| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Other Original Studies |
Insulin-Like Growth Factor I Axis in Prepubertal Girls1
Connecticut Children’s Medical Center (A.E., T.P.S.), University of Connecticut Health Center, Farmington, Connecticut 06030; Department of Pediatrics (R.N., D.M.C.), University of California, Irvine, College of Medicine, Irvine, California 92612; and Departments of Medicine, Biochemistry, and Physiology (S.M.), Loma Linda University, Pettis Veteran’s Administration Medical Center, Loma Linda, California 92354
Address all correspondence and requests for reprints to: Dan M. Cooper, M.D., Professor of Pediatrics, University of California, Irvine, College of Medicine, Clinical Research Center, Building 25, ZOT 4094-03, 101 The City Drive, Orange, California 92868. E-mail: dcooper{at}uci.edu
Abstract
We recently demonstrated that a brief endurance type training
program led to increases in thigh muscle mass and peak oxygen
uptake (
O2) in prepubertal girls. In this study, we
examined the effect of training on the GH
insulin-like growth factor
I (GHIGF-I) axis, a system known to be involved both in the process
of growth and development and in the response to exercise. Healthy
girls (mean age 9.17 ± 0.10 yr old) volunteered for the study and
were randomized to control (n = 20) and training groups (n =
19) for 5 weeks. Peak O2, thigh muscle volume, and
blood samples [for IGF-I, IGF-binding proteins (IGFBP)-1 to -6, and
GHBP] were measured. At baseline, IGF-I was significantly correlated
with both peak O2 (r = 0.44,
P < 0.02) and muscle volume (r = 0.58,
P < 0.004). IGFBP-1 was negatively correlated with
muscle volume (r = -0.71, P < 0.0001), as
was IGFBP-2. IGFBP-4 and -5 were significantly correlated with muscle
volume. We found a threshold value of body mass index percentile (by
age) of about 71, above which systematic changes in GHBP, IGFBP-1, and
peak O2 per kilogram were noted, suggesting
decreases in the following: 1) GH function, 2) insulin sensitivity, and
3) fitness. Following the training intervention, IGF-I increased in
control (19.4 ± 9.6%, P < 0.05) but not
trained subjects, and both IGFBP-3 and GHBP decreased in the
training group (-4.2 ± 3.1% and -9.9 ± 3.8%,
respectively, P < 0.05). Fitness in prepubertal
girls is associated with an activated GHIGF-I axis, but,
paradoxically, early in a training program, children first pass through
what appears to be a neuroendocrine state more consistent with
catabolism.
NORMAL GROWTH IN children is regulated in
large measure through the actions of the GHinsulin-like growth
factor I (GHIGF-I) axis, a system of growth hormones and mediators
that modulates growth in many tissues. A variety of environmental
factors, the most thoroughly studied to date being nutrition
(1), can influence elements of the GHIGF-I axis and,
ultimately, growth itself. Recent work from this and other laboratories
in human and animal models has shown that exercise and levels of
physical activity also influence the GHIGF-I axis and growth
(2, 3). The present study was designed to examine the role
of fitness and the effect of brief exercise training on the GHIGF-I
axis in prepubertal girls.
This is an important yet relatively understudied group. Although it is recognized that optimal levels of exercise during childhood may attenuate obesity (4) and prevent osteoporosis and cardiovascular disease in adulthood (5), epidemiologic and physiologic evidence suggests that American girls are now becoming less physically active in early puberty. The long-term consequences of reduced exercise and the underlying mechanisms responsible for beneficial effects of exercise in children are not well understood.
Controversy still surrounds the ability of exercise training to
measurably influence functional fitness, muscle mass, or
cardiorespiratory responses to exercise in children
(6, 7, 8, 9). Some investigators have reasoned that the
generally high levels of physical fitness found naturally in
prepubertal children would make it difficult to alter levels of
activity sufficiently to produce a measurable response. Moreover,
whether or not the GHIGF-I axis, which naturally is changing so
dynamically in children, could further be influenced by exercise is not
known.
In the present cohort of prepubertal girls, the effect of the
prospective exercise training program on peak oxygen uptake
(O2), body weight, height, and magnetic
resonance imaging-determined muscle mass and body adiposity has already
been published (10). In this previous study, we
demonstrated that a relatively brief training intervention (5 weeks)
led to small but significant increases in thigh muscle volume
(+4.3 ± 0.9%, P < 0.005) and peak
O2 (+9.5 ± 6%, P <
0.05) that were not observed in untrained control subjects. Moreover,
total energy expenditure, measured by the doubly labeled water
technique, was significantly greater (17%, P < 0.02)
in the training compared with control group subjects.
