Departments of Biomedical Sciences and of Physiology, and the Dalton Cardiovascular Institute, University of Missouri, Columbia, Missouri 65211
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The purpose of the current study was to examine IGFBP-3, -4, and -5 mRNA and protein expression levels as a function of muscle type, age, and regrowth from an immobilization-induced atrophy in Fischer 344 × Brown Norway rats. IGFBP-3 mRNA expression in the 4-mo-old animals was significantly higher in the red and white portions of the gastrocnemius muscle compared with the soleus muscle. However, there were no significant differences in IGFBP-3 mRNA expression among any of the muscle groups in the 30-mo-old animals. There were no significant differences in IGFBP-5 mRNA expression in any of the muscle groups, whereas in the 30-mo-old animals there was significantly less IGFBP-5 mRNA expression in the white gastrocnemius compared with the red gastrocnemius muscles. Although IGFBP-3 and -5 proteins were detected in the type I soleus muscle with Western blot analyses, no detection was observed in the type II red and white portions of the gastrocnemius muscle. Aging from adult (18 mo) to old animals (30 mo) was associated with decreases in IGFBP-3 mRNA and protein and IGFBP-5 protein only in the soleus muscle. After 10 days of recovery from 10 days of hindlimb immobilization, IGFBP-3 mRNA and protein increased in soleus muscles from young (4-mo) rats; however, only IGFBP-3 protein increased in the old (30-mo) rats. Whereas there were no changes in IGFBP-5 mRNA expression during recovery, IGFBP-5 protein in the 10-day-recovery soleus muscle did increase in the young, but not in the old, rats. Because one of the functions of IGFBPs is to modulate IGF-I action on muscle size and phenotype, it is hypothesized that IGFBP-3 and -5 proteins may have potential modulatory roles in type I fiber-dominated muscles, aging, and regrowth from atrophy.
insulin-like growth factor-binding protein; insulin-like growth factor I; growth; hypertrophy; fiber type
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
SKELETAL MUSCLE IS A PLASTIC TISSUE that retains an intrinsic ability to alter its structural and functional properties to a given environment (12). For example, skeletal muscle atrophies under conditions of immobilization or unweighting (11, 34); however, when muscle in young animals (2-6 mo) is reloaded, the muscle retains the ability to recover its previously lost mass (10). Recently, we (14) and others (9) have found that muscle in aged animals does not retain the ability to recover lost muscle mass from immobilization (14) or hypertrophy during functional overload (9). The inability for skeletal muscle in aged animals to regrow or hypertrophy suggests that either positive stimulators of muscle growth are "missing" or negative regulators of muscle hypertrophy are highly active. Currently, there is little evidence examining what different possible factors could contribute to the inability of the aged skeletal muscle to adapt to increases in skeletal muscle load.
When skeletal muscle is challenged with an increased mechanical load, there are rapid increases in autocrine/paracrine growth factors that activate signaling mechanisms that promote skeletal muscle hypertrophy (3, 29). One such growth factor system is insulin-like growth factor I (IGF-I), which plays an essential role in the formation and maintenance of skeletal muscle (19). Mice lacking the IGF-I receptor exhibit marked muscle hypoplasia and die soon after birth because of respiratory failure (24), and mice with a dominant negative IGF-I receptor have smaller skeletal muscles (19). In contrast, mice overexpressing IGF-I exhibit skeletal muscle hypertrophy (16, 27). In addition, rats infused with exogenous IGF-I specifically on the skeletal muscle exhibit muscle hypertrophy (4), and the exogenous IGF-I also rescues skeletal muscle from sarcopenia (14).
Endogenous IGF-I likely participates in the regulation of numerous myogenic components during overload-induced hypertrophy in mature mammalian skeletal muscle (17). Overloading of skeletal muscle produces hypertrophy and is associated with increases in IGF-I mRNA and peptide level (1). In addition, increased IGF-I expression within skeletal muscle fibers after resistance exercise has been found with immunohistochemical procedures in rats (35) and humans (32). On the other hand, unloading of skeletal muscle is associated with a lowering of IGF-I mRNA (6). Furthermore, skeletal muscle IGF-I mRNA expression was decreased only during maturation, but not with aging (21). Therefore, on the basis of this evidence, it is likely that IGF-I has a significant role in the skeletal muscle growth process.
