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Biology of Reproduction 66, 1293-1298 (2002)
© 2002 Society for the Study of Reproduction, Inc.

Regular Article

Age-Related Changes of the Somatotropic Axis in Cloned Holstein Calves1

Kristen E. Govonia, X. Cindy Tiana, Gary W. Kazmera, Maneesh Tanejaa, Brian P. Enrighta, Amber L. Rivarda, Xiangzhong Yanga, and Steven A. Zinn2,a

a Department of Animal Science, University of Connecticut, Storrs, Connecticut 06269


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
To determine if the development of the somatotropic axis in somatic clones (clones) is similar to that in heifers produced by artificial insemination (controls), serum samples were collected every 30 min for 6 h, once per month, for 7 mo from 4 clones generated from a 13-yr-old cow and from 4 age-matched controls. Average concentrations of growth hormone (GH) were not different between clones and controls, and GH concentrations declined over time in controls. Average concentrations of insulin-like growth factor I (IGF-I) were less in clones than controls, and IGF-I concentrations increased over time in both groups. Concentrations of IGF-binding protein 3 (IGFBP-3) were greater in controls than in clones and did not change over time. Average IGFBP-2 concentrations did not change over time and were not different between clones and controls. Clones and controls were challenged with GH-releasing hormone (GHRH) (3 µg/100 kg body weight) and somatostatin (somatotropin release-inhibiting factor [SRIF]) (1.87 and 5 µg/100 kg body weight) at 14 mo of age. GHRH-induced GH secretion was greater and SRIF inhibition of GHRH-induced GH was less in clones than in controls. We speculate that some of the differences between clones and controls in concentrations of GH, IGF-I, and IGFBP-3 may be related to the genetic merit of the animals. Although there were differences in concentrations of components of the somatotropic axis between these clones and their age-matched controls, the values recorded were all within the range reported for calves of similar ages.

developmental biology, embryo, growth hormone, reproductive technology


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The success of cloning a whole animal from a differentiated adult cell by somatic cell nuclear transfer [1] has been reported in mice [2–5], cattle [6–12], pigs [13], goats [14], and gaur [15]. The somatic cloning technology not only can be used to produce multiple copies of genetically elite animals or to regenerate tissue or organs for therapeutic cloning in biomedicine, but it is also an essential tool for basic research such as research on gene function and regulation of development. However, many developmental problems have been associated with nuclear transfer somatic cell clones. These problems include larger-than-normal calves and internal organs, high rates of fetal and postnatal mortality [16, 17], and abnormal immune function [18]. Furthermore, cloned animals have been reported to have shorter or longer telomeres than noncloned animals [4, 19–21]. All of these observations have raised the question of whether calves cloned using adult donor cells will develop normally as young calves.

Growth hormone (GH) is a metabolic hormone associated with growth rate, accretion of protein, metabolism of adipose tissue, and milk production in cattle and pigs [22]. The secretion of GH from somatotropes in the anterior pituitary gland is a central part of the somatotropic axis, which also includes the hypothalamus, the liver, and other target tissues [22]. Two hypothalamic peptides, GH-releasing hormone (GHRH) and somatostatin (somatotropin release-inhibiting factor [SRIF]) primarily regulate secretion of GH. GHRH, a 44-amino acid peptide, stimulates release of GH, whereas SRIF inhibits GHRH-induced GH secretion [23]. In cattle, the 28-amino acid form of SRIF, as opposed to the 14-amino acid form, is responsible for this inhibitory activity in vivo [24]. GH interacts with membrane receptors, particularly in the liver, but also in other target tissues, and stimulates the production of insulin-like growth factor I (IGF-I) [25]. IGF-I functions in endocrine, paracrine, and autocrine manners and mediates many of the effects of GH [26]. IGF-I acts through its own receptor to influence the growth and differentiation of numerous cell types. Six distinct IGF-binding proteins (IGFBPs) have also been described, which bind IGF with an affinity at least equal to those of the IGF receptors [26]. IGFBP-3 is the most abundant IGFBP and is responsible for transporting IGF-I in the blood. In addition, IGFBP-2 and IGFBP-3 are responsive to exogenous GH administration in cattle [27] and pigs [28]. Importantly, age-related changes in measures of the somatotropic axis have been reported in cattle [29] and pigs [28, 30]. Although there is quite extensive animal to animal variation, in general, as animals age, average serum concentrations of GH and serum IGFBP-2 decrease [29, 31], whereas serum concentrations of IGF-I and IGFBP-3 increase [28–30]. In Hereford calves studied from birth to 9 mo of age, we have reported a decrease in serum concentrations of GH and an increase in concentrations of IGF-I and IGFBP-3 [32].

