| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of 1 Endocrinology
and 2 Respiratory Medicine, We wished to determine whether the increased ACTH during
prolonged exercise was associated with changes in peripheral
corticotropin-releasing hormone (CRH) and/or arginine
vasopressin (AVP). Six male triathletes were studied during exercise: 1 h at 70% maximal oxygen consumption, followed by progressively
increasing work rates until exhaustion. Data obtained during the
exercise session were compared with a nonexercise control session.
Venous blood was sampled over a 2-h period for cortisol, ACTH, CRH,
AVP, renin, glucose, and plasma osmolality. There were significant
increases by ANOVA on log-transformed data in plasma cortisol
(P = 0.002), ACTH
(P < 0.001), CRH
(P < 0.001), and AVP
(P < 0.03) during exercise compared
with the control day. A variable increase in AVP was observed after the period of high-intensity exercise. Plasma osmolality rose with exercise
(P < 0.001) and was related to
plasma AVP during submaximal exercise
(P < 0.03) but not with the
inclusion of data that followed the high-intensity exercise. This
indicated an additional stimulus to the secretion of AVP. The mechanism
by which ACTH secretion occurs during exercise involves both CRH and
AVP. We hypothesize that high-intensity exercise favors AVP release and
that prolonged duration favors CRH release.
cortisol; osmolality; glucose; renin; adrenocorticotropic hormone; corticotropin-releasing hormone; arginine vasopressin
THE RESPONSE of the hypothalamic-pituitary-adrenal
(HPA) axis to acute exercise has been extensively studied. Exercise to >60% of maximal O2 consumption
( In attempting to examine the mechanism of the ACTH stimulation during
acute exercise in humans, some investigators have measured peripheral
plasma levels of the major ACTH secretagogues corticotropin releasing
hormone (CRH) and arginine vasopressin (AVP) (22, 37). A previous study
from this department showed no increase in peripheral CRH levels in
response to 15 min of high-intensity exercise (90%
During prolonged exercise of lesser intensity, changes in the HPA axis
also occur (16). To our knowledge, only two previous human studies have
measured plasma CRH in protocols in which exercise was maintained for 1 h or more (14, 34). After exercise at 50%
By using an original protocol that combined prolonged submaximal
exercise followed by high-intensity exercise, the present study was
designed to determine whether the expected increases in ACTH and
cortisol during exercise were associated with changes in peripheral CRH
and/or AVP and to examine glucose levels, plasma osmolality,
and volume status as possible contributing factors in mediating the
response. Endurance athletes, such as triathletes, duathletes, and marathon runners, repeatedly exercise for
prolonged periods of time to train for their events. Athletes were
selected as subjects because of the physically demanding nature of the exercise protocol and because of the relevance of the basal ACTH hypersecretion previously documented (17, 22).
Subjects
ABSTRACT
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
INTRODUCTION
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
O2 max)
results in ACTH and cortisol release in proportion to the exercise
intensity (16). Highly trained athletes show a similar degree of
stimulation of the HPA axis at the same relative exercise intensity
(%O2 max), although in absolute terms they require a greater workload compared with untrained individuals (22).
O2 max),
whereas ACTH and AVP rose synchronously (37). This confirmed the
results of Luger et al. (22), who also failed to detect
a rise in peripheral CRH, although the assay they employed lacked
sensitivity. In the exercising horse, synchronous pulses of AVP and
ACTH are noted, without change in CRH levels, as measured in pituitary
venous effluent (3). There is considerable variability in the observed
increase in cortisol, ACTH, and AVP induced by acute exercise; this
variability relates to the suppressibility of this
response by dexamethasone (28, 29). Subjects with a greater AVP
response to intense exercise do not have complete ACTH suppressibility
when exercise is preceded by a 4-mg dose of dexamethasone (28, 29).
These observations support the concept that, during short-duration,
high-intensity exercise, AVP may become the more important ACTH
secretagogue, potentiating CRH-induced ACTH secretion. The data in
studies of horses add weight to the studies of humans; the latter have
the limitation of peripheral plasma measurements.
O2 max until
exhaustion, an increase in CRH, ACTH, and cortisol was seen that was
associated with a fall in plasma glucose to <3.3 mmol/l (34). No
activation of the HPA axis was seen when glucose was kept constant by
using an intravenous glucose infusion during the exercise (34). In a
further study, in which plasma CRH, 
-endorphin, and
cortisol were measured after a 1-h run, CRH was clearly elevated
compared with a control day (14).