IGF-binding proteins (IGFBPs) are multifunctional proteins that transport IGFs in circulation, localize IGFs in specific cell types, and alter binding characteristics of IGFs to receptors (23). Six different IGFBP proteins have been cloned and sequenced (33). Initially, IGFBPs were thought to function as proteins that extended the half-life of IGFs in the circulation and also inhibited the binding of IGF to a specific receptor (33). The prevention of IGF-I from binding a receptor was thought to be essential, since IGF-I can interact with the insulin receptor, and IGF-I concentrations in the serum are 1,000 times higher than those of insulin (30). Now it is known that IGFBPs can localize in the extracellular matrix, modulate IGFs' interaction with a receptor, and/or act as a localized storage depot for IGFs (33). Thus IGFBPs likely modulate IGF-I's effectiveness and exert IGF-I-independent effects on various tissues. Although the interactions of IGFBPs and IGF-I have been investigated very carefully, very little information is known about the changes in IGFBP protein expression in skeletal muscle during changes in loading patterns of the animals. Currently, there is less information available on whether IGFBP protein expression might be altered in old animals with age-induced muscle atrophy. Therefore, the purposes of the current report were to determine protein levels of IGFBP-3, -4, and -5 in slow and fast muscles and their response to increased loading of these muscles in young and old rats. The hypotheses of this study were that IGFBP-3, -4, and -5 protein concentrations would be the same in type I and II muscles, would be altered with aging, and would fail to respond during reloading of old muscles recovering from atrophy.
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Materials. IGFBP-3, IGFBP-4, and IGFBP-5 antibodies were purchased from GroPep (Adelaide, BC, Australia). All remaining chemicals were purchased from Sigma Chemical (St. Louis, MO) or Fisher Scientific.
Animals. All animals were maintained in animal care facilities, kept on a 12:12-h light-dark cycle, and given rat chow and water ad libitum. Young (4-mo), adult (18-mo), and old (30-mo) male F1-generation Fischer 344 × Brown Norway rats were obtained from NIA (Harlan, Indianapolis, IN).
Hindlimb immobilization. The hindlimb immobilization of the rats was performed according to the previously described procedures of Booth (10). Rats were lightly anesthetized with an intraperitoneal injection of ketamine (50 mg/kg body wt) and acepromazine (5 mg/kg body wt) for attachment of the casting material. The hindlimbs of the animals were fixed in plantar flexion so that calf muscle was in a shortened position, as described previously (10). The animals were then checked daily for damage to casting material, which was subsequently repaired as necessary. After 10 days, the casting material was removed from anesthetized rats, and the animals were returned to their cages. The animals were allowed to recover for 10 days and then were killed. The muscles were removed and processed (see Muscle collection and preparation). There were multiple reasons for the use of this model. By utilizing a model of hindlimb immobilization, significant amounts of atrophy can be produced in both type I- and II-predominant muscles (~30-40% decrease in muscle wet weight and muscle protein content), and with the subsequent removal of the casting material, a reloaded muscle is induced to regrow through normal ambulation of the animal (10). In addition, after 30 days of recovery, whereas muscle in young animals regrows from limb immobilization (10), muscle in old animals does not regrow (14). Finally, we believe that this model mimics the response that would be exhibited by a human who is forced into extended periods of bed rest and then required to assume normal ambulation.
Muscle collection and preparation.
At the specified time points, the animals were anesthetized (75 mg/kg
ketamine, 3 mg/kg xylazine, and 5 mg/kg acepromazine), and the muscle
was removed from the animals, weighed, then immediately frozen in
liquid nitrogen, and finally stored at 80°C until further analysis.