In previous studies of adults and children, levels of fitness are known
to be correlated with circulating levels of IGF-I. Thus, we
hypothesized that exercise training would stimulate the GHIGF-I axis
and be associated with increases in circulating levels of IGF-I.
In the present study, we first examined the interrelationships among
the mediators of the GHIGF-I axis, fitness, body weight, and thigh
muscle volume. We measured IGF-I, the major circulating IGF-binding
proteins (IGFBP)-1 to -6, and GH-binding protein (GHBP). GHBP is the
extracellular component of the GH receptor and is, in some
circumstances, related to the relative quantity of tissue GH receptors
(11). Because the study design included measurements of
thigh muscle volume by magnetic resonance imaging and cardiorespiratory
responses to exercise (i.e. peak
O2), we were uniquely able to examine the
correlation between elements of the GHIGF-I axis with these anatomic
and functional correlates of fitness in a relatively homogeneous
population of prepubertal girls. Following the initial baseline
measurements, the girls were randomized to either control or exercise
training groups, and we prospectively studied the effect of the 5-week
endurance-type training intervention on the growth mediators.
Materials and Methods
Sample population and protocol
Thirty-nine girls volunteered to participate in the study. The subjects were all students in the Greater Hartford elementary school district (Hartford, CT) and enrolled in a 5-week summer school program in the town of West Hartford, with class hours from 0800–1100 h (5 days per week). The ethnic configuration of the group was 77% Caucasian, 10% African American, 10% Hispanic, and 3% Asian. No attempt was made to recruit subjects who participated in competitive extramural athletic programs. The study was designed to examine pre and early pubertal subjects with an age range of 8–10 yr (mean, 9.2 ± 0.1). Measurements of height and weight were made using standard techniques. Assessment of pubertal status was performed by examination of each subject. Thirty-four (87%) of the subjects were found to be at Tanner stage I, and 6 (13%) at Tanner stage II.
The participants were randomized to a control (n = 20, 4 at Tanner II) or training group (n = 19, 2 at Tanner II). All subjects participated in a daily 45-min science program in physiology. During the remaining time, the training group members participated in two sessions of endurance-type training (45 min each) consisting of running, jumping, aerobic dance, and age-appropriate competitive sports (e.g. basketball, soccer, etc.). These two exercise sessions were separated by an elective in-class traditional course (45 min), which was selected by the study participants from the summer school curriculum. The intervention was designed to mimic the type and intensity of exercise that elementary school girls normally perform. These activities were varied in duration and intensity throughout the week, and were designed primarily as games to encourage enthusiasm and participation of the subjects. Aerobic or endurance type activities accounted for about all of the time spent in training (about 50% team sports and 50% running games). Training was directed by a physical education instructor of the West Hartford Elementary School faculty.
During the same time, the control group subjects participated in three elective in-class courses from the summer school curriculum. No attempt was made to influence extracurricular levels of physical activity in either the control or training groups, but participants were asked not to change their activity patterns from those before the study. The study was approved by the Institutional Human Subject Review Board. Informed assent was obtained from the subjects and an informed consent from their parents or guardians.
Measurements of fitness
Fitness was assessed by traditional approaches using
cardiorespiratory indices of exercise performance. The
cardiorespiratory variables were derived from measurements of peak
oxygen consumption (O2 peak) before and
after the training intervention. Each subject performed a ramp-type
progressive exercise test on a cycle ergometer in which the subject
exercised to the limit of her tolerance. Subjects were vigorously
encouraged during the high-intensity phases of the exercise protocol.
Gas exchange was measured breath-by-breath (12) and the
O2 peak was determined as previously
described for children and adolescents (13). Mean heart
rate peak was 188 ± 3 beats per minute, and mean respiratory
exchange ratio peak was 1.14 ± 0.01 suggesting that close to
maximal values were likely achieved.
