ORIGINAL ARTICLE

E n d o c r i n e C a r e

Effects of Continuous Versus Intermittent Exercise,

Obesity, and Gender on Growth Hormone Secretion

Arthur Weltman, Judy Y. Weltman, Dee Dee Watson Winfield, Kirsten Frick, James Patrie,
Petra Kok, Daniel M. Keenan, Glenn A. Gaesser, and Johannes D. Veldhuis
Departments of Human Services (A.W., G.A.G.), Medicine (A.W.), Public Health Sciences (J.P.), and Statistics (D.M.K.) and General
Clinical Research Center (A.W., J.Y.W., D.D.W.W., K.F.), University of Virginia, Charlottesville, Virginia 22908; and Endocrine Research
Unit (P.K., J.D.V.), Department of Medicine, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905

Context: Obesity attenuates spontaneous GH secretion and the GH response to exercise. Obese
individuals often have low fitness levels, limiting their ability to complete a typical 30-min bout of
continuous exercise. An alternative regimen in obese subjects may be shorter bouts of exercise
interspersed throughout the day.

Objective: The objective of the study was to examine whether intermittent and continuous exercise
interventions evoke similar patterns of 24-h GH secretion and whether responses are attenuated
in obese subjects or affected by gender.

Design: This was a repeated-measures design in which each subject served as their own control.

Setting: This study was conducted at the University of Virginia General Clinical Research Center.

Subjects: Subjects were healthy nonobese (n ⫽ 15) and obese (n ⫽ 14) young adults.

Interventions: Subjects were studied over 24 h at the General Clinical Research Center on three
occasions: control, one 30-min bout of exercise, and three 10-min bouts of exercise.

Main Outcome Measures: Twenty-four hour GH secretion was measured.

Results: Compared with unstimulated 24-h GH secretion, both intermittent and continuous exer-
cise, at constant exercise intensity, resulted in severalfold elevation of 24-h integrated serum GH
concentrations in young adults. Basal and pulsatile modes of GH secretion were attenuated both
at rest and during exercise in obese subjects.

Conclusions: The present data suggest that continuous and intermittent exercise training should be
comparably effective in increasing 24-h GH secretion. (J Clin Endocrinol Metab 93: 4711– 4720, 2008)

G H is secreted by the anterior pituitary gland in a pulsatile

manner under the regulation of three peptides: GHRH,
somatostatin, and GH-releasing peptide (ghrelin) (1). GHRH
fitness, and gender all influence the GH response to exercise.
Recent data from our laboratory affirm that GH secretion is
related to exercise intensity in a graded fashion (12, 16, 18).
stimulates, somatostatin inhibits, and GH-releasing peptide/gh- However, the GH response to exercise is attenuated in older
relin acts synergistically with GHRH and stimulates GH release adults (18).
directly. GH release is regulated by reversible autofeedback en- Obesity also attenuates spontaneous GH secretion as well as
forced by GH and IGF-I (1). the GH response to exercise (19 –21). Mechanistically the de-
Acute aerobic exercise is a potent stimulus to GH release crease in spontaneous 24-h GH secretion in obesity has been
(2–18). In nonobese adults, intensity and duration of exercise, attributed to a decrease in pulsatile GH release and a shorter

0021-972X/08/$15.00/0 Abbreviations: AVF, Abdominal visceral fat; BMI, body mass index; GCRC, General Clinical
Printed in U.S.A. Research Center; GM, geometric mean; IGHC, integrated serum GH concentrations; LT,
lactate threshold; VO2, O2 consumption; VO2peak, peak oxygen uptake.
Copyright © 2008 by The Endocrine Society
doi: 10.1210/jc.2008-0998 Received May 9, 2008. Accepted August 29, 2008.
First Published Online September 9, 2008

J Clin Endocrinol Metab, December 2008, 93(12):4711– 4720 jcem.endojournals.org 4711

