Pituitary-adrenal-gonadal responses to high-intensity
resistance exercise overtraining
A. C. FRY,1 W. J. KRAEMER,2 AND L. T. RAMSEY1
Performance Laboratories, University of Memphis, Memphis, Tennessee 38152; and
2Center for Sports Medicine, Pennsylvania State University, University Park, Pennsylvania 16802
1Human
muscular strength; testosterone; cortisol; growth hormone;
peptide F
INCREASED TRAINING VOLUME and/or intensity, which
results in physical performance decrements, has been
defined as overtraining (12, 14, 33). The physiology of
overtraining has been studied for a variety of physical
activities (14, 33), with those emphasizing high levels
of strength or power being equally susceptible to overtraining compared with other types of activities (14). In
general, the physiological mechanisms of overtraining
have only recently been elucidated. Although much has
yet to be learned regarding the etiology of overtraining,
it appears to be quite different when anaerobic activities, such as resistance exercise, are compared with
aerobic activities (12, 13). Many of the overtraining
symptoms identified for aerobic exercise, such as alterations in sleep patterns, resting heart rates, mood
states, and sympathetic activity, have not been reported for anaerobic overtraining protocols (12, 13).
Furthermore, altering some of the acute training variables for resistance exercise (i.e., volume of exercise,
rest intervals, and load) results in a variety of different
physiological responses (30). Thus it is likely that
overtraining resulting from distinctly different resistance exercise programs may be characterized by different physiological responses.
Increased volumes of aerobic exercise (3, 34) and
resistance exercise (11, 18, 19) have resulted in decreased concentrations of several hormones at rest.
Recent research on the effects of increased resistance
exercise relative training intensity (i.e., percentage of
maximum) (12, 13) indicates that this type of training
stress may be quite different physiologically from increased resistance exercise training volumes. Few resistance exercise training studies have demonstrated
actual performance decrements (34); thus overtraining
is not present in many investigations. In general, little
data are available on the endocrine responses to resistance exercise overtraining and its concomitant performance decrements.
Previous endocrine research with increased resistance exercise training stress has monitored only resting hormonal concentrations (18). It has been proposed
that the exercise-induced endocrine responses reflect
different hormonal regulatory mechanisms (14), and
recent investigations have included exercise-induced
endocrine responses (11, 17, 19). Changes in circulating
hormonal concentrations have been proposed as indicators of overtraining (1, 14), although such hormonal
changes are not always observed. Because fluctuations
in strength performance have been associated with
altered resting (16, 18) and exercise-induced (27) endocrine profiles with resistance exercise, it is possible that
changes in hormonal concentrations may serve as
markers of an impending state of overtraining.
Recently, an exercise protocol has been developed for
producing short-term muscular strength decrements
with low-volume (i.e., sets 3 repetitions), high-relativeintensity [i.e., percentage of 1-repetition maximum
(%1-RM)] resistance exercise (12, 13). Although not
intended as a training method for optimal performance,
this protocol was designed specifically to elicit an
overtraining response, thus allowing physiological study
of the development of this phenomenon. Therefore, the
purpose of this investigation was to determine whether
overtraining due to high relative intensity (%1-RM)
resistance exercise results in altered resting and exercise-induced circulating hormonal concentrations.
METHODS
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.
2352
Subjects. Seventeen men were randomly divided into either
an experimental group who overtrained by using high relative
weight training intensities (OT; n 5 11) or a control group who
used lower relative weight training intensities (Con; n 5 6).
8750-7587/98 $5.00 Copyright r 1998 the American Physiological Society
http://www.jap.org
Downloaded from http://jap.physiology.org/ by 10.220.33.6 on June 17, 2017
Fry, A. C., W. J. Kraemer, and L. T. Ramsey. Pituitaryadrenal-gonadal responses to high-intensity resistance exercise overtraining. J. Appl. Physiol. 85(6): 2352–2359, 1998.—
Weight-trained men [OT ; n 5 11; age 5 22.0 6 0.9 (SE) yr]
resistance trained daily at 100% one-repetition maximum
(1-RM) intensity for 2 wk, resulting in 1-RM strength decrements and in an overtrained state. A control group (Con; n 5
6; age 5 23.7 6 2.4 yr) trained 1 day/wk at a low relative
intensity (50% 1 RM). After 2 wk, the OT group exhibited
slightly increased exercise-induced testosterone (preexercise
5 26.5 6 1.3 nmol/l, postexercise 5 29.1 6 5.9 nmol/l) and
testosterone-to-cortisol ratio (preexercise 5 0.049 6 0.007
nmol/l, postexercise 5 0.061 6 0.006 nmol/l) and decreased
exercise-induced cortisol (preexercise 5 656.1 6 98.1 nmol/l,
postexercise 5 503.1 6 39.7 nmol/l). Serum concentrations for
growth hormone and plasma peptide F [preproenkephalin
(107—140)] were similar for both groups throughout the
overtraining period. This hormonal profile is distinctly different from what has been previously reported for other types of
overtraining, indicating that high-relative-intensity resistance exercise overtraining may not be successfully monitered via circulating testosterone and cortisol. Unlike overtraining conditions with endurance athletes, altered resting
concentrations of pituitary, adrenal, or gonadal hormones
were not evident, and exercise-induced concentrations were
only modestly affected.