The muscle was later homogenized as 5% (wt/vol) in buffer containing
50 mM HEPES (pH 7.4), 0.1% Triton X-100, 4 mM EGTA, 10 mM EDTA, 15 Na4P2O7 · 10 H2O, 100 mM
-glycerophosphate, 25 mM NaF, 5 mM
NaVO4, 50 µg/ml leupeptin, 50 µg/ml pepstatin, and 33 µg/ml aprotinin. All homogenizations were performed on ice with a
ground glass homogenizer by use of a variable speed motor. The
homogenate was then centrifuged at 13,000 rpm for 10 min. Protein
concentrations were determined on all samples through the Bradford
protein assay (Bio-Rad, Hercules, CA).
Western blotting. Equal amounts of total protein were then resolved on SDS-PAGE gels and subsequently transferred to nitrocellulose membranes, as previously described (13). All blots were then incubated with Ponceau S (Sigma Chemical) to ensure equal loading (data not shown). The membranes were then blocked with 5% bovine serum albumin (BSA) in Tris-buffered saline with 0.1% Tween (TBS-T) and 1 mM sodium orthovanadate. All membranes were then probed overnight with the appropriate antibody, which was diluted in 5% BSA-TBS. The antibodies were used at the following concentrations: IGFBP-3 (1:2,000), IGFBP-4 (dilution ranges attempted were 1:4,000-1:10,000), and IGFBP-5 (1:5,000). The membranes were washed in TBS-T and then incubated for 1 h with horseradish peroxidase (HRP)-conjugated rabbit, goat, or mouse secondary antibody (1:5,000 rabbit, 1:8,000 mouse; Amersham Pharmacia Biotech, Piscataway, NJ) (1:8,000 goat, Jackson Laboratories). Finally, the HRP activity was detected using enhanced chemiluminescence reagent (NEN Life Science Products, Boston, MA). The membrane was exposed to autoradiographic film (Kodak-XAR5), with the exposure time adjusted to keep the integrated optical densities within a linear and nonsaturated range. The bands were then scanned utilizing a densitometer (Molecular Dynamics) and quantified using ImageQuant software (Molecular Dynamics).
RNA extraction.
Total RNA was extracted from preweighed frozen muscle samples using
TRIzol reagent (Invitrogen Technologies, San Diego, CA) on the basis of
previously described techniques (15). RNA concentrations were determined by measuring the optical density at 260 nm. The quality
of the RNA was examined visually by ethidium bromide staining of 18S
and 28S under ultraviolet light. The samples were subsequently stored
at 80°C for subsequent analysis.
RT. Two micrograms of total RNA were reverse transcribed for each sample with the SuperScript II RT (Invitrogen) mixed oligo(dT) (Invitrogen) and random decamers (500 µg/ml; Ambion, Austin, TX) in a 20-µl reaction volume at 42°C for 50 min. The reaction was inactivated by incubation at 70°C for 15 min. The samples were subsequently stored at 4°C for later analyses.
PCR.
All methods were adapted according to the previously described methods
(2). A semiquantitative RT-PCR was employed using 18S as
an internal standard (Classic II 18S Ambion) in each reaction. Primers
utilized for IGFBP-3, -4, and -5 have been previously described
(2, 26). The primer sequences utilized (which read in a 5'
3' direction) were as follows: IGFBP-3 sense:
5'-CAGCAACCTGAGTGCCTACC-3', IGFBP-3 antisense:
5'-CTGTCTCCCGCTTAGACTCG-3' (product size 263 bp, GenBank M31837),
IGFBP-4 sense: 5'-CCTGGGCTTGGGGATGC-3', IGFBP-4 antisense:
5'-AGGGGTTGAAGCTGTTGTTGG-3' (product size 212 bp, GenBank X76066),
IGFBP-5 sense: 5'-CACGCCTTCGACAGCAGTAAC-3', and IGFBP-5 antisense:
5'-GTCGGGAATGGGGAGTGTCT-3' (product size 214 bp, GenBank NM_012817).
All primers were purchased from Invitrogen Technologies.