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4712 Weltman et al. GH Secretion during Exercise
half-life of endogenous GH (22). Analogously, reduced exercise-
induced GH release in obesity has been attributed to a reduction
in the mass of GH secreted per burst (20). Many obesity-related
physical adaptations resemble those recognized in GH-deficient
adults, including reduced muscle mass and exercise capacity,
increased body fat especially abdominal visceral fat (AVF), and
increased cardiometabolic risk.
Exercise training increases spontaneous 24-h GH release in
nonobese women (13), whereas short-term aerobic exercise
training had no effect on exercise-stimulated GH release in obese
women (20). One of the concerns regarding exercise prescription
for obese individuals is their low fitness level, which may limit
their ability to complete the prescribed amount of exercise (e.g.
30 min of continuous exercise), thus restricting training effects
(23). This has led to the suggestion that multiple short bouts of
exercise interspersed throughout the day may be an effective
training strategy for less fit individuals and those who report an
inability to devote 30 – 40 min to continuous exercise due to
perceived lack of time.
Several reports indicate that an intermittent exercise regimen
is as effective as the more traditional continuous approach, par-
ticularly in obesity (23–26). This may have implications for GH
release. As few as 10 min of aerobic exercise stimulate GH release
(27) and repeated bouts of exercise during the day augment 24-h
GH release (28). Thus, the purpose of the present study was to
examine whether intermittent and continuous exercise result in
similar patterns of 24-h GH secretion and whether each response
is attenuated similarly in both exercise conditions in obese sub-
jects. We hypothesized that three bouts of intermittent exercise
would augment 24-h GH secretion compared with one bout of
continuous exercise of equal intensity and duration and mini-
mize attenuation of the 24-h GH response in obese individuals.
Subjects and Methods
Subjects and preliminary screen procedures
Twenty-nine sedentary, healthy nonobese and obese men and women
participated after providing voluntary written informed consent as ap-
proved by the Human Investigation Committee of the University of Vir-
ginia. Descriptive characteristics are presented in Table 1. Each subject
underwent a detailed medical history and physical examination. No sub-
TABLE 1. Descriptive characteristics of nonobese and obese men and women
Variable Nonobese men (n ⴝ 8)
Age (yr) 23.3 (2.0)
Height (cm) 179.5 (1.8)
Weight (kg) 76.3 (2.6)
BMI (kg 䡠 m⫺1) 23.7 (0.7)
Percentage fat 15.1 (3.1)
VO2 LT (ml/kg 䡠 min) 18.8 (1.2)
VO2peak (ml/kg 䡠 min) 38.3 (2.1)
Data are presented as mean (SE).
a
Obese is greater than nonobese (P ⬍ 0.05).
b
Obese is less than nonobese.
c
Men is greater than women (P ⬍ 0.05).
d
Men is less than women (P ⬍ 0.05).
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J Clin Endocrinol Metab, December 2008, 93(12):4711– 4720
ject had a history of hypothalamo-pituitary, renal, hepatic, hematolog-
ical, or metabolic disease. The subjects were nonsmokers, did not abuse
alcohol, and were not taking any systemic medications. Screening lab-
oratory data revealed normal hematological, renal, hepatic, metabolic,
and thyroid function. Subjects refrained from exercise for 24 h before
each evaluation. For the purposes of the present study, nonobese was
defined as a body mass index (BMI) less than 27 kg 䡠 m⫺1 and over-
weight/obese was defined as a BMI equal to or greater than 27 kg 䡠 m⫺1.
Body composition analysis
Body density was determined by hydrostatic weighing (29). Residual
lung volume was measured using an oxygen-dilution technique (30). The
computational procedure of Brozek et al. (31) was used to estimate per-
centage body fat.
Peak oxygen uptake (VO2peak) and lactate threshold
(LT) test
VO2peak and LT were evaluated via a continuous cycle ergometer
protocol. The initial power output was set at 60 W, with increases in
power output of 15 W every 3 min until volitional fatigue. Open-
circuit spirometry was used to collect metabolic data (Viasys Vmax
229, Yorba Linda, CA). Heart rate was determined electrocardio-
graphically. Blood samples were taken at rest and during the last 15
sec of each stage for the measurement of blood lactate concentration
(YSI 2700 select biochemistry analyzer; Yellow Springs Instruments,
Yellow Springs, OH). VO2 peak was chosen as the highest O2 con-
sumption (VO2) attained.
Determination of LT and the constant load
treadmill velocity
Blood lactate concentration was plotted against power output, and
LT was chosen as the highest power output obtained before the curvi-
linear increase in blood lactate concentration (32).
Exercise admissions consisted of one 30-min session (1 ⫻ 30) or three
10-min bouts (3 ⫻ 10) of exercise with power output set midway between
VO2 at LT and VO2peak.
General Clinical Research Center (GCRC) admissions
Subjects were studied at the GCRC on three randomly assigned oc-
casions, two with exercise and one at rest. Young women were tested in
the early follicular phase of the menstrual cycle. The research design is
shown in Fig. 1.
Subjects were admitted to the GCRC the evening before the studies,
consumed their evening meal by 1700 h, were allowed to consume water
ad libitum, and received a standardized snack (500 kcal, 55% carbohy-
drate, 15% protein, and 30% fat) at 2000 h. At 2100 h an iv cannula was
placed bilaterally in each forearm vein. Subjects were asked to turn lights
Nonobese women (n ⴝ 7) Obese men (n ⴝ 8) Obese women (n ⴝ 6)
25.4 (2.2) 30.6 (2.4) 29.8 (4.1)a
168.3 (2.1) 177.3 (3.1) 159.9 (2.0)b,c
66.0 (3.5) 103.6 (4.4) 97.6 (5.7)a,c
22.6 (0.8) 33.3 (2.1) 36.8 (2.5)a
27.9 (2.2) 25.6 (2.4) 46.3 (2.3)a,d
15.2 (1.9) 13.2 (1.0) 8.4 (0.7)b,c
31.0 (3.3) 28.5 (3.9) 16.1 (1.3)b,c
J Clin Endocrinol Metab, December 2008, 93(12):4711– 4720 jcem.endojournals.org 4713