PITUITARY-ADRENAL-GONADAL RESPONSES
Table 1. Subject characteristics of the overtraining and
control groups during test 1
Variable
OT
Con
n
Age, yr
Height, cm
Body mass, kg
Relative fat, %
Lean body mass, kg
Leg weight training experience, yr
11
22.0 6 0.9
176.6 6 2.1
83.4 6 4.9
12.2 6 1.9
72.2 6 2.5
4.0 6 1.0
6
23.7 6 2.4
175.7 6 3.1
81.2 6 5.6
10.0 6 2.1
72.7 6 4.3
5.7 6 2.5
Values are means 6 SE; n, no. of men. OT, overtraining group; Con,
control group. Values did not significantly change during the course
of the investigation, P . 0.05.
RM) exercise protocol on the squat machine each day; this has
been shown to elicit an overtraining response characterized
by muscular strength decrements (12, 13). Conversely, the
Con group performed a low-volume, low-relative-intensity
protocol 1 day/wk, designed to maintain muscular strength
and to not result in an overtraining syndrome.
The resistance exercise and strength test protocols used in
the present investigation have been previously described in
detail (12, 13) and are presented in Fig. 1. Briefly, it was the
objective of each exercise session for the OT group to perform
resistance exercise at a maximal relative intensity (100% 1
RM) by performing 10 single repetitions at 100% of their 1
RM on the squat machine with 2 min of timed rest between
each attempted lift. When a weight could not be lifted, the
resistance for subsequent repetitions was decreased by 4.5
kg. The net result was that each of the 10 successful lifts was
performed as close to each subject’s maximal capability as
possible. Each training session began with a controlled
warm-up, followed by a 1-RM assessment from which the
subsequent resistances were based for that day. This exercise
protocol was not meant to mimic traditional training programs used to optimize strength performance but was instead
a tool used to elicit an overtraining response with concomitant performance decrements. One exercise session per week
was performed by the Con group to allow them to remain
familiar with the exercise in a nonstressful manner that
would maintain muscular strength throughout the study. A
second day each week was devoted to 1-RM testing for the
Con group. All exercise sessions for both groups were supervised by at least one member of the research team.
Test batteries were administered at the beginning (test 1),
middle (test 2), and end of the 2-wk overtraining period (test
3). During each test battery, sets of 10 continuous repetitions
at 70% of the current 1-RM load were performed until
exhaustion, with 1 min of rest between each set. This test
served as the exercise stimulus around which resting and
exercise-induced hormonal concentrations were monitored;
therefore, the time of day for each of these tests was kept
constant for each subject to minimize diurnal endocrine
variations.
Blood sampling. On reporting for the 70% 1-RM test
session, all subjects were placed in a seated position similar to
the terminal position on the squat machine. A 20-gauge,
3.2-cm Teflon intravenous catheter was inserted in a superficial antecubital vein. The cannula was kept patent with a
continuous saline drip (0.9% sodium chloride) at a rate of ,45
ml/h. A four-way stopcock was placed in line with the saline
drip to permit blood sampling with syringes. A 6-h fast
preceded this test session, although subjects were allowed
water ad libitum. The subjects remained calmly in their
Fig. 1. Exercise session and testing
session timeline for the overtraining
(OT) and control (Con) groups. Test
battery 1, beginning of 2-wk overtraining period; test battery 2, middle of 2-wk
overtraining period; test battery 3, end
of 2-wk overtraining period. 1 RM, 1
repetition maximum; Exer, exercise;
Quad, quadriceps. *Refers to details in
bottom part of figure.
Downloaded from http://jap.physiology.org/ by 10.220.33.6 on June 17, 2017
All subjects had performed weight training for the legs for a
mean of 4.5 yr, were capable of at least a 1.5 3 body weight 1
RM for the parallel barbell back squat, had been consistently
training immediately before participating in this investigation, and had no history of anabolic steroid use over the
previous year. Each subject was apprised of the risks of
participation and signed an informed consent statement.
These same subjects have been previously described in studies examining performance decrements and catecholamine
responses to high intensity resistance exercise overtraining
(12, 13). Subject characteristics for both groups are listed in
Table 1.
Resistance exercise and testing protocols. Lower body training was performed on a squat resistance exercise machine
(Southern Xercise, Cleveland, TN). Kinematic characteristics
of exercise on this particular squat machine indicate that this
exercise is not identical to barbell squats but does instead
primarily involve extension at the hips and knees (9). This
device was chosen for this study because it utilized an easily
learned gross motor pattern involving a large-muscle-group,
multijoint activity, within a regulated joint range of motion.
Safety of the subject was enhanced because a single person
could easily spot maximal lifts in the event of a failed
repetition. This machine has also been used in previous
longitudinal resistance training studies (12, 13). Lower body
resistance exercise was controlled in the present study while
current upper body resistance exercise programs were held
constant for the duration of the training period. All subjects
participated in a 1-wk familiarization phase. Two familiarization sessions were used to acquaint the subjects with proper
exercise technique and to perform 1-RM assessments. One-RM
test reliability determined from the two familiarization sessions was r 5 0.96. Exercise sessions on the squat machine
were performed during weeks 2 and 3 of the study. The OT
group performed a low-volume, high-relative-intensity (%1-
2353
2354
PITUITARY-ADRENAL-GONADAL RESPONSES
vaspec II, Uppsala, Sweden). Exercise-induced plasma volume shifts (%) were estimated from changes in hematocrit
and hemoglobin by using the methods of Dill and Costill (6).