Statistics. All data were expressed as means ± SE. Statistical significance was determined using a one-way analysis of variance for multiple comparisons followed by a Tukey's post hoc test. A P value of <0.05 was considered significant.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Body and muscle masses of 4-mo-, 18-mo-, and 30-mo-old animals.
There was a significant 40 and 48% increase in the body mass of the
18- and 30-mo-old animals compared with the 4-mo-old animals, respectively, in the aging study (Table
1). However, there was no significant
difference in body mass between the 18- and 30-mo-old animals. In
addition, there were no differences in absolute soleus muscle mass
between any of the age groups, but there were significant reductions in
the absolute gastrocnemius mass in the 30-mo-old animals by 17%
compared with the 4- and 18-mo-old animals. However, the normalized
soleus and gastrocnemius muscle masses were significantly less by 20 and 28% and by 28 and 44% in 18- and 30-mo-old animals compared with
the 4-mo-old animals, respectively (Table 1). Only the normalized
gastrocnemius muscle mass was significantly different between the 18- and 30-mo-old animals.
|
Muscles composed of distinct fiber types express varying levels of
IGFBP-3, IGFBP-4, and IGFBP-5 mRNA and protein in 4-, 18-, and
30-mo-old animals.
IGFBP-3 mRNA expression was significantly higher by ~50% in
the red and white gastrocnemius muscle compared with the soleus muscle
in the 4-mo-old animals (Fig.
1A); however, there were no
significant differences in IGFBP-3 mRNA expression between any of
the different muscle types in the 30-mo-old animals (Fig. 1D).
|
|
Age levels of IGFBP-3 and IGFBP-5 mRNA and protein in the soleus
muscle.
IGFBP-3 mRNA expression was significantly higher in the soleus muscles
from the 18-mo-old animals by 90 and 104% compared with the 4- and
30-mo-old animals, respectively. However, there was no difference in
IGFBP-3 mRNA expression in the soleus muscle between the 4- and
30-mo-old animals (Fig. 3A).
|
|
Ten-day recovery levels of IGFBP-3 and IGFBP-5 mRNA and protein in
the soleus muscle after a 10-day bout of hindlimb immobilization in 4- and 30-mo-old animals.
IGFBP-3 mRNA significantly increased after 10 days of recovery from a
10-day bout of immobilization by 49% in the soleus isolated from
4-mo-old animals (Fig. 5A).
However, there was no change (P = 0.16) detected in
IGFBP-3 mRNA expression in the soleus muscle after 10 days of recovery
in the 30-mo-old animals (Fig. 5C).
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Although IGFBP-3 and -5 proteins were found in the type I muscle
fiber-dominated (soleus) muscle, their absence, at least at the
sensitivity of Western analysis, in type IIb (white gastrocnemius) muscle fiber-dominated muscles was unexpected, because two studies have
reported the existence of mRNAs for IGFBP-3 and -5 in type II muscles
(5, 7), and their mRNA presence in type II muscles was
verified in the current study (Figs. 1 and 2). The rat soleus muscle is
composed of 86% type I muscle fibers, whereas the red and white
portions of the gastrocnemius muscles of 5-mo-old rats had ~20% type
I myosin heavy-chain expression (20) and no type I muscle
fibers, respectively (18). Thus a novel suggestion of the
aforementioned observations may be that important translational and
posttranslational mechanisms exist for the regulation of IGFBP-3, -4, and -5 expression in type II fiber-dominated rat muscle (Table 2).
|
Previous work on the expression of IGFBP proteins in skeletal muscle fiber types had been restricted to tissue culture. Conditioned media containing rabbit adult myoblasts obtained from type I muscle exhibited the presence of a 30- to 31-kDa band with ligand blotting that was interpreted by Barjot et al. (7) to correspond to IGFBP-5. However, IGFBP-5 protein was not detected in the conditioned media from adult myoblasts isolated from a rabbit muscle consisting of nearly 100% type II fibers (7). The current observed association (Fig. 3) for a differential expression of IGFBP-5 proteins between types I and IIb muscles extends the aforementioned developmental relationship and allows formulation of a hypothesis that IGFBP-5 either has a causal effect on fiber type phenotype or is a secondary consequence of muscle phenotype. The role of IGFBP-5 in the modulation of the IGF system between types I and II muscles in mature and aged animals remains to be defined.