Statistical analysis
To produce symmetric measurement distribu-
tions and equalize measurement, variability data
for the deconvolution parameters were trans-
formed to the natural logarithmic scale and ana-
lyzed via mixed-effects ANOVA for repeated
measures (38). The ANOVA model specification
included three classification factors to estimate
the main effect of obesity (nonobese, obese), gen-
der (female, male), and the level of the exercise
condition (control, 1 ⫻ 30 min, 3 ⫻ 10 min).
One-, two-, and three-way interactions were also
estimated.
Model parameters were estimated by way of
residual maximum likelihood, and the variance-
covariance matrix was modeled in the compound
symmetry form (39). A priori comparisons were
formulated by way of linear contrasts of the least-
squares means. Fisher’s restricted least significant
difference criterion was used to maintain an over-
all two-sided multiple comparisons type I error of
FIG. 1. Design of the present study. CHO, Cholesterol. 0.05. Confidence interval construction was based
on Fisher’s least significant difference.
For the deconvolution parameters, the within-
off by 2300 h. Beginning at 0700 h, blood samples were withdrawn every and between-group comparisons are expressed in
10 min until 0700 h the next day for later measurement of serum GH. To terms of fold change in the value of the geometric mean (GM). The GM
avoid the confounding effects of meals on GH secretion, subjects con- is a location parameter similar to the arithmetic mean and median. The
sumed standardized meals at 1000, 1400, and 1800 h and then remained value of the GM identifies the central location of the measurement dis-
fasting until the next morning. The caloric and macronutrient content of tribution and is calculated by taking the antilogarithm of the mean of the
each meal was identical (kilocalories based on measured basal metabolic distribution of logarithmically transformed data (40). We compared
rate ⫹ an activity factor, 55% carbohydrate, 15% protein, and 30% fat). GMs instead of arithmetic means because a critical statistical assumption
Subjects were asked to sit quietly in bed during the nonexercise portion of ANOVA is that, to obtain valid statistical tests, residual variation
of the day. They were allowed to read, watch television, work on their should be approximately equal within treatment groups. When the mag-
computers, and ambulate to the rest room. nitude of the variance in the response increases as the mean of the re-
sponse increases in value, the natural logarithmic transformation is gen-
erally used to stabilize the residual variance among two or more
Exercise admissions treatment groups.
The 1 ⫻ 30 min exercise bout exercise began at 0900 h and the The within- and between-group comparisons for IGHC are presented
3 ⫻ 10 min exercise bouts were initiated at 0920, 1320, and 1720 h. as a difference between the arithmetic mean. The PROC MIXED pro-
During the same time frame for each condition (9000 –1000, 1300 – cedure of SAS version 8.2 (SAS Institute Inc. Cary, NC) was used to carry
1400, 1700 –1800 h), blood lactate was measured every 10 min, heart out statistical analyses. A Bonferroni multiplier with a prespecified ex-
rate and electrocardiogram were monitored continuously, and metabolic perimental type I error rate of 0.05 was used to maintain a type I error
data were measured minute by minute during rest or exercise and during rate of 0.05.
the immediate 30 min after exercise. These assessments were made to The effects of obesity status and gender on the relationship between
assure achievement appropriate exercise intensity during the exercise IGHC and exercise condition were examined by way of a random co-
admissions and for safety reasons. efficient regression model and a random coefficient piecewise regression
model. The values for IGHC were transformed to the natural logarithmic
Nonexercise admission scale for these analyses.
Linear-mixed regression models were developed to examine the ef-
The above procedure except for exercise was followed on the non-
fects of gender and the linear and nonlinear effects of VO2 and BMI on
exercise day.
pulsatile GH at rest and during exercise.
Data are presented as mean ⫾ SE.
GH assay
GH concentrations were measured in duplicate by modified ultra-
sensitive chemiluminescence assay (Nichols Institute Diagnostics, San
Clemente, CA) using 22-kDa recombinant human GH as standard (20). Results
Cross-reactivity with 20 kDa GH was 30%. Assay sensitivity (defined as
3 SD above the zero dose tube) was 0.005 ␮g/liter. Median intra- and Nonobese individuals had lower BMI, less percentage body fat,
interassay coefficients of variation were 5.2 and 6.3%, respectively. All and greater fitness than obese individuals. Men were taller,
samples from a single subject were assayed together to eliminate inter- heavier, had lower BMI, and had less percentage body fat and
assay variability.
higher LT and VO2 peak values than women. Obese subjects
were older than nonobese subjects (P ⬍ 0.05, Table 1).
Data reduction
Assay data were analyzed by a model-free dose-dependent extrapo-
lation of triplicate standards (33). Mean and integrated serum GH con- IGHC
centrations (IGHC) were calculated (34). Hormonal secretion profiles Figure 2 shows the 10-min 24-h GH profiles from represen-
were analyzed using a recently developed deconvolution method (35–37). tative nonobese and obese male and female subjects. Each exer-