Height, weight, body mass index (BMI), and muscle volume
Standard, calibrated scales and stadiometers were used to determine height, weight, and BMI. Because BMI changes with age, we calculated BMI percentile for each child using the recently published standards from the Centers for Disease Control, National Center for Health Statistics (14). Serial sections of the thigh musculature were obtained using standard magnetic resonance techniques. Computerized planimetry was used to determine thigh muscle volume as previously described in our laboratory (10).
Fitness and body size data were normalized in a number of ways to
facilitate correlation with growth mediators. For IGF-I and IGFBP-1 we
used absolute muscle volume and peak O2
because it is the amount of muscle tissue that is the major determinant
of oxygen uptake during exercise. Peak O2
normalized to body weight is an indirect estimate of muscle mass
relative to body weight (15); consequently, peak
O2 per kilogram body weight is also an
indicator of fitness when comparing subjects of different size. Peak
O2 normalized to body weight, GHBP, and
IGFPB-I were plotted against BMI percentile. Because BMI itself changes
with age, the BMI as a percentile allowed us to adequately normalize
relative fatness among the subjects of the study.
Blood sampling protocols
Subjects were admitted to the General Clinical Research Center at the University of Connecticut Health Center. An early morning fasting blood sample was collected from a forearm vein. None of the subjects trained during the day preceding the blood sampling. All pre and postintervention specimens were analyzed in the same batch by technicians who were blinded to the group and order of the samples.
GHBP
GHBP was measured using the ligand-mediated immunofunctional assay (16). Interassay coefficient of variation (c.v.) was 9.7–12.9%, and intraassay c.v. was 6.3–8.9%. Assay sensitivity was 7.8 pmol/L.
IGF-I
IGF was extracted from IGFBPs using the acid-ethanol extraction method (17). Serum IGF-I concentrations were determined by a two-site immunoradiometric assay using the DSL-5600 Active kit (Diagnostics Systems Laboratories, Inc., Webster, TX). IGF-I interassay c.v. was 3.7–8.2% and intraassay c.v. was 1.5–3.4%. Assay sensitivity was 0.8 ng/mL.
IGFBPs 1–6
IGFBP-1 and -3 were measured by coated-tube immunoradiometric assays. IGFBP-2, and -4 to -6 were measured by RIA. IGFBP-1 to -3 and -6 were measured using commercially available kits (Diagnostics Systems Laboratories, Inc.). IGFBP-4 and -5 were measured in our coauthor’s laboratory (S.M.) as recently described (18, 19). For IGFBP-1, interassay c.v. was 1.7–6.7% and intraassay c.v. was 2–4%. Assay sensitivity is 0.33 ng/mL. For IGFBP-2, interassay c.v. was 6.4% and intraassay c.v. was 6.5%. Assay sensitivity is 0.5 ng/mL. For IGFBP-3, interassay c.v. was 0.6–1.9% and intraassay c.v. was 1.8–3.9%. Assay sensitivity is 0.5 ng/mL. For IGFBP-4 interassay c.v. was less than 8.1% and intraassay c.v. was less than 5%. Assay sensitivity is less than 0.5 ng/mL. For IGFBP-5 and -6 interassay c.v. was less than 8% and intraassay c.v. was less than 4%. Assay sensitivity is less than 5 ng/mL.
Statistical analysis
Unpaired t tests were used to determine baseline
differences in circulating components of the GHIGF-I axis,
between control and training group subjects before the training
intervention. Correlation and linear regression analyses were used to
determine the correlation coefficients between elements of the
GHIGF-I axis and indices of fitness.
When the three outcome measures, GHPB, IGFBP-1, and peak
O2 per kilogram, were plotted against BMI
percentile each of the three graphics strongly suggested a threshold
effect. Based on this evidence we elected to fit each of the three
relations using a continuous, piecewise linear regression model
composed of two linear segments whose point of connection would locate
a threshold for each model. This analysis was carried out using the
SAS Nonlinear Regression Procedure (SAS Institute, Inc., Cary, NC) in which we specified a grid of
initial parameter values and then used the Marquardt method to search
for the models’ parameters, which included the threshold value. In
each case we calculated estimates for the two slope coefficients and
the threshold value together with 95% confidence limits for each of
these parameters.
Two-way repeated measures ANOVA was used to compare the effect of the
intervention on circulating components of the GHIGF-I axis
with time serving as the within-group factor and training as the
between-group factor. Statistical significance was taken at the
P less than 0.05 level. Data are presented as mean ±
SE.