Barjot et al. (7) found no differences in the amount of IGFBP-3 protein secreted into the media between types I and II myoblasts. In contrast, whereas IGFBP-3 protein was found in the type I soleus muscle, it was undetectable with Western analysis in whole muscle homogenates of the red and white gastrocnemius (Fig. 1). Because previous reports and current data detected IGFBP-3 mRNA in type II muscles (8), IGFBP-3 protein expression may be regulated at the translational and/or posttranslational level in muscles made up of mainly type II fibers.
Because multiple publications report that excess IGF preferentially increases the proportion of type II fibers while decreasing that of type I fiber, support then exists for a hypothesis that the IGF-I system could play a role in fiber type determination in adult skeletal muscles. Lynch et al. (25) reported that IGF-I treatment increased the proportion of type IIa and type IIb fibers and decreased the proportion of type I fibers in the extensor digitorum longus (EDL) muscles of dystrophic mice. Hennessey et al. (22) found that administration of recombinant growth hormone for 6 mo induced significant increases in IGF-I expression, which were associated with significant increases in muscle strength and in the proportion of type II fibers. Specific overexpression of IGF-I in striated muscles of transgenic mice was associated with a shift toward more oxidative fiber types [likely types IIa and IIx (16)]. In addition, this finding was extended to a second IGF-I transgenic mouse line that specifically overexpressed IGF-I in skeletal muscle, by report of an increase in type IIb fibers and a decrease in type IIa fibers in the EDL muscle compared with wild-type mice (27). Therefore, because several studies have reported fiber type shifts due to excess IGF-I, it is possible to suggest that high levels of IGFBP-3 and -5 protein expression in slow fibers could attenuate and/or prevent IGF-I from modulating the fiber type expression in the soleus muscle. However, this suggestion remains to be tested.
Previous publications have indicated that IGFBP mRNA transcript concentrations differ among muscle types (6, 8). For example, IGFBP-5 mRNA levels are lower in the soleus muscle (predominantly type I fibers) compared with the gastrocnemius and tibalis anterior muscles (predominantly type II fibers) of 200-g male Wistar rats (8). However, in the current study, IGFBP-5 mRNA showed no difference in muscle type specificity in the young animals, whereas the IGFBP-5 protein shows the opposite fiber type predominance by being higher in the soleus muscle of 4-mo-old rats (Fig. 2; Table 2). In addition, the current study found that IGFBP-3 mRNA expression is higher in the red and white portions of the gastrocnemius muscles compared with the soleus muscle of 4-mo-old rats. This again differs from the findings of Bayol et al. (8), who found no differences in IGFBP-3 mRNA expression between muscle types, and who did not report IGFBP protein levels. The difference in the above mRNA findings could be partially explained by the different strain, as well as the different age, of the rats. More specifically, our 4-mo-old rats were F1-generation Fischer 344 × Brown Norway, whereas Bayol et al. utilized ~2-mo-old Wistar rats. Thus our data suggest that IGFBP-3, -4, and -5 protein expression appears to be regulated at the posttranscriptional level in the red and white portions of the gastrocnemius muscle.
Also, previous publications have indicated that IGFBP mRNA expression differs depending on the load of the muscle (6). IGFBP-5 mRNA decreased at the 2nd and 8th days of compensatory overload of the soleus muscle in 2-mo-old mice (6); yet on the 10th day of regrowth from atrophy in the current study, IGFBP-5 mRNA did not change, whereas IGFBP-5 protein increased in the soleus muscles of 4-mo-old rats (Fig. 6; Table 2). This suggests that a posttranscriptional mechanism may be regulating the increase in IGFBP-5 protein expression in the soleus muscle with increased load. Intriguingly, the hypothesized posttranscriptional mechanism might be dysfunctional in the 30-mo-old rats, in that there was no increase in IGFBP-5 protein expression with increased load.