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4714 Weltman et al. GH Secretion during Exercise J Clin Endocrinol Metab, December 2008, 93(12):4711– 4720

FIG. 2. Twenty-four-hour serum GH concentration profiles sampled every 10 min in a nonobese and obese man and woman during three study sessions each (control;
a 30 min continuous bout of exercise, 1 ⫻ 30 min; three 10 min intermittent bouts of exercise, 3 ⫻ 10 min). Asterisks denote significant pulse onsets. The overlying
interrupted curves are predicted (fit) by the deconvolution model (methods). Sampling began at 0700 h (time 0). Exercise was performed at 0900 – 0930 h (single
exercise bout) and at 0920 – 0930, 1320 –1330, and 1720 –1730 h (three 10 min bouts). Standardized meals were fed at 1000, 1400, and 1800 h. Lights were put out
at 2300 h.

cise bout resulted in a GH pulse toward the end of or immediately were no differences in basal secretion among the three
after exercise, with the response attenuated in obese subjects. conditions.
Figure 3 presents the mean and SE values for 24-h integrated
GH concentrations (0700 h to 0700 h) for the three study con- GH secretory pulse frequency
ditions in nonobese and obese males and females. Significant There were no differences in GH secretory-pulse frequency
main effects were observed for obesity status (P ⬍ 0.001) and between men and women or among the three conditions. Obese
condition (P ⫽ 0.003). Within each condition 24-h IGHC in subjects had fewer detectable GH secretory pulses than nonobese
nonobese subjects exceeded that in obese individuals (P ⬍ 0.002 subjects (P ⫽ 0.007).
for all comparisons). Both exercise conditions resulted in aug-
mented 24-h IGHC compared with the resting condition (P ⫽ Slow GH half-life
0.004 for 1 ⫻ 30 min vs. control and P ⫽ 0.002 for 3 ⫻ 10 min The calculated slow GH half-life (an estimate of GH clear-
vs. control). No interactions were observed for 24-h IGHC. ance) was not affected by gender, obesity, or the three conditions.

Deconvolution analyses Pulsatile GH secretion

Table 2 presents deconvolution analyses. Twenty-four hour pulsatile GH secretion was significantly re-
duced in obese subjects (P ⫽ 0.001) and was affected by condition
Basal secretion with the 3 ⫻ 10 and 1 ⫻ 30 min conditions, resulting in greater GH
Basal GH secretion was greater in women than men (P ⬍ pulsatile secretion than the control condition (P ⬍ 0.001 and P ⫽
0.001) and in nonobese than obese subjects (P ⬍ 0.001). There 0.003, respectively).