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
Exercise Protocol
O2 max test.
O2 max was assessed
for each athlete during his initial visit to the laboratory. A standard
testing protocol, using a cycle ergometer (see
Equipment), was employed for all
athletes. After a 4-min warm-up period was performed at 150 W, the
workload was increased to 250 W for 4 min and then by 50-W increments
at 4-min intervals until exhaustion. The workload changes were achieved automatically under the software control of the Sensormedics 2900 metabolic cart.
Study day exercise test.
After the O2 max
test, each athlete attended the laboratory on two separate occasions
for an exercise day and a nonexercise control day. Training was
forbidden on the mornings before testing took place. The athletes were
required to eat a standard diet, with breakfast at 0700. Fluid intake
was controlled (500 ml water with breakfast along with 250 ml orange
juice, and a further 200 ml of water at 0930). The athlete reported to
the laboratory at 1000. To facilitate venous blood sampling during
exercise, a 13-gauge antecubital fossa long line was inserted with the
use of local anesthesia; after the insertion, the athlete rested
quietly.
30 min). A 10-min warm-up
at 150 W commenced at 1050. Beginning at 1100, each athlete was
required to exercise for 60 min at 70%
O2 max, as
calculated from his O2 max test.
O2 was measured at time
(t) = 5, 10, 15, 30, and 60 min, and
the power output was titrated to maintain the O2 max at 70 ± 3% O2 max. At 60 min, the power output was increased by 25 W every 2 min until the
athlete was exhausted. The athletes were instructed to maintain a
constant speed of ~80 rpm throughout the exercise period. Recovery
was at 150 W for as long as the athlete required. Additional venous
blood samples were collected at t = 0, 30, 60, 75, and 90 min. Sampling was carried out while athletes were in
a seated posture, either at rest or during the exercise on the cycle
ergometer. Over the 90-min exercise and/or sampling period,
each athlete ingested 200 ml water every 20 min (total 900 ml over the
90 min). A final urine sample was collected at
t = 90 min. Dry body mass (with the
subject wearing only cycle shorts) was measured before and after
exercise, and sweat volume was calculated as follows: (loss in body
mass + mass of fluid ingested) (respiratory water loss + urine
volume).
|
Equipment
Breath-by-breath data for expiratory flow, O2, and CO2 were monitored by using a SensorMedics 2900 metabolic cart. Heart rate was monitored by using a Marquette Max-1 electrocardiogram stress system, with the heart rate signal interfaced into the metabolic cart. All exercise tests were performed on a SensorMedics 800 Ergometer that had been modified to fit a competitive cyclist's seat, and each athlete used his own pedals. Expiratory volume was obtained by integration of the flow signal.All parameters were calibrated before each testing session. The flow calibration was verified by using a SensorMedics 3-liter calibration syringe. A two-point calibration of O2 and CO2 was achieved by using two Beta standard gas mixtures: 26 ± 0.02% O2-balance N2, and 16 ± 0.02% O2-4.1% CO2- balance N2. Ambient conditions for room temperature, barometric pressure, and relative humidity were entered into the metabolic cart before each calibration and exercise test, and data were recorded after each exercise test. Results were calculated after averaging data over a 30-s interval.
Assays
Cortisol was measured by ELISA (20). ACTH was measured by immunoradiometric assay (Nicols Institute). The assay coefficients of variation are 3.0% (intra-assay) and 7.8% (interassay), and the sensitivity is 0.7 pmol/l. CRH was measured by radioimmunoassay in methanol extracts of plasma samples (1 ml), as previously described (9). The antiserum (Y2B0) was a gift from Professor P. J. Lowry, Department of Physiology and Biochemistry, University of Reading, UK. Assay coefficients of variation are 10% (intra-assay) and 11% (interassay) at 3.5 pmol CRH/l, and the detection limit (at 95% confidence level) is 0.2 pmol/l. AVP was measured by radioimmunoassay with the use of acetonitrile extracts of plasma (2:1, vol/vol), 125I-labeled AVP purified by using HPLC in a NH4HCO3 buffer eluted with a gradient of 12-48% 2-propanol at 1%/min, and a previously validated antiserum (17). The coefficients of variation are 9.7% (intra-assay) and 10.8% (interassay) at 4 pmol AVP/l, and the detection limit (at 95% confidence level) is 0.3 pmol/l. Plasma renin activity was measured by a trapping assay (26). Other biochemical parameters measured were plasma and urine osmolality and plasma glucose.Statistical Analysis
Hormone and metabolic data were log transformed to stabilize the variance before analysis by using two-way repeated-measures ANOVA, with study condition (exercise vs. control) being the between factor and with time being the within factor. Log-transformed hormonal and biochemical measures were examined for overall changes between30 and 90 min. This range
included baseline, exercise at submaximal and maximal intensities, and
recovery. Where significant changes were observed with ANOVA,
Bonferroni post hoc analysis was used to detect differences from
baseline values (t = 30 min) and control time-matched data as appropriate. General
linear models were used to test the associations between plasma
osmolality and AVP within subjects by using the data from all subjects.