To date, there have been no systematic studies on the normalcy of somatic clones, other than the length of telomeres, in terms of their development. Therefore, our objective was to determine if somatic clones develop similarly to age- and weight-matched calves. Given the age-related changes in the somatotropic axis, we compared concentrations of GH, IGF-I, IGFBP-2 and IGFBP-3, and concentrations of GH after GHRH and SRIF administration in 4 cloned heifers (clones) [12, 17, 33] with those of four age- and weight-matched heifers produced by artificial insemination (AI) (controls).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Animals

Four genetically identical cloned female calves, produced from a 13-yr-old Holstein cow of high milk production as previously described by Tian et al. [12], were used for this study. Of the 10 clones born alive, 4 survived (6 died within 24 h of birth). Therefore, we used the entire population of clones alive 24 h postpartum. In addition, an age- and weight-matched control Holstein calf (born within 14 days of its respective clone) for each of the 4 clones was also used in this study. All animals in clone and control groups were prepubertal at the start of the experiment (5–6 mo of age). To compare measures of the somatotropic axis in older animals at the beginning of the experiment, blood samples were also collected from postpubertal female Holstein calves (Postpubertal; n = 4; 11 mo of age) and the somatic cell donor cow (Aspen; 13 yr of age). The animal use protocol for this experiment was approved by the Institutional Animal Care and Use Committee at the University of Connecticut.

Sample Collection

Once per month for 7 consecutive months (5–11 mo of age), blood samples were collected from clones and controls via jugular catheters. Samples were collected from Postpubertal heifers and Aspen in the first 2 mo. On the morning of sample collection, animals were fitted with an indwelling cannula (Abbocath-T, 16-gauge x 140 mm; Abbott Laboratories, North Chicago, IL) in a jugular vein. Blood samples (10 ml) were collected every 30 min for 6 h (13 samples collected from each animal). Samples were stored at room temperature for 2–4 h and then stored overnight at 4°C. Serum was harvested from the cooled samples by centrifugation at 1800 x g (Sorval RT7; Kendro Laboratory Products, Newtown, CT) for 30 min and stored at -20°C until assayed.

GHRH and SRIF Challenge

GHRH (1–44 amino acids, G-0644; Sigma Chemical Company, St. Louis, MO) and SRIF (1–28 amino acids, S-6135; Sigma) were dissolved in sterile saline (0.9%) to concentrations of 10 and 5 µg/ml, respectively. At 14 mo of age, clones and controls were challenged with a bolus intravenous infusion of GHRH (3 µg/100 kg body weight [BW]) on 2 consecutive days at 0900 and 1200 h. Blood samples were collected at -60, -40, -20, 0, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, and 120 min relative to each administration of GHRH. In addition, animals were infused with SRIF (1.87 or 5 µg/100 kg BW) 2 min before the second GHRH administration (1158 h) on each day. To avoid confounding the effect of day with dosage, 2 animals in each group received the 1.87 µg SRIF dosage and 2 received the 5.0 µg SRIF dosage on the first day, and the alternate dosage was administered on the second day. Blood samples (10 ml) were collected and handled as described previously.