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J Clin Endocrinol Metab, December 2008, 93(12):4711– 4720 jcem.endojournals.org 4715

FIG. 3. IGHC (0700 – 0700 h) across three exercise conditions (control; a 30 min continuous bout of exercise, 1 ⫻ 30 min; three 10 min intermittent bouts of exercise,
3 ⫻ 10 min) in nonobese and obese men and women. Data are means ⫾ SE. ANOVA revealed the following: significant main effects for obesity status (P ⬍ 0.001) and
condition (P ⫽ 0.003). Within each condition, 24-h IGHC in nonobese subjects exceeded that of obese individuals (P ⬍ 0.002 for all comparisons). Both exercise
conditions resulted in augmented 24-h IGHC compared with the control condition (P ⫽ 0.004 for 1 ⫻ 30 min vs. C and P ⫽ 0.002 for 3 ⫻ 10 min vs. C). There were
no differences observed between exercise conditions (P ⫽ 0.82), no main effect for gender, and no interactions. Capital letters give differences between exercise
conditions and lower-case letters differences among subjects (e.g. A and B indicate that 1 ⫻ 30 min and 3 ⫻ 10 min were different than control; a and b indicate that
within each condition nonobese subjects differed from obese subjects).

Mass of GH secreted per pulse
Significant main effects were observed for mass of GH se-
creted per pulse for obesity state (nonobese had greater mass of
GH secreted per pulse, P ⬍ 0.0001) and condition (the 3 ⫻ 10
min exercise condition was associated with greater mass of GH
secreted per pulse compared with control, P ⬍ 0.0001 and with
the 1 ⫻ 30 min exercise condition, P ⫽ 0.016).
Effects of gender, VO2, and BMI on pulsatile GH at rest
and during exercise
There was no effect of gender at rest or during exercise on
pulsatile GH. VO2 peak (Figs. 4 and 5, P ⫽ 0.017) and BMI (Figs.
6 and 7, P ⫽ 0.044) influenced pulsatile GH. There were signif-
icant linear trends in the relationship between VO2peak and
log(pulsatile GH) and between BMI and log(pulsatile GH) under
both the control and exercise conditions (P values ranged from
P ⫽ 0.025 to P ⬍ 0.001 for individual comparisons). The linear
trend was not condition dependent. The regression model sum-
mary examining all two-way and three-way interactions in-
dicated that at rest both VO2peak and BMI influenced pulsatile
GH (with higher VO2peak and lower BMI being associated
with elevated pulsatile GH, P ⫽ 0.02 and P ⫽ 0.04, respec-
tively) and that there was a trend for a VO2peak by BMI in-
teraction (P ⬍ 0.08). During exercise BMI (P ⬍ 0.008) but not
VO2peak influenced pulsatile GH and there was trend for a
VO2peak by BMI interaction (P ⬍ 0.07).
Discussion
Comparison of GH secretion by obesity status, gender, and con-
tinuous or intermittent exercise revealed several important find-
ings: 1) continuous and intermittent exercise were equally effec-
tive in augmenting 24-h IGHC and GH secretory profiles, 2)
obese subjects manifested marked attenuation of resting and ex-
ercise-stimulated 24-h IGHC, and 3) no gender differences were
observed for 24-h IGHC.
The present data only partially support our original hypoth-
eses. As hypothesized, both continuous and intermittent exercise
increased 24-h IGHC. However, whereas we hypothesized that
repeated intermittent exercise would augment GH secretion,
there was no difference in 24-h IGHC values between the two
exercise conditions. We based our original hypothesis on the
facts that the GH response to aerobic exercise is related to ex-

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4716 Weltman et al. GH Secretion during Exercise J Clin Endocrinol Metab, December 2008, 93(12):4711– 4720

ercise intensity (12, 16, 18); repeated bouts of aerobic exercise

60.2 (21.6)

Data are presented as mean (SE). Statistical analyses revealed: 1) basal GH secretion was greater in women than men (P ⬍ 0.001) and greater in nonobese than obese subjects (P ⬍ 0.001); 2) obese subjects had fewer detectable
GH secretory pulses (P ⫽ 0.007); 3) slow GH half-life was not affected by gender, obesity, or the control or exercise conditions; 4) 24-h pulsatile GH secretion was significantly elevated in nonobese subjects (P ⫽ 0.001) and the
9.7 (4.3)