Statistical analyses. All data are presented as means 6 SE.
Independent t-tests were used to compare descriptive characteristics of each group. Physical performances were analyzed
with 2 3 3 (group 3 test) mixed-model ANOVAs. Blood
variables were analyzed with 2 3 3 3 3 (group 3 time 3 test)
mixed-model ANOVAs. All ANOVAs were adjusted for unequal sample sizes. Post hoc analyses were performed with
Fisher’s least significant difference procedures. The use of
parametric statistics for all endocrine-dependent variables
was supported by the lack of significance for both the Kolmogorov-Smirnov test for normality of distributions and the
Bartlett test for homogeneity of variances. Significance was
P , 0.05 for all analyses.
RESULTS
During the course of the investigation, descriptive
characteristics did not change from the values listed in
Table 1 for either the OT or the Con groups. One-RM
lifting capabilities for the OT group significantly decreased ,11% compared with the Con group (OT,
mean 5 212.2 kg; Con, mean 5 21.1 kg) as previously
reported (12). The Con group exhibited no significant
changes in 1-RM strength, indicative of the efficacy of
their training protocol for maintaining training-specific
(1-RM) strength.
The results for total testosterone, free testosterone,
percent unbound testosterone, and cortisol (Fig. 2);
total testosterone-to-cortisol ratio and free testosteroneto-cortisol ratio (Fig. 3); growth hormone (Fig. 4); and
peptide F and its molar ratio with epinephrine (Fig. 5)
are illustrated in their respective figures. No anticipatory response (Pre 1 vs. Pre 2) was evident for any
variable at any time. Testosterone, free testosterone,
and growth hormone exhibited significant exerciseinduced increases for most tests for both groups. The
OT group had slightly elevated postexercise total testosterone concentrations by test 3, whereas the Con group
exhibited increased concentrations of total testosterone
at both rest and postexercise by test 3. No differences
for percent unbound testosterone were observed across
time for either group or between groups at any time. No
changes in resting concentrations of cortisol were observed for either group, and exercise produced no
significant increases, although postexercise cortisol for
the OT group had decreased slightly by test 3.
Figure 3 illustrates the responses of total testosteroneto-cortisol ratio and free testosterone-to-cortisol ratio.
The postexercise ratio of total testosterone to cortisol
increased slightly for the OT group at test 3, although
the preexercise values were less than for the Con group
for this test. This difference between groups appeared
to be due to elevated total testosterone concentrations
for the Con group rather than to decreased total
testosterone for the OT group. Few differences were
observed between groups for free testosterone-tocortisol ratio. Growth hormone exhibited similar exercise-induced increases for all three tests, but no differences were observed between the OT and Con groups.
Downloaded from http://jap.physiology.org/ by 10.220.33.6 on June 17, 2017
seated position for 30 min. During this time, blood samples
were taken after 15 (Pre 1) and 30 min (Pre 2). This was
immediately followed by the 70% 1-RM test for repetitions.
Immediately on completion of the 70% 1-RM test for repetitions, a postexercise blood sample was taken for determination of peptide-F concentrations. The subjects were then
seated for 5 min, after which a final blood sample was taken (5
min) for determination of the remaining exercise-induced
hormonal concentrations.
Blood sample preparation. Ten milliliters of whole blood
from each sample time were allowed to clot at room temperature and then were centrifuged at 1,500 g and 4°C for 15 min.
The resulting serum was aliquoted for subsequent analysis of
total testosterone, free testosterone, cortisol, and growth
hormone. Peptide-F concentrations were determined from a
3-ml whole-blood sample that was immediately placed into a
chilled glass test tube (4°C) containing EDTA (3 mg) and
aprotinin (1,500 kallikrein-inactivating units). Plasma for
analysis of peptide F was aliquoted after centrifugation for 15
min at 1,500 g at 4°C. One milliliter of whole blood was mixed
with heparin sodium, from which a small portion was used to
determine hematocrit by using standard microcapillary techniques. The remaining portion was saved for subsequent
analysis of total hemoglobin. All aliquots not immediately
analyzed were stored at 290°C for future analysis. Samples
were thawed only once for analysis and were decoded after all
analyses were completed (blinded format).
Blood analyses. Single-antibody, solid-phase radioimunoassays were used to determine imunoreactivity levels indicative
of blood concentrations of testosterone and free testosterone
(Diagnostic Products, Los Angeles, CA), and cortisol (Diagnostic Systems, Webster, TX). Radioimunoreactivity was measured with an LKB 1272 Clinigamma automatic gamma
counter and data reduction package (Pharmacia LKB Nuclear,
Turku, Finland). Variances for the radioimunoassays performed in this investigation were as follows: total testosterone (intra-assay #2.5%, interassay 5 3.0%), free testosterone
(intra-assay #2.5%, interassay 5 9.6%), and cortisol (intraassay #3.8%, interassay 5 3.2%). Hormonal concentrations
were determined at each sampling time for testosterone-tocortisol and free testosterone-to-cortisol ratios. The percent
unbound testosterone was determined from the total testosterone and free testosterone data for each sampling time. An
immunoradiometric assay was used for the determination of
growth hormone concentrations (Nichols Institute Diagnostics, San Juan Capistrano, CA). All samples were analyzed in
duplicate with intra-assay variance of #3.7% and interassay
variance of 3.0% for growth hormone. Peptide F was separated from plasma by using a C18 (200-mg) separating column
(Peninsula Laboratories, Belmont, CA) and a series of washes
(0.1% trifluoroacetic acid and 60% acetonitrate in 0.1% trifluoroacetic acid). The resulting eluent (3 ml) was then evaporated to dryness by a centrifugal concentrator. Peptide-F
concentrations were then measured by using a 3-day doubleantibody, liquid-phase 125I radioimmunoassay (Peninsula
Laboratories). All samples were analyzed in duplicate with
intra-assay variance of #6.1% and interassay variance of
14.0%. The recovery of peptide F was 85.9%, and the coefficient of regression for the standard concentrations was 0.991.