This analysis was further refined to determine whether this
relationship was altered by the performance of high-intensity exercise.
Descriptive results are expressed as means ± SE, whereas hormonal
and biochemical parameters are expressed as geometric means ± SE as
indicated.
| |
RESULTS |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
These athletes were extremely fit, as demonstrated by
mean O2 max of 69.0 ± 0.7 ml · kg
1 · min1.
Between 0 and 60 min, the mean intensity of exercise was maintained between 69 and 72%
O2 max, and it rose to
96.1 ± 2.2% O2 max during the final period of increasing exercise intensity. During the
exercise session, the mean sweat volume was 1,670 ± 97 ml while the
body mass of the athletes fell from 74.3 ± 1.2 to 73.2 ± 1.1 kg
(P < 0.001).
Figure 2 outlines the levels of cortisol,
ACTH, CRH, and AVP during the 90-min study period on the exercise and
control days. Log-transformed levels of each of these hormones were not
significantly different at baseline on the two occasions. Between the
two study conditions, exercise vs. control, there was a significantly
different time course of hormone response (time × study
condition interaction) for log cortisol
(F = 5.34, P = 0.002), log ACTH
(F = 19.59, P < 0.001), log CRH
(F = 20.91, P < 0.001), and log AVP
(F = 3.09, P < 0.03) over the 2-h period
between 30 and 90 min. These data indicate a significant rise in
each of these hormones during the exercise protocol. Further post hoc
analysis was undertaken by using the Bonferroni
t-test as described in the
MATERIALS AND METHODS. Plasma ACTH was
significantly different from baseline (P < 0.01) and time-matched control
data (P < 0.001) by
t = 30 min and showed a large peak at
t = 75 min. Cortisol, which had also
begun to rise by t = 30 min
(P < 0.01 compared with time-matched control), became significantly different from baseline by
t = 60 min
(P < 0.01) and continued to increase
up to t = 90 min. Plasma CRH was
significantly elevated at the 60-min time point and beyond, both
compared with baseline and with control data (P < 0.001 for each). Plasma AVP was
significantly different from baseline
(P < 0.05) and time-matched control
data (P < 0.01) only at
t = 75 min, after the period of
high-intensity exercise.
|
Plasma glucose (Fig. 3A) was similar at baseline under the two study conditions. During exercise, glucose levels fell between 0 and 60 min and subsequently rose between 60 and 75 min, whereas no significant changes occurred over the equivalent times on the control day. Across all time points, ANOVA on the log-transformed data revealed a significant time × study condition interaction (F = 5.23, P = 0.002). The Bonferroni t-test revealed a significantly lower glucose at t = 60 min (4.3 ± 0.35 vs. 4.9 ± 0.1 mmol/l; P < 0.01). Although no subject became frankly hypoglycemic, one developed a level of 3.3 mmol/l at 60 min, whereas the other athletes maintained levels greater than or equal to 3.5 mmol/l throughout. Plasma renin activity (Fig. 3B) was not significantly different at baseline. There was a significant effect of exercise on log plasma renin activity (F = 17.38, P < 0.001), with the Bonferroni t-test confirming significantly elevated levels at t = 60 and 90 min compared with baseline and time matched control data (P < 0.001). Plasma osmolality (Fig. 3C) was similar at baseline. Changes in log plasma osmolality during exercise were highly significant overall (F = 20.56, P < 0.001). The Bonferroni t-test indicated that there was a significant increase from baseline during exercise between t = 30 and 75 min (P < 0.001), a significant decrease from baseline during the control day from t = 60 to 90 min (P < 0.001), and a significant difference between exercise and control from t = 30 until 90 min (P < 0.001).