13.8 (2.2)

13.4 (1.2)

4.3 (1.5)
3 ⴛ 10

3 ⫻ 10 min and 1 ⫻ 30 min exercise conditions compared with control (P ⬍ 0.001 and P ⫽ 0.003, respectively); and 5) nonobese subjects had greater mass of GH secreted per pulse, P ⬍ 0.0001) and the 3 ⫻ 10 min exercise
augment 24 h GH release (28); and as little as 10 min of aerobic
exercise will stimulate GH secretion (27). In earlier studies, an
Obese women (n ⴝ 6)
acute bout of aerobic exercise stimulates a large GH pulse that
typically returns to baseline with about 2 h (11, 12, 14, 16, 18,

68.0 (27.0)
5.3 (1.4)

16.7 (2.9)

13.0 (1.0)

4.1 (1.4)
1 ⴛ 30
28). Thus, we speculated that when holding total exercise dura-
tion constant, stimulating the GH axis with acute exercise three
times during the day would yield pulses that were similar to those
observed during a single bout of acute exercise, resulting in ad-
54.8 (29.4)
6.1 (2.2)

13.5 (2.2)

13.6 (1.1)

3.9 (1.7)
Control

ditional augmentation of 24-h IGHC. Subsequent to data col-

lection in the present study, we recently reported that if exercise
intensity is constant, GH release can be augmented by longer
exercise duration (41). This and diminished GH responses in
58.3 (17.0)
1.3 (0.2)

12.4 (2.0)

13.3 (1.0)

5.2 (1.6)
3 ⴛ 10

obesity may explain why intermittent exercise was not associated

with additional augmentation in 24-h IGHC.
Obese men (n ⴝ 8)

Previous findings indicate obesity attenuates both spontane-

ous and exercise-stimulated GH release (19 –21). We observed
45.5 (10.4)

condition was associated with greater mass of GH secreted per pulse compared with control, P ⬍ 0.0001 and with the 1 ⫻ 30 min exercise condition (P ⫽ 0.016).
1.2 (0.5)

15.9 (1.0)

15.8 (1.9)

2.8 (0.6)
1 ⴛ 30

similar attenuation in 24-h IGHC both at rest and in response to

continuous and intermittent exercise in obese subjects that was
not affected by gender (Fig. 3). Although we categorized obesity
in the present study based on BMI, it is likely that greater AVF
2.5 (0.9)

13.1 (1.2)

14.9 (1.6)
38.3 (8.2)

2.8 (0.5)
TABLE 2. GH deconvolution parameters for the three study conditions in nonobese and obese males and females

Control

per se is more strongly related to attenuation of spontaneous and

exercise-stimulated GH release than overall obesity. Although
we did not measure AVF, we previously reported AVF is a pri-
237.0 (48.3)

mary determinant of 24-h GH release (42). In nonobese older

25.2 (9.2)

15.9 (2.4)

13.5 (1.1)

18.9 (7.1)
3 ⴛ 10

adults stratified based on AVF levels, elevated AVF was associated

Nonobese women (n ⴝ 7)

with a marked reduction in 24-h IGHC (by 40 –50%), unfavorable

lipid and lipoprotein profiles, and an elevation in nontraditional
166.6 (21.6)

risk factors for coronary artery disease (43). Abdominal adiposity

10.9 (2.8)

16.9 (2.2)

16.3 (1.8)

10.3 (0.9)
1 ⴛ 30

rather than age and sex predicts the mass and pattern of GH secre-
tion in middle-aged adults (44) and administration of GH to obese
adults results in a greater reduction in AVF than in sc fat (45, 46).
Thus, exercise training at an appropriate intensity should elevate
148.2 (19.1)
10.2 (2.2)

15.9 (2.1)

13.4 (1.1)

10.0 (2.2)
Control

GH release (13, 16, 18) and lower AVF.