Peptide-F values were then compared with previously reported epinephrine concentrations (13). The molar ratio
between circulating peptide-F and epinephrine concentrations was calculated for each sampling time. Changes in the
molar ratio over time would suggest different secretory
patterns for peptide F and epinephrine. Total whole-blood
hemoglobin was determined with a quantitative, calorimetric
determination at 540 nm (Sigma Diagnostics, St. Louis, MO)
by using a visible spectrophotometer (Pharmacia LKB No-
PITUITARY-ADRENAL-GONADAL RESPONSES
2355
Fig. 3. Resting and exercise-induced responses
of the testosterone-to-cortisol and free testosterone-to-cortisol ratios for both OT (n 5 11
men) and Con (n 5 6 men) groups. Values are
means 6 SE. Brackets represent time points
compared. * Con and * OT, difference between
tests, P , 0.05. * Difference between groups,
P , 0.05.
Downloaded from http://jap.physiology.org/ by 10.220.33.6 on June 17, 2017
Fig. 2. Resting and exercise-induced responses
for testosterone, free testosterone, percent
unbound testosterone, and cortisol for both
OT (n 5 11 men) and Con (n 5 6 men) groups.
Values are means 6 SE. Pre 1, 15 min preexercise; Pre 2, immediately preexercise; 5 min, 5
min postexercise. Brackets represent time
points compared. * Con and * OT, difference
diference between tests, P , 0.05. 1 Different
from Pre 1 and Pre 2, P , 0.05.
2356
PITUITARY-ADRENAL-GONADAL RESPONSES
Fig. 4. Resting and exercise-induced responses
of growth hormone for both OT (n 5 11 men)
and Con (n 5 6 men) groups. Values are
means 6 SE. 1 Different from Pre 1 and Pre 2,
P , 0.05.
DISCUSSION
Performance decrements. The overtraining exercise
protocol used in the present study resulted in significant decrements in 1-RM leg strength (12), indicative of
a state of overtraining (14, 33). This phenomenon did
not appear to be transient, because OT subjects reported an inability to resume their normal resistance
training loads for up to 8 wk after this study, thus
requiring a long-term regeneration period. As previously reported, the decreased strength performances
for the OT group did not appear to be due to muscle
damage, as indicated by serum levels of total creatine
kinase or perceptions of muscular soreness (12). Decreased strength performances were a result of the
high-relative-intensity training for only the lower body
because upper body training was held constant at
normal levels for all subjects. Although the onset of
overtraining by increased training volume has been
studied in endurance athletes (34), previous investigations have not monitored endocrine profiles accompanying the onset of overtraining with high-relativeintensity (%1-RM) resistance exercise. The hormonal
profile observed in the present study was markedly
different from what has been indicated for other types
of overtraining and was generally not altered due to the
present overtraining protocol.
Total testosterone. Although increased volumes of
weight training generally result in decreased resting
and exercise-induced (11, 15, 28) total testosterone
levels, the increased relative training intensity used by
the OT group did not alter preexercise concentrations
of total testosterone and actually slightly increased the
acute response. On the other hand, the Con group
exhibited increased preexercise total testosterone by
test 3, which has been observed before with decreased
training stress (15). The increased total testosterone
concentrations were greater than the plasma volume
shifts, suggesting that increased testosterone secretion
and/or decreased clearance was responsible for the
exercise-induced responses. Exercise-induced testosterone responses are apparently not under hypothalamicpituitary regulation via leutinizing hormone (19). In
the present study, the acute testosterone increases
were not accompanied by elevated luteinizing hormone
concentrations (unpublished observations), although
these data are preliminary because they do not account
for pulsatility characteristics. The elevated exerciseinduced sympathetic activity previously been reported
for the OT group (13) most likely contributed to the
augmented acute testsoterone response (7, 23). The
augmented exercise-induced total testosterone response with overtraining at test 3 may have been part of
an unsuccessful physiological attempt to preserve muscular strength capabilities. Although it is unclear as to
the exact mechanism responsible, the relatively low
volume of resistance exercise for the OT group may
have kept total testosterone from decreasing, contrary
to what has been observed with studies of increased
resistance training volume (11, 15, 28).
Free testosterone. Normal resistance exercise training programs increase resting free testosterone concentrations (2, 18), whereas increased training volumes
result in attenuated resting (16, 18, 19) and augmented
acute (19) free testosterone. It has been theorized that
free testosterone is more sensitive to the stresses of
overtraining than is total testosterone (16). Contrary to
this suggestion, at no time did the OT protocol in the
present study affect concentrations of free testosterone
at any sampling time. Exercise-induced increases in
free testosterone were usually evident and remained
constant throughout the study.