Results
Height and weight
As previously reported (10), there were no significant differences in height, weight, and BMI between the groups before the intervention. Height increased to a small but significant degree in both groups during the course of the 5-week intervention (for the whole sample from 134.7 ± 1.3 cm to 135.6 ± 1.2 cm, P < 0.001), and there was no difference in the increase between control or trained subjects. Interestingly, weight increased significantly in the control subjects from 32.2 ± 2.2 kg to 32.9 ± 2.3 kg, P < 0.04), but no significant change was observed in the training group (pretraining 35.5 ± 2.3 kg, posttraining 35.7 ± 2.4 kg).
At baseline, mean BMI in the control subjects was 55 ± 7 percentile by age and did not significantly differ from training group subjects (60 ± 6 percentile). We did find a small but significant difference between the pre-post intervention change in BMI in the control (+1.3 ± 1.0%) compared with the training subjects (-1.3 ± 0.7%, P < 0.05).
Circulating components of the GHIGF-I axis:
cross-sectional data
The strongest correlations between either thigh muscle volume or
peak O2 and elements of the GHIGF-I
axis were found for IGF-I and IGFBP-1. IGF-I was significantly
correlated with both peak O2 and thigh
muscle volume (Fig. 1
). IGFBP-1 was
negatively correlated with thigh muscle volume (Fig. 2).
|
|
O2. IGFBP-6 was weakly but significantly
correlated with peak O2 (r = 0.37,
P < 0.04). GHBP was significantly correlated with body
weight (r = 0.58, P < 0.004) and with muscle
volume (r = 0.45, P < 0.02). GHBP was not
correlated with peak O2 but was inversely
correlated with the normalized peak O2 per
kilogram (r = -0.48, P < 0.007).
The relationship between body composition (estimated as BMI percentile)
and GHBP, IGFBP-1, and peak O2 per
kilogram (Table 1, Fig. 3) was revealing. The model of fitting
two straight lines (described above) suggested that there exists a
threshold value of BMI percentile above which systematic changes in
GHBP, IGFBP-1, and peak O2 per kilogram
seem to occur. There was a remarkable coincidence of the calculated
thresholds: 72, 68, and 73 percentile for GHBP, IGFBP-1, peak
O2 per kilogram, respectively. Moreover,
when the data above the threshold percentile were used, significant
correlations were found between BMI percentile and GHBP (r = 0.82,
P < 0.0003); IGFBP-1 (r = -0.80,
P < 0.003), and peak O2
per kilogram (r = -0.76, P < 0.003).
|
|
and Fig. 4)
No significant differences in elements of the GHIGF-I axis were
found between control and training group
subjects before the training intervention. Repeated measures ANOVA
revealed small but significant effects of the intervention. Significant
increases in IGF-I were noted in the control group, but there was no
significant change in IGF-I in the training subjects. IGFBP-3 declined
significantly in the training subjects, but did not significantly
change in controls. IGFBP-5 significantly increased in the control
subjects, but no significant change was observed in the training group.
Exercise training also led to a significant reduction in GHBP, with no
significant change observed in controls. No specific effect of exercise
training was observed on IGFBP-1, IGFBP-2, and IGFBP-6. IGFBP-4
increased significantly in both groups.
|
This study demonstrates that in healthy prepubertal girls,
cardiorespiratory and anatomic indices of fitness are associated with
an activated, more anabolic GHIGF-I axis. In contrast, a brief
endurance-type exercise training program seemed to have resulted in
catabolic rather than anabolic responses of the GHIGF-I system of
mediators despite the fact that training led to increased muscle volume
and improved cardiorespiratory responses to exercise. The data also
showed a remarkable relationship in healthy girls among adiposity
(judged by the BMI percentile), fitness, and indirect indicators of GH
responsiveness (i.e. GHBP) and insulin sensitivity
(i.e. IGFBP-1). It appears that above about the 68–73
percentile of BMI for age, fitness, GH levels, and insulin sensitivity
all begin to decrease even in healthy children.
In the cross-sectional analysis, IGF-I was correlated with peak
O2 and, to an even greater extent, thigh
muscle volume. These data in growing children are consistent with a
number of studies in adolescents and in adults (20, 21).