Serum Analysis

Serum GH was quantified in all serum samples [34]. Antisera to GH (National Institute of Diabetes and Digestive and Kidney Diseases anti-oGH2; AFP-C0123080 antibody, kindly provided by A.F. Parlow, National Hormone and Pituitary Program, Harbor-UCLA Medical Center, Torrance, CA) was used at a dilution of 1:20 000. Intraassay and interassay coefficients of variation for two serum pools (10.6 and 56.7 ng/ml) averaged 5.6% and 11.2%, respectively. We chose to quantify concentrations of IGF-I and not IGF-II because it has been reported that IGF-I is responsive to serum concentrations of GH [35]. Concentrations of IGFBP-3 were quantified because approximately 75% of circulating IGF-I is bound to the 150-kDa complex with IGFBP-3 and an acid-labile subunit (ALS) [26, 36]. We quantified concentrations of IGFBP-2 because they have been reported to be age-dependent and are often inversely related to concentrations of IGF-I [36, 37]. Concentrations of IGF-I were determined in two serum samples at each collection time from 5 to 11 mo and at 14 mo of age [38, 39]. All samples were quantified in a single assay with an interassay coefficient of variation of 4.8% (445 ng/ml) and 10.8% (200 ng/ml) for standard pools. Serum levels of IGFBP-2 and IGFBP-3 were determined using a Western ligand blot [40]. The data are expressed as arbitrary units and were calculated as a percentage of the signal of a standard IGFBP-3.

Data Analysis

Hormone data from serum samples (GH, IGF-I, and IGFBP-2 and IGFBP-3) collected from 5 to 11 mo of age and pre-GHRH infusion baseline samples (14 mo of age, samples 1–3) were analyzed using the Proc Mixed Model of Statistical Analysis Systems (SAS, version 8; SAS Institute, Inc., Cary, NC) [41] with repeated measures. GH data from GHRH and SRIF challenges were analyzed using the general linear model (GLM) procedure of SAS [41]. The model statement accounted for variation due to animal, sample, and dosage. Variance associated with animal by dosage was used to test for differences among dosages. Residual error was used to test for differences among samples. In addition, area under the response curve (AUC) was calculated, and areas were compared using the GLM procedures of SAS [41]. The model statement accounted for variation due to animal, period, dosage, and all interactions. Residual error (animal by period by dosage) was used to test for differences among period by dosage interactions. Data are reported as the mean ± the standard error of the mean (SEM).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Growth Hormone

Serum concentrations of GH are shown in Figure 1. Averaged across all time points, GH concentrations were not significantly different between clones (7.29 ± 0.96 ng/ml) and controls (5.50 ± 0.89 ng/ml). However, in controls, serum concentrations of GH decreased between 5 and 14 mo of age, but concentrations did not change in clones during the same time frame. Specifically, GH concentrations were greater in clones than in controls at 9, 10, and 11 mo of age, resulting in a treatment by time interaction (P < 0.01). As expected, GH concentrations in Postpubertal animals were less than those in prepubertal calves. Concentrations of GH in Postpubertal animals were less than those in controls at 5 mo of age and less than those in clones at 6 mo of age. However, when compared at similar ages (samples collected at 11 mo of age in clones and controls and at 12 mo of age in Postpubertal animals), GH concentrations were not different between Postpubertal animals and clones or controls. There were frequent pulses of GH in these clones and controls as would be expected in younger animals; however, the number of frequent pulses was not different between the two groups (Fig. 2). The pulsatile nature of GH secretion among animals contributed to the variation around average concentrations of GH within the clone and control groups.



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  		FIG. 1. Average growth hormone concentrations in clones, controls, and postpubertal (Postpubertal) animals. The pooled SEMs for 5–11 and 14 mo of age were 3.02 and 3.63 ng/ml for clones and controls, respectively. The pooled SEM for 11 and 12 mo of age was 1.48 ng/ml for Postpubertal animals



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  		FIG. 2. Individual animal GH secretion from either the first or the second month of sampling. A) Clone (6 mo of age). B) Control (6 mo of age). C) Postpubertal animal (11 mo of age). D) Aspen (13 yr of age)