Percent unbound testosterone. No changes were observed in the percent unbound testosterone, which is
Downloaded from http://jap.physiology.org/ by 10.220.33.6 on June 17, 2017
Peptide-F concentrations for the OT and Con groups
were similar for all tests, and no changes were reported
for either group at any sampling time. Molar ratio
values between peptide F and previously reported
epinephrine values (13) were not different between the
OT and Con groups. For all tests, there was a significant decrease in molar ratio from both preexercise
samples (Pre 1 and Pre 2) to immediately postexercise.
Mean estimated exercise-induced plasma volume
shifts for all subjects and tests were 215.9%. This
indicates that the nonsignificant exercise-induced increases of cortisol can be accounted for by plasma
volume shifts. Total testosterone, free testosterone, and
growth hormone all exhibited exercise-induced concentration increases greater than what can be attributed
to plasma volume shifts alone. Although hormonal
concentrations can be adjusted for plasma volume
shifts (38), this only accounts for one of many regulating mechanisms (30). Because the present study was
concerned only with actual circulating hormonal concentrations, and not hormonal kinetics, concentrations
were not adjusted for plasma volume shifts, thus
permitting comparison with previous overtraining research.
PITUITARY-ADRENAL-GONADAL RESPONSES
2357
Fig. 5. Resting and exercise-induced responses
of peptide F and molar ratio of peptide F to
epinephrine for both OT (n 5 11 men) and Con
(n 5 6 men) groups. Values are means 6 SE.
1 Different from Pre 1 and Pre 2, P , 0.05.
because they do not account for pulsatility characteristics. Evidence exists of neural control of adrenal cortex
activity (22), thus providing a rapid regulatory mechanism of exercise-induced cortisol responses. It is not
known, however, whether altered adrenal cortex activity, sympathetic nervous system regulation, or some
other physiological mechanism is responsible for the
decreased exercise-induced cortisol response of the OT
group.
Hormonal ratios. It has been suggested that the total
testosterone-to-cortisol ratio may be a marker for overtraining with resistance exercise (18). Exercise-induced
total testosterone-to-cortisol ratio usually decreases
postexercise (10, 11). When resistance exercise training
volume is increased, resting and exercise-induced total
testosterone-to-cortisol ratio will typically decrease (10,
16, 18), although this pattern is reversed with longterm training and prior exposure to elevated training
volumes (10). No decreases of total testosterone-tocortisol ratio were observed in the present study, and
differences between the OT and Con groups for resting
ratios were due primarily to augmented total testosterone for the Con group only. The resting ratio of biologically available testosterone (i.e., free testosterone) and
cortisol (free testosterone-to-cortisol ratio) does not
change with normal resistance exercise training volumes or detraining (2). In the present study, few
changes in resting or exercise-induced free testosteroneto-cortisol ratio values were observed for either group.
Although the OT group experienced performance decrements, decreases in free testosterone-to-cortisol ratio of
$30%, or values below 0.35 3 1023, were not observed
at any time, contrary to the overtraining markers
suggested by Adlercreutz et al. (1). In contrast to
reports of endurance activities, neither the testosteroneto-cortisol ratio nor the free testosterone-to-cortisol
ratio seems to be an effective marker of high-intensity
resistance exercise overtraining.
Growth hormone. No previous resistance exercise
overtraining research has monitored growth hormone
responses. The present data suggest that growth hor-
Downloaded from http://jap.physiology.org/ by 10.220.33.6 on June 17, 2017
the fraction of total testosterone that is classified as
free testosterone. This indicates that changes for testosterone-binding proteins, such as sex hormone-binding
globulin (SHBG) and albumin, simply mirrored the
changes in circulating total testosterone. It has been
suggested that increased free testosterone occurs with
exhaustive exercise to compensate for decreased total
testosterone concentrations (1). Because it is the unbound fraction of total testosterone that is available for
biological activity at the target receptors, this would be
an effective method for maintaining the biological
activity of testosterone in the presence of decreased
total testosterone concentrations (28). This, however,
was not evident in the present study. The lack of change
for percent unbound testosterone was not unexpected
because the association constant for SHBG does not
change due to an acute exercise bout (7).
Cortisol. Long-term normal resistance exercise programs result in no change or decreased resting (2, 18)
and increased exercise-induced cortisol concentrations
(29). Contrary to studies of increased resistance training volume (11, 16, 18), the overtraining protocol used
in the present study produced no changes in preexercise cortisol concentrations. Of particular interest are
the decreased exercise-induced cortisol concentrations
for the OT group by test 3, similar to what is seen with
increased training volumes (11). The exercise-induced
cortisol responses were at all times comparable to or
less than the plasma volume shifts, indicating a lack of
adrenal cortical response to the exercise stimulus and
suggesting that exercise duration may have been too
short in the present study (4). It is unlikely that
hypothalamic-pituitary regulation via adrenocorticotropic hormone is responsible for the attenuated exercise-induced cortisol response, because the lag time for
adrenocorticotropic hormone activation of cortisol is
much longer than the cortisol sampling period used in
the present study (8). This is further supported by the
absence of any changes in adrenocorticotropic hormone
levels over the course of the present study (unpublished
observations), although these data are preliminary
2358
PITUITARY-ADRENAL-GONADAL RESPONSES
(31, 32), is not known. It should be noted that the
half-life (t½ ) for peptide-F plasma clearance after secretion from the chromaffin cells is $15 min (24), which
allows considerable time for peptide F to interact at its
primary site of action, in the circulation (35, 40). The
use of a sampling time immediately postexercise was
rapid enough to avoid problems with differences in
clearance t½ between peptide F and epinephrine, and
was appropriate for determining peak postexercise
concentrations of peptide F (31, 32). It should be noted
that there is no known change in the clearance rate of
peptide F due to exercise intensity or modality (31).