Collectively, it seems that higher levels of physical activity are
associated with increased GH pulsatility, and, eventually, with
increased circulating IGF-I. It is compelling to speculate that
stimulation of the GHIGF-I axis by exercise contributes, along with
genetic, nutritional, and other environmental factors, to an increase
in muscle mass and, ultimately, to improved cardiorespiratory responses
to exercise (such as peak O2). Our data
suggest that this mechanism operates in prepubertal girls even as
spontaneous growth proceeds.
With the exception of IGFBP-3, the amount of IGFBPs in the circulation is low, and the role of these IGFBPs in the circulation has yet to be determined. Nonetheless, it is noteworthy that our findings are consistent with current understanding of the biological activity of IGFBP-I based on tissue studies (22). IGFBP-1 and -2, known to inhibit IGF-I function, were inversely correlated with muscle mass whereas the IGF-I potentiating binding protein, IGFBP-5—recently discovered to have growth potentiating activity independent of IGF-I (23), was positively correlated with muscle mass. Accordingly, our data suggest the possibility that there may exist some combination of circulating levels of IGF-I and its binding proteins in which muscle growth and fitness are optimized in prepubertal girls.
The pattern of change of GHBP, IGFBP-1, and peak
O2 relative to BMI percentile was striking
(Fig. 3
). Increased GHBP and decreased IGFBP-1 in frankly obese
children have recently been observed (24, 25). The
decrease in IGFBP-1 may suggest the early manifestations of insulin
insensitivity because circulating levels of IGFBP-1 vary inversely with
levels of insulin. Furthermore, in obese subjects GH is known to be
suppressed without reductions in IGF-I. This finding suggests a tissue
alteration in response to the low levels of GH probably through an
increase in GH receptors. GHBP, the extracellular component of the GH
receptor, may reflect GH receptor numbers. Finally, the inverse
correlation between GHBP and peak O2 per
kilogram are consistent with BMI data. Subjects with low peak
O2 per kilogram tend to have relatively
high fat stores. GH is suppressed in these subjects and GHBP is,
consequently, elevated. Thus, GHBP was higher in the less lean girls,
those whose O2 per kilogram was low.
Fitness, independent of obesity, may also play a role in the regulation of GH and insulin sensitivity. Fitter subjects have increased GH pulsatility (21, 26, 27) and greater insulin sensitivity (28); indeed, exercise is a major treatment for type II diabetes mellitus, a syndrome characterized by profound insulin insensitivity. Our data show that there exists in healthy prepubertal girls some threshold level of adiposity that can be determined relatively easily from the BMI percentile. Above this threshold, an ominous combination of reduced fitness, low GH, and insulin insensitivity begin to manifest themselves. Such information might prove to be clinically useful in identifying children who would benefit from programs of physical activity.
Given the relatively strong correlation between IGF-I and both thigh
muscle volume and cardiorespiratory fitness, the GHIGF-I axis
response to the prospective training intervention was paradoxical,
namely, IGF-I seemed to be increasing in the control subjects but
actually fell in the trained subjects (Fig. 4). Moreover,
the apparent attenuation of IGF-I in these prepubertal children
occurred despite the fact that both thigh muscle volume and peak
O2 increased with training.
The seemingly catabolic response to the 5 weeks of training [reductions in IGF-I, IGFBP-3 and GHBP, each of which is consistent with the GH-resistant states associated with trauma and sepsis (29, 30), and an attenuation of the increase in IGFBP-5] is qualitatively similar to what we have now observed in adolescent males and females using a similar protocol (3, 31). Reductions in IGF-I associated with exercise training have been reported previously in adults and adolescents, but usually in concert with clear evidence for negative energy balance such as weight loss (1, 32) which did not occur in the present study.
Thigh muscle mass and peak O2 both
increased in the training subjects despite hormonal evidence consistent
with a catabolic state. In contrast, the small but significant
reduction in BMI in training subjects might, in the growing child,
actually indicate systemic manifestations of catabolism. We now know
that in children even a single (vigorous) exercise bout can lead to
increases in the inflammatory cytokines interleukin-6 and tumor
necrosis factor-
, both of which can inhibit IGF-I (33).
We speculate that exercise associated elevation of circulating
inflammatory cytokines leads to the reductions in IGF-I seen early in a
training program. But the mechanisms that allow particular muscle
groups to increase under these conditions, or when (and whether) there
is a rebound in the GHIGF-I axis at some point during a period of
exercise training, remain largely unknown.