|
When data from exercise and control sessions were pooled, there was a
highly significant relationship between plasma osmolality and AVP
(F = 18.92, P < 0.001). After exclusion of the
control data to examine this relationship during exercise,
it was maintained during exercise between 30 and
60 min, i.e., the period of prolonged submaximal exercise
(F = 6.17, P < 0.03). The change in plasma AVP
between 60 and 75 min was variable (range, 0.1-37.9 pmol/l), and,
in three of the subjects, the increase in AVP at 75 min appeared to be
higher than predicted from the change in osmolality. This resulted in a
loss of the relationship between plasma osmolality and AVP during the
entire exercise period when the 75- and 90-min time points were also
considered (F = 3.81, P = 0.063). This may be interpreted as
demonstrating that, during prolonged submaximal exercise, AVP is
related to plasma osmolality, but, during high-intensity exercise, AVP
becomes more dependent on an additional stimulus.
Urine osmolality did not show a significant exercise-induced change
(exercise day:
t = 30 min: 553 ± 137 mosmol/kgH2O; t = 90 min:
499 ± 120 mosmol/kgH2O; control
day: t = 30
min: 727 ± 130 mosmol/kgH2O,
t = 90 min: 402 ± 108 mosmol/kgH2O; ANOVA on log-transformed data, change over
time, F = 3.74, P > 0.1; time × study
condition interaction F = 1.83, P > 0.2).
| |
DISCUSSION |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
The results of this study confirm that prolonged submaximal exercise is stimulatory to ACTH and cortisol secretion. This is associated with significant increases in peripheral CRH, compared with nonexercise conditions with similar fluid intake. Although glucose levels fell slightly during the period of prolonged exercise, the elevation in CRH in this study was not associated with frank hypoglycemia. The observed rise in peripheral CRH is in contrast to the situation in acute, nearly maximal exercise, in which, most studies, show CRH fails to change from baseline (22, 37). There is, however, one study that reported an increase in CRH immediately after a short period of intense exercise, as per the Bruce protocol, but there were no control data (8). Our results are consistent with those of Harte et al. (14), who observed an increase in peripheral CRH after a 1-h run. Although there is considerable debate concerning the relevance of peripheral measurement of CRH, a central source of the rise may be suggested by a positive correlation between CRH and mood enhancement during the exercise (14). Whereas basal CRH, as measured in peripheral blood, is derived largely from extrahypothalamic sources (31), the incremental rise seen during the stress of hypoglycemia is thought to represent hypothalamic secretion (9, 31).
Prolonged exercise being stimulatory to CRH secretion would be consistent with the hypothesis that highly trained athletes have increased levels of hypothalamic CRH (22). Repeated bouts of prolonged exercise, such as occur during their normal training routines, may result in chronic elevation in central CRH levels, leading to the observed increase in basal ACTH (17, 22).
Previous studies from this department have documented increases in peripheral CRH during the stress of abdominal surgery (7) and myocardial infarction (6), but not during ethanol-induced nausea (18) or cardioversion and electroconvulsive therapy (12), where AVP appears to be the predominant mediator of the acute rise in ACTH. It is acknowledged that small increases in CRH at the level of the hypothalamic-hypophysial portal (HHP) system will not give rise to changes in peripheral levels caused by the dilution effect. Nevertheless, studies examining HHP blood or pituitary venous blood in higher mammals, such as sheep (10) and horses (2), have suggested that several forms of acute stress activate ACTH secretion, predominantly via AVP, with CRH having a more permissive role.
Under normal conditions, plasma AVP is closely correlated with plasma
osmolality in a linear fashion, although, when pronounced changes in
osmolality occur, a parabolic model produces a better fit (13). In our
study, during prolonged submaximal exercise, AVP showed a small
increase that just failed to reach statistical significance compared
with baseline at t = 30 min.
The extent of this rise was in keeping with that expected from the
changes that occurred in plasma osmolality. However, where a short
period of maximal exercise was superimposed on the prolonged exercise, a further rise in AVP was noted; in some subjects, this increase appeared to be greater than expected from plasma osmolality changes alone. This rise in AVP was associated with an additional
increase in ACTH and, later, in cortisol, and the increase varied
considerably between subjects.