Overtraining markers. Previous research has attempted to identify endocrine markers of an impending
or concurrent overtraining syndrome for both aerobic
(1, 3, 34) and anaerobic activities (18). Because of the
lack of association between endocrine and performance
alterations, the type of exercise employed in the present study does not readily permit use of hormonal
alterations to monitor impending overtraining. The
daily exercise protocol used by the OT group (i.e., high
relative intensity, low volume) may not acutely activate
testicular or adrenal cortex activity to a great extent, as
has been demonstrated with a similar resistance exercise protocol (17). This may partly explain the lack of
endocrine adaptations to the OT protocol. Therefore,
other physiological systems, such as sympathetic nervous system activity (13) or neuromuscular characteristics (12), may need to be monitored to avoid overtraining with short-term, high-intensity resistance exercise
with subjects who have previously weight trained.
Previous resistance exercise investigations have demonstrated significant positive correlations between changes
for free testosterone (2, 18), total testosterone-tocortisol ratio (19), or free testosterone-to-cortisol ratio
(2), and changes for physical performances such as
isometric quadriceps force (2, 19), clean-and-jerk 1 RM
(18), or a calculated fitness index (5). No such correlations were evident for the OT group (unpublished
observations).
Summary. Circulating testosterone, free testosterone, cortisol, growth hormone, and peptide-F concentrations were not greatly affected by the high-intensity
exercise protocol for the OT group. Although decrements in strength performance were readily apparent,
these changes were not accompanied by an altered
hormonal environment for the OT group. It appears
that short-term, high-relative-intensity resistance exercise overtraining may not be successfully monitored via
circulating hormonal concentrations.
The authors extend their appreciation to N. Travis Triplett, L.
Perry Koziris, Joseph L. Marsit, Femke van Borselen, and J. Michael
Lynch for assistance with the data collection and to Steven J. Fleck,
Robert S. Staron, and Anne B. Loucks for assistance with the
hormonal analyses.
Address for reprint requests: A. C. Fry, 135 Roane Field House,
University of Memphis, Memphis, TN 38152.
Received 15 April 1998; accepted in final form 23 July 1998.
REFERENCES
1. Adlercreutz, H., M. Härkönen, K. Kuoppasalmi, H. Näveri,
I. Huhtaniemi, H. Tikkanen, K. Remes, A. Dessypris, and J.
Karvonen. Effect of training on plasma anabolic and catabolic
Downloaded from http://jap.physiology.org/ by 10.220.33.6 on June 17, 2017
mone is not influenced by high-intensity resistance
exercise overtraining. Although Barron et al. (3) have
reported hypothalamic-pituitary dysfunction with aerobically based overtraining, and Urhausen et al. (39)
have recently reported attenuated acute growth hormone responses to endurance overtraining, the present
data do not indicate altered growth hormone concentrations accompany high-intensity resistance exercise overtraining.
Peptide F. Peptide F [preproenkephalin (107—140)]
is secreted from the adrenal medullary chromaffin cells
and is often secreted in response to the same exercise
stimuli that cause epinephrine release (31). Previous
research has indicated that, although chronic highintensity interval and endurance training in collegiate
runners results in augmented acute epinephrine concentrations, acute peptide-F concentrations were attenuated, suggesting that epinephrine and peptide F are not
released in equimolar fashion in highly trained elite
endurance runners (31). This was in contrast to untrained individuals who exhibited equimolar acute
concentrations of circulating peptide F and epinephrine
(31). This difference in acute circulating concentrations
suggests a possible training adaptation in the production and/or secretory mechanisms of the adrenal chromaffin cells. Peptide F may play a role in regulating the
immune response via natural killer cell regulation,
neutrophil activation, and coagulation enhancement
(21, 35, 40). Such a stimulatory effect on the immune
system may counter the immunosuppressive effects of
catecholamines and glucocorticoids (21), both of which
are elevated with various types of overtraining (13, 14,
33). This immunosuppression may partly explain why
overtraining is associated with increased rates of infection (14, 33).
No previous studies have recorded the response of
peptide F to resistance exercise overtraining. The previously reported increases in acute epinephrine due to
this overtraining protocol (13) were not observed for
peptide F. These data suggest that peptide F and
epinephrine were not secreted in equimolar concentrations due to this overtraining protocol, as indicated by
the significant decrease for the exercise-induced molar
ratios. The extremely large epinephrine response to the
high-intensity resistance exercise overtraining (13) may
have simply overwhelmed the capacity of the adrenal
medullary chromaffin cells to secrete peptide F. This
also suggests that the requirement for peptide F under
these stressful conditions is less than for epinephrine.