Our data begin to address potential biological mechanisms related to a
number of critical issues concerning the optimal role of physical
activity and exercise training in prepubertal children. For example,
the American Academy of Pediatrics recently highlighted the potential
risks of high-intensity training and sports specialization in young
athletes but noted, "Although many concerns surround intense sports
competition in children, little scientific information is available to
support or refute these risks" (34). By examining the
effect of exercise on catabolic and anabolic mediators, it may
ultimately be possible to determine the boundary between healthy
effects of exercise (characterized, perhaps, by activation of the
GHIGF-I axis) and harmful effects (characterized by excessive tissue
cytokine and suppression of GHIGF-I activity). A scientific basis
for determining optimal levels of physical activity in children and
adolescents does not yet exist.
|
1 This work was supported by NIH Research Grants CHD26939 and
AR30162, and the General Clinical Research Grants RR00425, RR06192, and
RR00827 at University of Connecticut Health Center and at the
University of California, San Diego/University of California, Irvine
Satellite. A.E. is supported by a generous grant from the Joseph Drown
Foundation. 
Received August 24, 2000.
Revised November 29, 2000.
Revised February 8, 2001.
Accepted February 23, 2001.
References
in burned children. Arch Surg. 134:283–286.This article has been cited by other articles:
 |
|
 |
|
  A. L. Carrel, R. R. Clark, S. Peterson, J. Eickhoff, and D. B. Allen School-Based Fitness Changes Are Lost During the Summer Vacation Arch Pediatr Adolesc Med, June 1, 2007; 161(6): 561 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-K. Wu, C.-K. Wang, Y.-M. Bai, C.-Y. Huang, and S.-D. Lee Outcomes of Obese, Clozapine-Treated Inpatients With Schizophrenia Placed on a Six-Month Diet and Physical Activity Program Psychiatr Serv, April 1, 2007; 58(4): 544 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Z. Kasa-Vubu, W. Ye, K. T. Borer, A. Rosenthal, and T. Meckmongkol Twenty-Four Hour Growth Hormone and Leptin Secretion in Active Postpubertal Adolescent Girls: Impact of Fitness, Fatness, and Age at Menarche J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3935 - 3940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Eliakim, D. Nemet, F. Zaldivar, R. G. McMurray, F. L. Culler, P. Galassetti, and D. M. Cooper Reduced exercise-associated response of the GH-IGF-I axis and catecholamines in obese children and adolescents J Appl Physiol, May 1, 2006; 100(5): 1630 - 1637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Carrel, R. R. Clark, S. E. Peterson, B. A. Nemeth, J. Sullivan, and D. B. Allen Improvement of Fitness, Body Composition, and Insulin Sensitivity in Overweight Children in a School-Based Exercise Program: A Randomized, Controlled Study Arch Pediatr Adolesc Med, October 1, 2005; 159(10): 963 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Ballard, J. A Clapper, B. L Specker, T. L Binkley, and M. D Vukovich Effect of protein supplementation during a 6-mo strength and conditioning program on insulin-like growth factor I and markers of bone turnover in young adults Am. J. Clinical Nutrition, June 1, 2005; 81(6): 1442 - 1448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. T. Bloomgarden Type 2 Diabetes in the Young: The evolving epidemic Diabetes Care, April 1, 2004; 27(4): 998 - 1010. [Full Text] [PDF]
|
|
|
|
|
|
D. Nemet, P. H. Connolly, A. M. Pontello-Pescatello, C. Rose-Gottron, J. K. Larson, P. Galassetti, and D. M. Cooper Negative energy balance plays a major role in the IGF-I response to exercise training J Appl Physiol, January 1, 2004; 96(1): 276 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Nemet, Y. Oh, H.-S. Kim, M. Hill, and D. M. Cooper Effect of Intense Exercise on Inflammatory Cytokines and Growth Mediators in Adolescent Boys Pediatrics, October 1, 2002; 110(4): 681 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Adams Exercise Effects on Muscle Insulin Signaling and Action: Invited Review: Autocrine/paracrine IGF-I and skeletal muscle adaptation J Appl Physiol, September 1, 2002; 93(3): 1159 - 1167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K J MacKelvie, K M Khan, H A McKay, and C Sanborn Is there a critical period for bone response to weight-bearing exercise in children and adolescents? a systematic review * Commentary Br. J. Sports Med., August 1, 2002; 36(4): 250 - 257. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