Recent evidence suggests that subjects may be divided into two groups based on whether their HPA-axis response to high-intensity exercise is completely or incompletely suppressed by 4 mg of dexamethasone (28, 29). The nonsuppressors also have greater exercise-induced secretion of AVP, ACTH, and cortisol after placebo (28, 29). Thus any population will have in it both suppressors and nonsuppressors, which may explain the variability in the hormonal response to exercise, particularly in regard to AVP. With only six subjects, our study lacks the statistical power to differentiate between these groups, and we did not set out to do this. However, it is interesting to note that the variability in AVP response was predominantly seen at the 75-min time point after the period of intense exercise and that, during the submaximal exercise, the increase in AVP was quite consistent between subjects in proportion to the changing plasma osmolality. This observation may imply that the variability in HPA-axis response to intense exercise is largely related to the magnitude of the AVP increment. One might hypothesize, therefore, that the observed difference in HPA-axis response between suppressors and nonsuppressors after intense exercise would not be seen with prolonged submaximal exercise. This deserves future study with a larger group of subjects.
The results during the maximal exercise, with AVP and ACTH increasing
synchronously, are similar to those previously reported for humans (37)
and horses (3). The mechanism of this rise is unclear. Convertino et
al. (4) attributed the exercise-induced rise in AVP to
osmolality changes, and, using second-order correlation, AVP failed to
show a significant relationship between plasma volume or plasma renin
activity. Their study demonstrated a curvilinear response of both
osmolality and AVP to a protocol of graded exercise in which the
subjects developed mean plasma osmolality levels of >300
mosmol/kgH2O. In a further study of plasma AVP during exercise (35), changes in AVP were not correlated with changes in
plasma osmolality or plasma volume over all observations, but changes
in AVP did show a positive correlation with work
intensity. Although increases in plasma catecholamines are known to
occur during exercise (5), human evidence does not support a role for
peripheral catecholamines in promoting ACTH secretion (24). However, it
is possible that activation of central
1-noradrenergic mechanisms, which are known to stimulate ACTH predominantly via AVP
secretion (1, 21), may be involved.
It is not possible in our study to distinguish AVP arising from parvocellular vs. magnocellular sources. However, it is clear from several previous studies, both in the horse (19) and in humans (23, 30), that AVP from a magnocellular source may still stimulate ACTH secretion. Data from rats indicate that neurons derived from the magnocellular region of the paraventricular nucleus pass through the median eminence and release vasopressin, which may act directly on the anterior pituitary (15). In addition, variations in blood flow in the HHP system may also result in the delivery of magnocellular-derived AVP to the anterior pituitary (27).
Exercise may be a form of stress where the intensity and/or
duration has a differential effect on factors that mediate ACTH secretion, either with CRH predominating or with CRH and AVP assuming equal importance during prolonged, submaximal exercise and with AVP
becoming more important during short-term, nearly
maximal exercise. A previous study (32), in which 20 min of
exercise were performed, demonstrated that exercise after 4 h of a 1 µg · kg1 · h1
infusion of ovine CRH induced a similar incremental rise in ACTH in
response to exercise during a saline infusion, despite
elevated baseline cortisol and ACTH levels and saturated corticotrope
CRH receptors. The authors concluded that other factors, most likely AVP, act in concert with CRH to mediate ACTH release during acute exercise (32).
The present study utilized a unique protocol in which highly trained athletes sequentially performed prolonged submaximal exercise and high-intensity exercise. Is it possible that the HPA-axis response to the high-intensity exercise was altered by the preceding period of exercise? Theoretically, one could postulate either an enhancement or an attenuation of the ACTH and cortisol response, depending on whether the dominant factor at the commencement of the period of high-intensity exercise is increased baseline CRH or cortisol. In fact, maximal ACTH and cortisol levels in response to the intense exercise in the present study were similar to those of other studies of acute exercise alone, including a previous study from this department (22, 28, 29, 37).