The absence of an acute peptide-F response could be
due to an inadequate exercise stimulus (e.g., duration
too short, inadequate work production), as has been
previously reported (32), or due to the fact that all of the
subjects were previously weight trained, which may
have attenuated the acute peptide-F response that has
been reported for highly trained endurance runners
(31). Whether the lack of peptide-F response is due to
the slower processing of peptide F from its precursor
molecule compared with epinephrine (26, 37), or
whether there are chromaffin cell pools that may
contain different ratios of peptide F and epinephrine or
may preferentially secrete one particular compound
PITUITARY-ADRENAL-GONADAL RESPONSES
2.
3.
4.
5.
6.
7.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22. Holzwarth, M. A., L. A. Cunningham, and N. Kleitman. The
role of adrenal nerves in the regulation of adrenocortical function. Ann. NY Acad. Sci. 512: 449–464, 1987.
23. Jezova, D., and M. Vigas. Testosterone response to exercise
during blockade and stimulation of adrenergic receptors in man.
Horm. Res. 15: 141–147, 1981.
24. Katzenstein, G. E., D. Lund, P. Schultz, and R. V. Lewis.
Target tissue distribution of the proenkephalin peptides
F, E and B. Biochem. Biophys. Res. Commun. 146: 184–1190,
1987.
25. Kilpatrick, D. L., R. V. Lewis, S. Stein, and S. Undenfriend.
Release of enkephalins and enkephalin-containing polypeptides
from perfused beef adrenal glands. Proc. Natl. Acad. Sci. USA 77:
7473–7475, 1981.
26. Kopin, I. J. Catecholamine metabolism (and the biochemical
assessment of sympathetic activity). Clin. Endocrinol. Metab. 6:
525–549, 1977.
27. Koziris, L. P., A. C. Fry, W. J. Kraemer, M. H. Stone, J. T.
Kearney, S. J. Fleck, J. Thrush, S. E. Gordon, and N. T.
Triplett. Hormonal and competitive performance responses to
an over-reaching stimulus in elite junior weightlifters (Abstract).
J. Appl. Sports Sci. Res. 6: 186, 1992.
28. Kraemer, W. J. Hormonal mechanisms related to the expression
of muscular strength and power. In: Strength and Power in Sport,
edited by P. V. Komi. London: Blackwell Scientific, 1992, p.
64–76.
29. Kraemer, W. J., A. C. Fry, B. J. Warren, M. H. Stone, S. J.
Fleck, J. T. Kearney, B. P. Conroy, C. M., Maresh, C. A.
Weseman, N. T. Triplett, and S. E. Gordon. Acute hormonal
responses in elite junior weightlifters. Int. J. Sports Med. 13:
103–109, 1992.
30. Kraemer, W. J., L. Marchitelli, S. E. Gordon, E. A. Harman,
J. E. Dziados, R. Mello, P. N. Frykman, D. McCurry, and
S. J. Fleck. Hormonal and growth factor responses to heavy
resistance exercise protocols. J. Appl. Physiol. 69: 1442–1450,
1990.
31. Kraemer, W. J., B. Noble, B. Culver, and R. V. Lewis.
Changes in plasma proenkephalin peptide F and catecholamine
levels during graded exercise in men. Proc. Natl. Acad. Sci. USA
82: 6349–6351, 1985.
32. Kraemer, W. J., J. F. Patton, H. G. Knuttgen, C. J. Hannan,
T. Kettler, S. E. Gordon, J. E. Dziados, A. C. Fry, P. N.
Frykman, and E. A. Harman. Effects of high-intensity cycle
exercise on sympathoadrenal-medullary response patterns. J.
Appl. Physiol. 70: 8–14, 1991.
33. Kuipers, H., and H. A. Keizer. Overtraining in elite athletes,
review and directions for the future. Sports Med. 6: 79–92, 1988.
34. Lehmann, M., H. Dickhuth, G. Gendrisch, W. Lazar, M.
Thum, R. Kaminski, J. F. Aramendi, E. Peterke, W. Wieland, and J. Keul. Training-overtraining. A prospective, experimental study with experienced middle- and long-distance runners. Int. J. Sports Med. 12: 444–452, 1991.
35. Lett, E., S. Gangloff, M. Zimmermann, D. Wachsmann, and
J.-P. Klein. Immunogenicity of polysaccharides conjugated to
peptides containing T- and B-cell epitopes. Infect. Immun. 62:
785–792, 1994.
36. Livett, A. R., D. M. Dean, L. G. Whelan, S. Undenfriend, and
J. Rossier. Co-release of enkephalin and catecholamines from
cultured adrenal chromaffin cells. Nature 289: 317–319, 1981.
37. Phillips, J. H. Chromaffin granule biogenesis and the exocytosis/
endocytosis cycle. In: Stimulus-Secretion Coupling in Chromaffin
Cells, edited by K. Rosenheck and P. I. Lelkes. Boca Raton, FL:
CRC Press, 1987, vol. I, p. 32–49.
38. Schwab, R., G. O. Johnson, T. J. Housh, J. E. Kinder, and
J. P. Weir. Acute effects of different intensities of weight lifting
on serum testosterone. Med. Sci. Sports Exerc. 25: 1381–1385,
1994.
39. Urhausen, A., H. H. W. Gabriel, and W. Kindermann. Impaired pituitary hormonal response to exhaustive exercise in
overtrained endurance athletes. Med. Sci. Sports Exerc. 30:
407–414, 1998.