GHRH and SRIF Challenges

To further investigate the difference in GH concentrations at 9, 10, and 11 mo of age between clones and controls, we conducted GHRH and SRIF challenges. Based on previous reports that the GH response to GHRH varies with genetic merit in cattle [42, 43] regardless of baseline concentrations of GH, we postulated that the greater concentrations of GH in clones were due to a greater responsiveness to GHRH and/or a reduced responsiveness to SRIF. Relative to pre-GHRH administration, GHRH induced a 15- and 10-fold increase of GH release in clones and controls, respectively, as early as 5 min after GHRH administration (P < 0.01). This increase in GH release lasted approximately 20 min, and by 40–50 min after GHRH infusion, GH returned to basal levels (Fig. 3). Whereas the 5-µg SRIF dosage completely inhibited the GHRH-induced increase of GH in both groups (data not shown), the level of inhibition of GHRH-induced GH secretion with the 1.87-µg SRIF dosage was less in clones than in controls (2- and 1-fold increases of GH release, respectively; P < 0.01; Fig. 4).



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  		FIG. 3. Concentrations of GH in clones and controls after GHRH (3 µg/100 kg BW) challenge using AUC analysis. The pooled SEM at 0–15 min was 232.69 ng·min/ml and at 15–30 min was 107.30 ng·min/ml



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  		FIG. 4. Concentrations of GH in clones and controls after GHRH and SRIF (1.87 µg/100 kg BW) challenge. SRIF was administered 2 min before GHRH. The pooled SEM at 0–15 min was 232.69 ng·min/ml and at 15–30 min was 107.30 ng·min/ml

Insulin-Like Growth Factor I

Overall, serum concentrations of IGF-I in clones and controls were parallel and increased over time from 5 to 14 mo of age. Changes in IGF-I concentrations in clone and control animals followed the same pattern, such that concentrations of IGF-I increased from 5 to 7 mo of age and exhibited a plateau from 7 to 11 mo of age (Fig. 5). Averaged across all time points, serum concentrations of IGF-I were less in clones than in controls (203.7 ± 13.8 vs. 306.4 ± 13.1 ng/ml; P < 0.001) from 5 to 11 and 14 mo of age (Fig. 5).



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  		FIG. 5. Average IGF-I concentrations in clones and controls. The pooled SEM for 5–11 and 14 mo of age was 33.50 and 34.39 ng/ml for clones and controls, respectively

IGF-Binding Proteins

Serum concentrations of IGFBP-3 paralleled IGF-I, such that, averaged across all time points, the IGFBP-3 concentration was less (P < 0.05) in clones than controls (Fig. 6). Concentrations of IGFBP-3 did not change over time in clones or controls. The average IGFBP-2 concentration did not change over time and was not different between clones and controls (Fig. 7).



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  		FIG. 6. Average IGFBP-3 concentrations in clones and controls. The pooled SEM for 5–11 and 14 mo of age was 10.30 and 13.57 AU for clones and controls, respectively



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  		FIG. 7. Average IGFBP-2 concentrations in clones and controls. The pooled SEM for 5–11 and 14 mo of age was 12.40 and 10.75 AU for clones and controls, respectively

For comparison purposes, the somatotropic axis was also monitored in the somatic cell donor of the clones. Data for the donor cow (Aspen) for the ages of 13 yr, 13 yr 1 mo, and 13 yr 10 mo, respectively, were GH (2.7, 10.0, and 6.0 ng/ml), IGF-I (152.4, 140.5, and 117.2 ng/ml), IGFBP-3 (50.4%, 51.9%, and 51.1%), and IGFBP-2 (35.4%, 43.1%, and 52.7%).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Somatic cloning is still a very challenging and low-efficiency technology. Since the birth of Dolly, the first cloned animal from an adult cell, only a handful of laboratories worldwide have reported successful effort in cloning using adult somatic cells. Furthermore, nearly all successful cloning efforts have been associated with low numbers of live births. This is mainly due to the fact that many cloned fetuses die during pregnancy and after birth. In our experience, up to 60% of somatic clones die within 24 h of birth [17]. Despite this high mortality rate, these clones used in this study were among the largest number of live clones reported at the time of their birth [6, 7, 11, 12]. Although the number is relatively low, this is by far one of the largest herds of clones from a single donor. They were born within a month of each other and represent identical copies of a potentially genetically superior cow from our research farm. Although there have been reports that telomere lengths are longer or shorter in clones [19], telomere length did not differ between the clones and controls in the present study [12].

