. J., D. Schams, R. Ropke, M. Kirchgessner, J. Kogel, and P. Matzke. 1993. Effects of somatotropin treatment on growth performance, carcass traits, and the endocrine system in finishing beef heifers. J. Anim. Sci. 71:2721–2731.[Abstract]
Skaar, T. C., C. R. Baumrucker, D. R. Deaver, and J. W. Blum. 1994. Diet effects and ontogeny of alterations of circulating insulin-like growth factor binding proteins in newborn dairy calves. J. Anim. Sci. 72:421–427.[Abstract]
Smith, J. M., M. E. Van Amburgh, M. C. Diaz, M. C. Lucy, and D. E. Bauman. 2002. Effect of nutrient intake on the development of the somatotropic axis and its responsiveness to GH in Holstein bull calves. J. Anim. Sci. 80:1528–1537.
Tripp, M. W., T. A. Hoagland, G. E. Dahl, A. S. Kimrey, and S. A. Zinn. 1998. Methionine and somatotropin supplementation in growing beef cattle. J. Anim. Sci. 76:1197–1203.
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