40. Vlahos, C. J., and W. F. Matter. Signal transduction in
neutrophil activation phosphatidylinositol 3-kinase is stimulated without tyrosine phosphorylation. FEBS Lett. 309: 242–
248, 1992.
Downloaded from http://jap.physiology.org/ by 10.220.33.6 on June 17, 2017
8.
steroid hormones and their response during physical exercise.
Int. J. Sports Med. 7, Suppl.: 27–28, 1986.
Alén, M., A. Pakarinen, K. Häkkinen, and P. V. Komi.
Responses of serum androgenic-anabolic and catabolic hormones
to prolonged strength training. Int. J. Sports Med. 9: 229–233,
1988.
Barron, J. L., T. D. Noakes, W. Levy, C. Smith, and R. P.
Millar. Hypothalamic dysfunction in overtrained athletes. J.
Clin. Endocrinol. Metab. 60: 803–806, 1985.
Brandenberger, G., and M. Follenius. Influence of timing and
intensity of muscular exercise on temporal patterns of plasma
cortisol levels. J. Clin. Endocrinol. Metab. 40: 845–849, 1974.
Busso, T., K. Häkkinen, A. Pakarinen, H. Kauhanen, P. V.
Komi, and J. R. Lacour. Hormonal adaptations and modeled
responses in elite weightlifters during 6 weeks of training. Eur. J.
Appl. Physiol. 64: 381–386, 1992.
Dill, D. B., and D. L. Costill. Calculation of percentage changes
in volume of blood, plasma, and red cells in dehydration. J. Appl.
Physiol. 37: 247–248, 1974.
Fahrner, C. L., and A. C. Hackney. Effects of endurance
exercise on free testosterone concentration and the binding
affinity of sex hormone binding globulin (SHBG). Int. J. Sports
Med. 19: 12–15, 1998.
Farrell, P. A. Adrenocorticotropic hormone and exercise. In:
Exercise Endocrinology, edited by K. Fotherby and S. B. Pal. New
York: de Gruyter, 1985, p. 139–156.
Fry, A. C., T. A. Aro, J. A. Bauer, and W. J. Kraemer. A
kinematic comparison of three barbell squat variations and a
squat simulating machine (Abstract). J. Appl. Sport Sci. Res. 5:
162, 1991.
Fry, A. C., W. J. Kraemer, M. H. Stone, B. J. Warren, S. J.
Fleck, J. T. Kearney, and S. E. Gordon. Endocrine responses
to over-reaching before and after one year of weightlifting
training. Can. J. Appl. Physiol. 19: 400–410, 1994.
Fry, A. C., W. J. Kraemer, M. H. Stone, B. Warren, J. T.
Kearney, S. J. Fleck, and C. A. Weseman. The effect of amino
acid supplementation on testosterone, cortisol, and growth hormone responses to one week of intensive weightlifting. Int. J.
Sport Nutr. 3: 306–322, 1992.
Fry, A. C., W. J. Kraemer, F. van Borselen, J. M. Lynch, J. L.
Marsit, E. P. Roy, N. T. Triplett, and H. G. Knuttgen.
Performance decrements with high intensity resistance exercise
overtraining. Med. Sci. Exerc. Sports 26: 1165–1173, 1994.
Fry, A. C., W. J. Kraemer, F. van Borselen, J. M. Lynch, N. T.
Triplett, L. P. Koziris, and S. J. Fleck. Catecholamine responses to short-term, high-intensity resistance exercise overtraining. J. Appl. Physiol. 77: 941–946, 1994.
Fry, R. W., A. R. Morton, and D. Keast. Overtraining in
athletes, an update. Sports Med. 12: 32–65, 1991.
Häkkinen, K., K. L. Keskinen, M. Alén, P. V. Komi, and H.
Kauhanen. Serum hormone concentrations during prolonged
training in elite endurance-trained and strength-trained athletes. Eur. J. Appl. Physiol. 59: 233–238, 1989.
Häkkinen, K., and A. Pakarinen. Serum hormones in male
strength athletes during intensive short-term strength training.
Eur. J. Appl. Physiol. 63: 194–199, 1991.
Häkkinen, K., and A. Pakarinen. Acute hormonal responses
to two different fatiguing heavy-resistance protocols in male
athletes. J. Appl. Physiol. 74: 882–887, 1993.
Häkkinen, K., A. Pakarinen, M. Alén, H. Kauhanen, and
P. V. Komi. Relationships between training volume, physical
performance capacity, and serum hormone concentrations during
prolonged training in elite weightlifters. Int. J. Sports Med. 8,
Suppl.: 61–65, 1987.
Häkkinen, K., A. Pakarinen, M. Alén, H. Kauhanen, and
P. V. Komi. Daily hormonal and neuromuscular responses to
intensive strength training in 1 week. Int. J. Sports Med. 9:
422–428, 1988.
Häkkinen, K., A. Pakarinen, M. Alén, H. Kauhanen, and
P. V. Komi. Neuromuscular and hormonal adaptations in athletes to strength training in two years. J. Appl. Physiol. 65:
2406–2412, 1988.
Hiddinga, H. J., D. D. Isaak, and R. V. Lewis. Enkephalincontaining peptides processed from the proenkephalin significantly enhances the antibody-forming cell response to antigens.
J. Immun. 152: 3748–3759, 1994.
2359