Deconvolution analysis was used to examine GH secretion
profiles (36). Exercise (of increasing intensity or duration) is
associated with an increase in the amount of GH secreted per
200.9 (37.3)

burst rather than in the number of bursts (12, 16, 18, 41). This
6.2 (1.7)

15.6 (1.8)

12.7 (1.2)

12.8 (1.2)
3 ⴛ 10

likely explains the increase in 24-h IGHC in the exercise condi-

tions because mechanistically pulsatile secretion constitutes
Nonobese men (n ⴝ 8)

most (⬎85%) of the total daily GH output (47). Importantly,

there were similar increases in 24-h IGHC within both the 1 ⫻
179.8 (31.5)
7.2 (2.5)

18.9 (1.7)

15.4 (1.5)

10.1 (1.8)
1 ⴛ 30

30 min and 3 ⫻ 10 min exercise conditions (Fig. 3). Similar to the

report of Kanaley et al. (20), our results indicate attenuated 24-h
IGHC in obese subjects was related to decreased basal and pul-
satile secretion because no differences were observed in the slow
145.8 (29.0)
4.1 (2.0)

18.1 (2.1)

13.8 (1.4)

7.41 (1.0)
Control

GH half-life, which is reflective of GH clearance. Our findings

also indicate that increased fitness (as measured by VO2peak)
elevates 24-h resting GH secretion in proportion to the elevation
of exercise-stimulated GH secretion (Figs. 4 and 5). Thus, a key
Mass/pulse (␮g 䡠 liter⫺1)

clinical goal is to enhance physical conditioning, thereby jointly

(␮g 䡠 liter⫺1 䡠 min)

(␮g 䡠 liter⫺1 䡠 min)

increasing resting and exercise-associated GH-secretion. How-

Slow half-life (min)
Pulsatile secretion
Variables

Burst frequency

ever, the fact that increased fitness cannot overcome the inhib-
Basal secretion

(n per 24 h)

itory effect of a high BMI (and presumably elevated AVF; Figs.

6 and 7) suggests that a combination of increased fitness through
an appropriate exercise program combined with a modest weight
loss program should reduce AVF 关5–10% weight loss is associ-

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J Clin Endocrinol Metab, December 2008, 93(12):4711– 4720 jcem.endojournals.org 4717

FIG. 4. Linear-mixed regression models examining the linear and nonlinear effects of VO2 (milliliters per kilogram per minute) on pulsatile GH (micrograms per liter per
24 h) at rest and during exercise in females. The solid line represents the predicted values and the dashed lines represent the simultaneous 95% confidence intervals.
There were significant linear trends in the relationship between VO2peak and log(pulsatile GH) under both the control and exercise conditions (P ⬍ 0.001 and P ⫽ 0.008
at rest and exercise, respectively). The linear trend was not condition dependent.

ated with ⬃30% reduction in AVF (48)兴 and increase GH
secretion.
The fact that both exercise conditions similarly increased
24-h IGHC may have utility in designing exercise-training pro-
grams. We have shown that traditional exercise training with
appropriate intensity can increase 24-h IGHC (13). Training
with multiple short exercise bouts distributed throughout the
day appears as effective as a single continuous exercise bout for
improving maximum VO2 and weight reduction (23–26). To our
knowledge, this is the first study to examine the effects of con-
tinuous vs. intermittent exercise on 24-h GH secretion. We were
able to control for confounding effects of caloric intake and
expenditure by serving identical meals and ensuring equal total
duration and intensity of the exercise regimens. The finding that
the 1 ⫻ 30 min and 3 ⫻ 10 min exercise conditions were com-
parably effective in increasing 24-h GH secretion in both nono-

FIG. 5. Linear-mixed regression models examining the linear and nonlinear effects of VO2 (milliliters per kilogram per minute) on pulsatile GH (micrograms per liter per
24 h) at rest and during exercise in males. The solid line represents the predicted values and the dashed lines represent the simultaneous 95% confidence intervals.
There were significant linear trends in the relationship between VO2peak and log(pulsatile GH) under both the control and exercise conditions (P ⫽ 0.016 and P ⫽ 0.025
at rest and exercise, respectively). The linear trend was not condition dependent.