Owino et al. (28) concluded that the downregulation of the IGF-I system, particularly the attenuated increase in the autocrine skeletal muscle isoform of IGF-I mRNA (designated as "mechano growth factor" mRNA) levels, as well as IGF-I receptor mRNA levels in response to overload, is likely to have an important role in the impaired growth potential of old skeletal muscle. The current observation that IGFBP-5 protein increased in the soleus muscle only of 4-mo-old, but not of 30-mo-old, rats during muscle regrowth (Fig. 6) extends the observations of Owino et al. (28) to the protein level and to another component of the IGF-I system. However, not all components of the IGF-I system are altered with aging, as similar significant increases in IGF-IEa mRNA (28) and in IGFBP-3 protein (Fig. 5) occurred in the young and old overloaded and atrophied-regrowing muscles, respectively.
Some of the changes in IGFBP mRNAs and proteins are not in parallel with aging. At the mRNA and protein levels, IGFBP-3 protein expression in the soleus muscle was not different between the 4- and 30-mo-old rats (Fig. 3), confirming previous gastrocnemius data (31). However, IGFBP-3 mRNA and protein and normalized muscle mass were significantly elevated in the soleus muscle of 18-mo-old animals compared with 4-mo-old rats in the current study. Although absolute and normalized soleus muscle mass did not change from 18 to 30 mo of age, soleus muscles in similarly aged rats of the same strain are atrophied in another report (5), so it is noteworthy that both IGFBP-3 and -5 proteins are decreased before the expected mass loss in the 30-mo-old soleus muscles in the current study. IGFBP-5 mRNA expression remained elevated at 18 and 30 mo of age in the soleus muscle (Fig. 4), extending similar results for the gastrocnemius muscle (21). Again, results of the present study, combined with other data (21), suggest that regulation at the level of protein translation or posttranslation could determine the expression levels of IGFBP-5 protein in skeletal muscle during aging.
The results of the current study demonstrate that IGFBP-3 and -5 protein expression in skeletal muscles differs between types I and II fiber-dominated muscles, mature and aging animals, and young and old rats during regrowth from limb immobilization. Through the examination of our data and data published by other groups, it appears that IGFBP-3 and IGFBP-5 protein expression in skeletal muscle could be regulated at the level of protein translation/posttranslation, whereas soleus muscle IGFBP-3 expression could be partially regulated at the transcriptional level. Clearly, additional experiments are necessary to determine how IGFBP-3 and -5 modulate IGF-I function in skeletal muscle.
![]() |
ACKNOWLEDGEMENTS |
---|
We thank Dr. Barry Prior, Jane Chen, and Andrew Wheeler for helpful technical advice.
![]() |
FOOTNOTES |
---|
This work was supported by National Institutes of Health (NIH) Grants NIA-18881 and AR-19393. E. E. Spangenburg was funded by NIH Grant AR-48514.
Address for reprint requests and other correspondence: F. W. Booth, Univ. of Missouri, Dept. of Veterinary Biomedical Sciences, E102 Vet. Med. Bldg., 1600 E. Rollins, Columbia, MO 65211 (E-mail: boothf{at}missouri.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
First published October 22, 2002;10.1152/ajpendo.00253.2002
Received 10 June 2002; accepted in final form 11 October 2002.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Adams, GR.
The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy.
J Appl Physiol
81:
2509-2516,
1996
2.
Adams, GR,
and
Haddad F.
Acute cellular and molecular responses to resistance exercise.
J Appl Physiol
93:
394-4-3,
2002
3.
Adams, GR,
Haddad F,
and
Baldwin KM.
Time course of changes in markers of myogenesis in overloaded rat skeletal muscles.
J Appl Physiol
87:
1705-1712,
1999
4.
Adams, GR,
and
McCue SA.
Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats.
J Appl Physiol
84:
1716-1722,
1998
5.
Alway, SE,
Degens H,
Lowe DA,
and
Krishnamurthy G.
Increased myogenic repressor Id mRNA and protein levels in hindlimb muscles of aged rats.