Serum concentrations of GH (2–25 ng/ml), IGF-I (165–310 ng/ml), IGFBP-3 (60%–150%), and IGFBP-2 (65%–160%) in clone and control animals were in the range of data, in cattle of a similar age, previously reported by our laboratory [32, 44, 45]. Average GH concentrations during the entire experimental period were not different between clones and controls. Concentrations of GH in Postpubertal animals were less than those in clones and controls before puberty, and when Postpubertal animals were of a similar age to clones and controls (11–12 mo of age), concentrations of GH were not different. This is in agreement with previous reports that older animals have lower concentrations of GH when compared with younger animals [31]. Collectively, in terms of serum concentrations of GH, these clones exhibit developmental patterns appropriate for their age.

In this study, we observed that concentrations of GH in clones were greater than those in the controls at 9, 10, and 11 mo of age. To explain the difference between concentrations of GH in clones and controls at these ages, GHRH and SRIF, 2 hypothalamic factors that influence GH release, were administered. The magnitude of GHRH-induced GH release was greater in clones than in controls, whereas there was a greater inhibition of GHRH-induced GH release by SRIF in controls than in these clones. Lovendahl et al. [46] reported that genetic differences in cattle may be identified by GHRH stimulation of GH. Kazmer et al. [34] and Zinn et al. [42] reported that GH concentrations are greater in genetically superior bulls after GHRH administration. It has also been reported that cows that produce more milk have increased concentrations of GH compared with low-milk-producing cows [47]. Taken together, these results indicate that these clones are more responsive to GHRH and less responsive to SRIF than controls. There is no true estimate of the genetic merit of these clones, but they are all from the same genetic pool and cloned from a cow with high milk production. Although we do not have direct evidence, we speculate that the differences in concentrations of GH over time in clones may indicate that these clones are potentially of a superior genetic merit relative to controls.

Serum concentrations of IGF-I increased over time in clones and controls as previously reported in cattle [29, 31] and pigs [28]. However, averaged across all time points, IGF-I concentrations were greater in controls than in clones. Conner et al. [43] reported that bulls with greater plasma concentrations of IGF-I at a young age (at weaning) had slower rates of gain at 140 days postweaning than did bulls of a similar age with lower plasma concentrations of IGF-I at weaning. However, calves with lower plasma concentrations of IGF-I may have greater muscle and bone growth [43]. Therefore, lower concentrations of IGF-I in these clones may provide further evidence of the genetic superiority of these clones that may be expressed at an older age. Importantly, in terms of developmental change over time, patterns of IGF-I in serum were parallel between clones and controls.

IGFBPs are responsible for transporting IGF in the blood and extending the half-life of IGF-I when bound to IGF-I and an ALS, forming a ternary complex (150 kDa [37]). Therefore, it is expected that when concentrations of IGF-I are increased, there will be a concomitant increase in serum concentrations of IGFBP-3 [28, 48]. In the current study, the concentration of IGFBP-3 was significantly greater in controls than in clones, which paralleled the increased concentrations of IGF-I. There was no change over time in IGFBP-3 concentrations in clones and controls. In contrast, previous reports in newborn calves [29], newborn pigs [28], and growing beef calves [32] indicate that serum IGFBP-3 concentrations increase with age. The difference between this study and those of others in concentrations of IGFBP-3 could be due to the small number of animals in this study. Average concentrations of IGFBP-2 were not different between clones and controls, and IGFBP-2 concentrations did not change over time. Similarly, Harrell et al. [28] reported that IGFBP-2 was not affected by age in growing pigs. In contrast, Skaar et al. [29] reported a decrease in IGFBP-2 concentrations in calves between 12 and 45 wk of age. Overall, clones and controls were developmentally similar over time, with no change in IGFBP-3 and IGFBP-2 concentrations noted for either group.