It is also possible that differences between subjects in the lactate
threshold could influence the extent of the HPA-axis response to
submaximal exercise, because plasma lactate correlates with ACTH and
cortisol secretion at 70%
O2 max and above (22). Endurance training increases the relative exercise intensity that results in the accumulation of blood lactate (25, 33, 36), whereas the
optimal training intensity is at or just above the lactate threshold
(11, 33, 36). Although we did not formally measure lactate as part of
the present exercise protocol, preliminary testing on athletes
indicated that our chosen exercise intensity of 70%
O2 max was likely
to be at or just below the lactate threshold for this group (J. Hellemans, unpublished observations). This is in agreement with an
earlier study that demonstrated that the onset of plasma lactate
accumulation (defined in this study as a change in blood lactate of
>1 mmol/l above baseline) in a group of trained athletes was up to
78.9% O2 max (11). Our data for AVP, ACTH, and cortisol at t = 60 min, the end of the submaximal exercise, show considerably less
variability than at the t = 75 min
time point on completion of the high-intensity exercise. This indicates
that any difference in lactate threshold between the athletes had
relatively little impact on the HPA-axis response variability, compared
with the stimulus brought about by the high-intensity exercise.
In conclusion, prolonged, submaximal exercise is associated with significant rises in peripheral CRH that are not associated with hypoglycemia. The rise in AVP is consistent with the plasma osmolality changes that occur. High-intensity exercise is associated with a further elevation in ACTH, combined with an increase in AVP, which in some subjects is out of proportion to osmolality changes. It is proposed that the mechanism by which activation of the HPA axis occurs during exercise may involve the hypothalamic secretion of both CRH and AVP, with high-intensity exercise favoring AVP release and prolonged-duration exercise favoring CRH release.
| |
ACKNOWLEDGEMENTS |
|---|
The authors thank Dr. C. Drennan, Medical Director of the Respiratory Physiology Laboratory; S. Bothwell, respiratory technician; C. Frampton, biostatistician; the nursing staff of the Endocrine Test Centre for assistance; Dr. J. Lewis from the Steroid Laboratory, Canterbury Health Laboratories for the cortisol assays; and Dr. T. Yandle of Endolab for the renin assays.
| |
FOOTNOTES |
|---|
This study was supported by the Health Research Council of New Zealand and by the Canterbury Medical Research Foundation.
Address for reprint requests: W. J. Inder, Dept. of Endocrinology, Christchurch Hospital, Christchurch, New Zealand.
Received 4 August 1997; accepted in final form 1 May 1998.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
1.
Al-Damluji, S.,
R. Thomas,
A. White,
and
M Besser.
Vasopressin mediates 1-adrenergic stimulation of adrenocorticotropin secretion.
Endocrinology
126:
1989-1995,
1990[Abstract].
2.
Alexander, S. L.,
C. H. G. Irvine,
and
R. A. Donald.
Dynamics of the regulation of the hypothalamo-pituitary-adrenal (HPA) axis determined using a non-surgical method for collecting pituitary venous blood from horses.
Front. Neuroendocrinol.
17:
1-50,
1996[Medline].
3.
Alexander, S. L.,
C. H. G. Irvine,
M. J. Ellis,
and
R. A. Donald.
The effect of acute exercise on the secretion of corticotropin-releasing factor, arginine vasopressin and adrenocorticotropin as measured in pituitary venous blood from the horse.
Endocrinology
128:
65-70,
1991[Abstract].
4.
Convertino, V. A.,
L. C. Keil,
E. M. Bernauer,
and
J. E. Greenleaf.
Plasma volume, osmolality, vasopressin, and renin activity during graded exercise in man.
J. Appl. Physiol.
50:
123-128,
1981
5.
Deuster, P. A.,
G. P. Chrousos,
A. Luger,
J. E. DeBolt,
L. L. Bernier,
U. H. Trostman,
S. B. Kyle,
L. C. Montgomery,
and
D. L. Loriaux.
Hormonal and metabolic responses of untrained, moderately trained, and highly trained men to three exercise intensities.
Metabolism
38:
141-148,
1989[Medline].
6.
Donald, R. A.,
I. G. Crozier,
S. G. Foy,
A. M. Richards,
J. H. Livesey,
M. J. Ellis,
L. Mattioli,
and
H. Ikram.
Plasma corticotrophin releasing hormone, vasopressin ACTH and cortisol responses to acute myocardial infarction.
Clin. Endocrinol.
40:
499-504,
1994[Medline].
7.
Donald, R. A.,
E. G. Perry,
G. A. Wittert,
M. Chapman,
J. H. Livesey,
M. J. Ellis,
T. Yandle,
and
E. A. Espiner.
The plasma ACTH, AVP, CRH and catecholamine responses to conventional and laparoscopic cholecystectomy.
Clin. Endocrinol.
38:
609-615,
1993[Medline].