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4718 Weltman et al. GH Secretion during Exercise J Clin Endocrinol Metab, December 2008, 93(12):4711– 4720

FIG. 6. Linear-mixed regression models examining the linear and nonlinear effects of BMI on pulsatile GH (micrograms per liter per 24 h) at rest and during exercise in
females. The solid line represents the predicted values and the dashed lines represent the simultaneous 95% confidence intervals. There were significant linear trends in
the relationship between BMI and log(pulsatile GH) under both the control and exercise conditions (P ⬍ 0.001 at rest and exercise). The linear trend was not condition
dependent.

bese and obese subjects (albeit the response was attenuated in
obesity) indicates that either mode of exercise should allow for
developing training programs that increase GH release. Because
intensity of exercise is directly related to GH release (12, 16, 18),
one possible advantage of multiple short bouts of exercise is the
potential to exercise at higher intensities for shorter durations.
For example, splitting a typical 30-min bout of exercise into two
15- or three 10-min bouts should allow subjects to maintain a
higher intensity of exercise over the shorter duration. This con-
cept may be particularly important for obese subjects who find
it difficult to exercise for 30 min or longer continuously. Indeed,
Jakicic et al. (23) reported that in overweight women, short bouts
of exercise enhanced exercise adherence compared with a single
bout of longer exercise.

FIG. 7. Linear-mixed regression models examining the linear and nonlinear effects of BMI on pulsatile GH (micrograms per liter per 24 h) at rest and during exercise in
males. The solid line represents the predicted values and the dashed lines represent the simultaneous 95% confidence intervals. There were significant linear trends in
the relationship between BMI and log(pulsatile GH) under both the control and exercise conditions (P ⬍ 0.001 at rest and exercise). The linear trend was not condition
dependent.

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J Clin Endocrinol Metab, December 2008, 93(12):4711– 4720
As mentioned previously, GH production is strongly and in-
versely related to AVF (42– 44). Elevated AVF is associated with
a constellation of unfavorable cardiometabolic risk factors,
which may be ameliorated by reducing visceral fat (49, 50). Ex-
ogenous administration of GH to obese men and women has
been shown to reduce AVF and improve cardiometabolic risk
factors (45, 46). Endogenous elevation of GH, as a result of
exercise training, could result in analogous reduction in AVF and
improvement in the cardiometabolic risk profile without the po-
tential for adverse events associated with GH administration.
Interestingly, the 3 ⫻ 10 min exercise condition was associated
with an elevated mass of GH secreted per pulse compared with
both the control condition and the 1 ⫻ 30 min exercise condition.
This distribution may be relevant, because an iv bolus of GH is
more effective than the same dose given continuously in eliciting
acute lipolysis (51, 52). Because both exercise conditions were
associated with elevated 24-h GH, exercise training of this type
should be associated with increased fat oxidation and glucose
and protein sparing. This in turn should be related to favorable
clinical outcomes.
We did not examine several parameters that may have influ-
enced the GH response to exercise (e.g. free fatty acids, core
temperature, IGF-I, GH binding proteins, ghrelin, etc.; for a
more complete review see Ref. 53). It could be suggested that the
difference in absolute exercise intensity may have contributed to
elevated core temperature and GH secretion in nonobese sub-
jects. However, the short duration of the exercise bouts, the fact
that all subjects exercised at the same relative intensity, and el-
evated fat content in obese subjects suggests that the physiolog-
ical stress related to exercise was similar among subjects.
In summary, compared with unstimulated 24-h GH secre-
tion, both a single 30-min and three 10-min bouts of exercise, at
constant exercise intensity, resulted in severalfold elevation in
24-h IGHC in both nonobese and obese young adults. In both
paradigms, basal and pulsatile GH secretion was attenuated both
at rest and during exercise in obese subjects. The present data
suggest that either continuous or intermittent exercise training
should be effective for increasing 24-h GH secretion.
Acknowledgments
We acknowledge the invaluable contributions of the nurses of the General
Clinical Research Center (GCRC) for drawing blood and caring for patients
and the members of the Core Laboratory for performing the assays.
Address all correspondence and requests for reprints to: Arthur
Weltman, Ph.D., Exercise Physiology Lab/Mem Gym, 210 Emmet
Street, University of Virginia, Charlottesville, Virginia 22904. E-mail:
alw2v@virginia.edu.
This work was supported by National Center for Research Resources
Grant RR-00847.
Disclosure Statement: J.Y.W., D.D.W.W., K.F., J.P., P.K., and
D.M.K. have nothing to declare. A.W. is a member of the Scientific
Advisory Boards of Kronos, and Redcord AS. G.A.G. is a consultant for
the Grains Foundation. J.D.V. is a consultant for NorvoNordisk,
Organon, and Eli Lilly Inc.
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jcem.endojournals.org 4719
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