Summary

The developmental patterns of somatic clones, in terms of the somatotropic axis, are similar to those of age-matched animals produced by AI reproduction. The variations in concentrations of GH, IGF-I, and IGFBP-3 may be a result of a difference in genetic merit, since these clones were produced from somatic cells from a single animal of high milk production and potentially superior genetic merit. The interesting finding that these clones respond differently to GHRH and SRIF may indicate that multiple clones from different genetic backgrounds are good research models for studying the effects of hormone and drug treatments by eliminating the variation of genetic influence. However, further studies are required using clones derived from different donor animals to validate this conclusion.


   FOOTNOTES
 
First decision: 13 August 2001.

1 This work was supported, in part, by the University of Connecticut Research Foundation. Back

2 Correspondence: Steven A. Zinn, Department of Animal Science, Room 102 George White, 3636 Horsebarn Rd. Ext., University of Connecticut, Storrs, CT 06269. FAX: 860 486 4375; szinn{at}canr.uconn.edu Back

Accepted: November 27, 2001.

Received: July 10, 2001.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KHS. Viable offspring derived from fetal and adult mammalian cells. Nature 1997; 385:810-813[CrossRef][Medline]
  2. Wakayama T, Perry AC, Zuccotti M, Johnson KR, Yanagimachi R. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 1998; 394:369-374[CrossRef][Medline]
  3. Wakayama T, Yanagimachi R. Cloning of male mice from adult tail-tip cells. Nat Genet 1999; 22:127-128[CrossRef][Medline]
  4. Wakayama T, Tateno H, Mombaerts P, Yanagimachi R. Nuclear transfer into mouse zygotes. Nat Genet 2000; 24:108-109[CrossRef][Medline]
  5. Rideout III WM, Wakayama T, Wutz A, Eggan K, Jackson-Grusby L, Dausman J, Yanagimachi R, Jaenisch R. Generation of mice from wild-type and targeted ES cells by nuclear cloning. Nat Genet 2000; 24:109-110[CrossRef][Medline]
  6. Kato Y, Tani T, Sotomaru Y, Kurokawa K, Kato J, Doguchi H, Yasue H, Tsunoda Y. Eight calves cloned from somatic cells of a single adult. Science 1998; 282:2095-2098[Abstract/Free Full Text]
  7. Wells DN, Misica PM, Tervit HR. Production of cloned calves following nuclear transfer with cultured adult mural granulosa cells. Biol Reprod 1999; 60:996-1005[Abstract/Free Full Text]
  8. Galli C, Duchi R, Moor RM, Lazzari G. Mammalian leukocytes contain all the genetic information necessary for the development of a new individual. Cloning 1999; 1:161-170
  9. Zakhartchenko V, Alberio R, Stojkovic M, Prelle K, Schernthaner W, Stojkovic P, Wenigerkind H, Wanke R, Duchler M, Steinborn R, Mueller M, Brem G, Wolf E. Adult cloning in cattle: potential of nuclei from a permanent cell line and from primary cultures. Mol Reprod Dev 1999; 54:264-272[CrossRef][Medline]
  10. Hill JR, Winger QA, Long CR, Looney CR, Thompson JA, Westhusin M. Development rates of male bovine nuclear transfer embryos adult and fetal cells. Biol Reprod 2000; 62:1135-1140[Abstract/Free Full Text]
  11. Kubota C, Yamakuchi H, Todoroki J, Mizoshita K, Tabara N, Barber M, Yang X. Six cloned calves produced from adult fibroblast cells after long-term culture. Proc Natl Acad Sci U S A 2000; 97:990-995[Abstract/Free Full Text]
  12. Tian XC, Xu J, Yang X. Normal telomere lengths found in cloned cattle. Nat Genet 2000; 26:272-273[CrossRef][Medline]