Am J Physiol Regul Integr Comp Physiol
282:
R411-R422,
2002
6.
Awede, B,
Thissen J,
Gailly P,
and
Lebacq J.
Regulation of IGF-I, IGFBP-4 and IGFBP-5 gene expression by loading in mouse skeletal muscle.
FEBS Lett
461:
263-267,
1999[ISI][Medline].
6a.
Awede, BL,
Thissen JP,
and
Lebacq J.
Role of IGF-I and IGFBPs in the changes of mass and phenotype induced in rat soleus muscle by clenbuterol.
Am J Physiol Endocrinol Metab
282:
E31-E37,
2002
7.
Barjot, C,
Navarro M,
Cotten ML,
Garandel V,
Bernardi H,
Bacou F,
and
Barenton B.
Rabbit slow and fast skeletal muscle-derived satellite myoblast phenotypes do not involve constitutive differences in the components of the insulin-like growth factor system.
J Cell Physiol
169:
227-234,
1996[ISI][Medline].
8.
Bayol, S,
Loughna PT,
and
Brownson C.
Phenotypic expression of IGF binding protein transcripts in muscle, in vitro and in vivo.
Biochem Biophys Res Commun
273:
282-286,
2000[ISI][Medline].
9.
Blough, ER,
and
Linderman JK.
Lack of skeletal muscle hypertrophy in very aged male Fischer 344 × Brown Norway rats.
J Appl Physiol
88:
1265-1270,
2000
10.
Booth, FW.
Regrowth of atrophied skeletal muscle in adult rats after ending immobilization.
J Appl Physiol
44:
225-230,
1978
11.
Booth, FW.
Effect of limb immobilization on skeletal muscle.
J Appl Physiol
52:
1113-1118,
1982
12.
Booth, FW,
and
Baldwin KM.
Muscle plasticity: energy demand and supply processes.
In: Handbook of Physiology. Exercise: Regulation and Integration of Multiple Systems. Bethesda, MD: Am. Physiol. Soc, 1996, sect. 12, chapt. 24, p. 1075-1123.
13.
Chakravarthy, MV,
Abraha TW,
Schwartz RJ,
Fiorotto ML,
and
Booth FW.
Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3'-kinase/Akt signaling pathway.
J Biol Chem
275:
35942-35952,
2000
14.
Chakravarthy, MV,
Davis BS,
and
Booth FW.
IGF-I restores satellite cell proliferative potential in immobilized old skeletal muscle.
J Appl Physiol
89:
1365-1379,
2000
15.
Chomczynski, P,
and
Sacchi N.
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
Anal Biochem
162:
156-159,
1987[ISI][Medline].
16.
Coleman, ME,
DeMayo F,
Yin KC,
Lee HM,
Geske R,
Montgomery C,
and
Schwartz RJ.
Myogenic vector expression of insulin-like growth factor I stimulates muscle cell differentiation and myofiber hypertrophy in transgenic mice.
J Biol Chem
270:
12109-12116,
1995
17.
Coolican, SA,
Samuel DS,
Ewton DZ,
McWade FJ,
and
Florini JR.
The mitogenic and myogenic actions of insulin-like growth factors utilize distinct signaling pathways.
J Biol Chem
272:
6653-6662,
1997
18.
Delp, MD,
and
Duan C.
Composition and size of type I, IIA, IID/X, and IIB fibers and citrate synthase activity of rat muscle.
J Appl Physiol
80:
261-270,
1996
19.
Fernandez, AM,
Dupont J,
Farrar RP,
Stannard B,
and
LeRoith D.
Muscle-specific inactivation of the IGF-I receptor induces compensatory hyperplasia in skeletal muscle.
J Clin Invest
109:
347-355,
2002
20.
Haddad, F,
Qin AX,
Zeng M,
McCue SA,
and
Baldwin KM.
Effects of isometric training on skeletal myosin heavy chain expression.
J Appl Physiol
84:
2036-2041,
1998
21.
Hamilton, MT,
Marsh DR,
Criswell DS,
Lou W,
and
Booth FW.