  13. Polejaeva IA, Chen SH, Vaught TD, Page RL, Mullins J, Ball S, Dai YF, Boone J, Walker S, Ayares DL, Colman A, Campbell KHS. Cloned pigs produced by nuclear transfer from adult somatic cells. Nature 2000; 407:86-90[CrossRef][Medline]
  14. Baguisi A, Behboodi E, Melican DT, Pollock JS, Destrempes MM, Cammuso C, Williams JL, Nims SD, Porter CA, Midura P, Palacios MJ, Ayres SL, Denniston RS, Hayes ML, Ziomek CA, Meede HM, Godke RA, Gavin WG, Overstrom EW, Echelard Y. Production of goats by somatic cell nuclear transfer. Nat Biotechnol 1999; 17:456-461[CrossRef][Medline]
  15. Lanza RP, Cibelli JB, Diaz F, Moraes CT, Farin PW, Farin CE, Hammer CJ, West MD, Damiani P. Cloning of an endangered species (Bos gaurus) using interspecies nuclear transfer. Cloning 2000; 2:79-91
  16. Hill JR, Roussel AJ, Cibelli JB, Edwards JF, Hooper RN, Miller MW, Thompson JA, Looney CR, Westhusin ME, Robl JM, Stice SL. Clinical and pathologic features of cloned transgenic calves and fetuses (13 case studies). Theriogenology 1999; 51:1451-1465[CrossRef][Medline]
  17. Taneja M, French R, Levine H, Tauro-Miller D, Yang X. Clinical and pathological status of cloned calves born pre-term. Theriogenology 2001; 55:293 (abstract)
  18. Renard JP, Chastant S, Chesne P, Richard C, Marchal J, Cordonnier N, Chavatte P, Vignon X. Lymphoid hypoplasia and somatic cloning. Lancet 1999; 353:1489-1491[CrossRef][Medline]
  19. Shiels P, Kind AJ, Campbell KHS, Waddington D, Wilmut I, Colman A, Schnieke AE. Analysis of telomere lengths in cloned sheep. Nature 1999; 399:316-317[Medline]
  20. Lanza RP, Cibelli JB, Blackwell C, Cristofalo VJ, Francis MK, Baerlocher GB, Mak J, Schertzer M, Chavez EA, Sawyer N, Lansdorp PM, West MD. Extension of cell life-span and telomere length in animals cloned from senescent somatic cells. Science 2000; 288:665-669[Abstract/Free Full Text]
  21. Wilmut I, Clark J, Harley CB. Laying hold on eternal life?. Nat Biotechnol 2000; 18:599-600[CrossRef][Medline]
  22. Lawrence TLJ, Fowler VR. Hormonal, genetic and immunological influences of growth. In: Growth of Farm Animals. Wallingford Oxon, U.K.: CAB International; 1997: 104–110
  23. Beerman DH, DeVol DL. Effects of somatotropin, somatotropin releasing factor and somatostatin on growth. Growth Regul Farm Anim 1991; 7:373-426
  24. Kazmer GW, Zinn SA, Strausbaugh LD. Short communication: growth hormone response to somatostatin-28 and growth hormone-releasing factor in dairy heifers. J Dairy Sci 2000; 83:2282-2284[Abstract]
  25. Carter-Su C, Schwartz J, Smit LS. Molecular mechanism of growth hormone action. Annu Rev Physiol 1996; 58:187-207[CrossRef][Medline]
  26. Jones JI, Clemons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 1995; 16:3-34[CrossRef][Medline]
  27. Cohick WS, McGuire MA, Clemmons DR, Bauman DE. Regulations of insulin-like growth factor binding proteins in serum and lymph of lactating cows by somatotropin. Endocrinology 1992; 130:1508-1514[Abstract]
  28. Harrell RJ, Thomas MJ, Boyd RD, Czerwinski SM, Steele NC, Bauman DE. Ontogenic maturation of the somatotropin/insulin-like growth factor axis. J Anim Sci 1999; 77:2934-2941[Abstract/Free Full Text]
  29. Skaar TC, Baumrucker CR, Deaver DR, Blum JW. Diet effects and ontogeny of alterations of circulating insulin-like growth factor binding proteins in newborn dairy calves. J Anim Sci 1994; 72:421-427[Abstract]
  30. Gerrard DE, Okamura CS, Grant AL. Expression and location of IGF binding proteins-2, -4, and -5 in developing fetal tissues. J Anim Sci 1999; 77:1431-1441[Abstract/Free Full Text]