No effect of aging on skeletal muscle insulin-like growth factor mRNAs.
Am J Physiol Regul Integr Comp Physiol
269:
R1183-R1188,
1995
22.
Hennessey, JV,
Chromiak JA,
DellaVentura S,
Reinert SE,
Puhl J,
Kiel DP,
Rosen CJ,
Vandenburgh H,
and
MacLean DB.
Growth hormone administration and exercise effects on muscle fiber type and diameter in moderately frail older people.
J Am Geriatr Soc
49:
852-858,
2001[ISI][Medline].
23.
Hwa, V,
Oh Y,
and
Rosenfeld RG.
The insulin-like growth factor-binding protein (IGFBP) superfamily.
Endocr Rev
20:
761-787,
1999
23a.
Lewis, MI,
Horvitz GD,
Clemmons DR,
and
Fournier M.
Role of IGF-I and IGF-binding proteins within diaphragm muscle in modulating the effects of nandrolone.
Am J Physiol Endocrinol Metab
282:
E483-E490,
2002
24.
Liu, JP,
Baker J,
Perkins AS,
Robertson EJ,
and
Efstratiadis A.
Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r).
Cell
75:
59-72,
1993[ISI][Medline].
25.
Lynch, GS,
Cuffe SA,
Plant DR,
and
Gregorevic P.
IGF-I treatment improves the functional properties of fast- and slow-twitch skeletal muscles from dystrophic mice.
Neuromuscul Disord
11:
260-268,
2001[ISI][Medline].
26.
Mewar, R,
and
McMorris FA.
Expression of insulin-like growth factor-binding protein messenger RNAs in developing rat oligodendrocytes and astrocytes.
J Neurosci Res
50:
721-728,
1997[ISI][Medline].
27.
Musaro, A,
McCullagh K,
Paul A,
Houghton L,
Dobrowolny G,
Molinaro M,
Barton ER,
Sweeney HL,
and
Rosenthal N.
Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle.
Nat Genet
27:
195-200,
2001[ISI][Medline].
28.
Owino, V,
Yang SY,
and
Goldspink G.
Age-related loss of skeletal muscle function and the inability to express the autocrine form of insulin-like growth factor-1 (MGF) in response to mechanical overload.
FEBS Lett
505:
259-263,
2001[ISI][Medline].
29.
Sakuma, K,
Watanabe K,
Sano M,
Uramoto I,
and
Totsuka T.
Differential adaptation of growth and differentiation factor 8/myostatin, fibroblast growth factor 6 and leukemia inhibitory factor in overloaded, regenerating and denervated rat muscles.
Biochim Biophys Acta
1497:
77-88,
2000[ISI][Medline].
30.
Schneider, MR,
Wolf E,
Hoeflich A,
and
Lahm H.
IGF-binding protein-5: flexible player in the IGF system and effector on its own.
J Endocrinol
172:
423-440,
2002
31.
Severgnini, S,
Lowenthal DT,
Millard WJ,
Simmen FA,
Pollock BH,
and
Borst SE.
Altered IGF-I and IGFBPs in senescent male and female rats.
J Gerontol A Biol Sci Med Sci
54:
B111-B115,
1999[Abstract].
32.
Singh, MA,
Ding W,
Manfredi TJ,
Solares GS,
O'Neill EF,
Clements KM,
Ryan ND,
Kehayias JJ,
Fielding RA,
and
Evans WJ.
Insulin-like growth factor I in skeletal muscle after weight-lifting exercise in frail elders.
Am J Physiol Endocrinol Metab
277:
E135-E143,
1999
33.
Stewart, CE,
and
Rotwein P.
Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors.
Physiol Rev
76:
1005-1026,
1996
34.
Thomason, DB,
and
Booth FW.
Atrophy of the soleus muscle by hindlimb unweighting.
J Appl Physiol
68:
1-12,
1990
35.
Yan, Z,
Biggs RB,
and
Booth FW.
Insulin-like growth factor immunoreactivity increases in muscle after acute eccentric contractions.
J Appl Physiol
74:
410-414,
1993[Abstract].