  31. Schwarz FJ, Ropke R, Schams D, Kirchgessner M. 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 1992; 68:263-271
  32. Govoni KE, Hoagland TA, Zinn SA. Age related changes of somatotropin, insulin-like growth factor-I and insulin-like growth factor binding protein-2 and -3 in male and female Hereford calves. J Anim Sci 2000; 78:(suppl 1):129 (abstract)
  33. Enright BP, Taneja M, Schreiber D, Riesen J, Tian XC, Yang X. Puberty and early follicular dynamics in adult somatic cell derived cloned heifers. Theriogenology 2001; 55:267 (abstract)
  34. Kazmer GW, Zinn SA, Rycroft H, Campbell RM. Serum growth hormone in and semen characteristics of proven AI dairy sires after administration of growth hormone-releasing factor. Can J Anim Sci 1992; 72:959-963
  35. Le Roith D, Bondy C, Yakar S, Liu J, Butler A. The somatomedin hypothesis: 2001. Endocr Rev 2001; 22:53-74[Abstract/Free Full Text]
  36. Rajaram S, Baylink DJ, Mohan S. Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocr Rev 1997; 18:801-831[Abstract/Free Full Text]
  37. Vestergaard M, Purup S, Henkel P, Tonner E, Flint DJ, Jensen LR, Sejrsen K. Effects of growth hormone and ovariectomy on performance, serum hormones, insulin-like growth factor-binding proteins, and muscle fiber properties of prepubertal Friesen heifers. J Anim Sci 1995; 73:3574-3584[Abstract]
  38. Elsasser TH, Rumsey TS, Hammond AC. Influence of diet on basal and growth hormone-stimulated plasma concentrations of insulin-like growth factor-I in beef cattle. J Anim Sci 1989; 67:128-141
  39. Dahl GE, Elsasser TH, Capuco AV, Erdman RA, Peters RR. Effects of a long daily photoperiod on milk yield and circulating concentrations of insulin-like growth factor-I. J Dairy Sci 1997; 80:2784-2789[Abstract]
  40. Freake HC, Govoni KE, Guda K, Huang C, Zinn SA. Actions and interactions of thyroid hormone and zinc deficiency in the regulation of growth in rats. J Nutr 2001; 131:1135-1141[Abstract/Free Full Text]
  41. SAS. The SAS System Version 8. Cary, NC: Statistical Analysis System Institute Inc.; 1999
  42. Zinn SA, Kazmer GW, Rycroft H, Campbell RM. Growth hormone response after administration of growth hormone-releasing factor to proven dairy sires. Livest Prod Sci 1994; 40:157-164[CrossRef]
  43. Conner EE, Barao SM, Kimrey AS, Parlier AB, Douglass LW, Dahl GE. 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 2000; 78:2913-2918[Abstract/Free Full Text]
  44. Zinn SA, Purchas RW, Chapin LT, Peticlerc D, Merkel RA, Bergen WG, Tucker HA. Effects of photoperiod on growth, carcass composition, prolactin, growth hormone and cortisol in prepubertal and post-pubertal Holstein heifers. J Anim Sci 1986; 63:1804-1815
  45. Tripp MW, Hoagland TA, Dahl GE, Kimrey AS, Zinn SA. Methionine and somatotropin supplementation in growing beef cattle. J Anim Sci 1998; 76:1197-1203[Abstract/Free Full Text]
  46. Lovendahl P, Liboriussen T, Jensen J, Vestergaard M, Sejrsen K. Physiological predictors in calves of dairy breeds: part 1. Genetic parameters of basal and induced growth hormone secretion. Acta Agric Scand 1994; 44:169-176
  47. Hart IC, Bines JA, Balch CC, Cowie AT. Hormone and metabolite differences between lactating beef and dairy cattle. Life Sci 1975; 16:1285-1292[CrossRef][Medline]
  48. Skaar TC, Vega JR, Pyke SN, Baumrucker CR. Changes in insulin-like growth factor-binding proteins in bovine mammary secretions associated with pregnancy and parturition. J Endocrinol 1991; 131:127-133[Abstract]



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