8.
Elias, A. N.,
A. F. Wilson,
M. R. Pandian,
G. Chune,
A. Utsumi,
R. Kayaleh,
and
S. C. Stone.
Corticotropin releasing hormone and gonadotropin secretion in physically active males after acute exercise.
Eur. J. Appl. Physiol.
62:
171-174,
1991.
9.
Ellis, M. J.,
R. S. Schmidli,
R. A. Donald,
J. H. Livesey,
and
E. A. Espiner.
Plasma corticotrophin releasing factor and vasopressin responses to hypoglycaemia in normal man.
Clin. Endocrinol.
32:
93-100,
1990[Medline].
10.
Engler, D.,
T. Pham,
M. J. Fullerton,
G. Ooi,
J. W. Funder,
and
I. J. Clarke.
Studies of the secretion of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) into the hypophysial-portal circulation of the conscious sheep. I. Effect of an audio-visual stimulus and insulin-induced hypoglycemia.
Neuroendocrinology
49:
367-381,
1989[Medline].
11.
Farrell, P. A.,
J. H. Wilmore,
E. F. Coyle,
J. E. Billings,
and
D. L. Costill.
Plasma lactate accumulation and distance running performance.
Med. Sci. Sports
11:
338-344,
1979[Medline].
12.
Florkowski, C. M.,
I. G. Crozier,
S. Nightingale,
M. J. Evans,
M. J. Ellis,
P. Joyce,
and
R. A. Donald.
Plasma cortisol, PRL, ACTH, AVP and corticotrophin releasing hormone responses to direct current cardioversion and electroconvulsive therapy.
Clin. Endocrinol.
44:
163-168,
1996[Medline].
13.
Hammer, M.,
J. Ladefoged,
and
K. Ølgaard.
Relationship between plasma osmolality and plasma vasopressin in human subjects.
Am. J. Physiol.
238 (Endocrinol. Metab. 1):
E313-E317,
1980
14.
Harte, J. L.,
G. H. Eifert,
and
R. Smith.
The effects of running and meditation on beta-endorphin, corticotropin-releasing hormone and cortisol and on mood.
Biol. Psychol.
40:
251-265,
1995[Medline].
15.
Holmes, M. C.,
F. A. Antoni,
G. Aguilera,
and
K. J. Catt.
Magnocellular axons in passage through the median eminence release vasopressin.
Nature
319:
326-329,
1986[Medline].
16.
Howlett, T. A.
Hormonal responses to exercise and training: a short review.
Clin. Endocrinol.
26:
723-742,
1987[Medline].
17.
Inder, W. J.,
J. Hellemans,
M. J. Ellis,
M. J. Evans,
J. H. Livesey,
and
R. A. Donald.
Elevated basal adrenocorticotropin and evidence for increased central opioid tone in highly trained male athletes.
J. Clin. Endocrinol Metab.
80:
244-248,
1995[Abstract].
18.
Inder, W. J.,
P. R. Joyce,
J. E. Wells,
M. J. Evans,
M. J. Ellis,
L. Mattioli,
and
R. A. Donald.
The acute effects of oral ethanol on the hypothalamic-pituitary-adrenal axis in normal human subjects.
Clin. Endocrinol.
42:
65-71,
1995[Medline].
19.
Irvine, C. H. G.,
S. L. Alexander,
and
R. A. Donald.
Effect of an osmotic stimulus on the secretion of arginine vasopressin and adrenocorticotropin in the horse.
Endocrinology
124:
3102-3108,
1989[Abstract].
20.
Lewis, J. G.,
L. Manley,
J. C. Whitlow,
and
P. A. Elder.
Production of a monoclonal antibody to cortisol: application to a direct enzyme-linked immunosorbent assay of plasma.
Steroids
57:
82-85,
1992[Medline].
21.
Liu, J. P.,
I. J. Clarke,
J. W. Funder,
and
D. Engler.
Studies of the secretion of corticotropin-releasing factor and arginine vasopressin into the hypophysial-portal circulation of the conscious sheep. II. The central noradrenergic and neuropeptide Y pathways cause immediate and prolonged hypothalamic-pituitary-adrenal activation. Potential involvement in the pseudo-Cushing's syndrome of endogenous depression and anorexia nervosa.
J. Clin. Invest.
93:
1439-1450,
1994.
22.
Luger, A.,
P. A. Deuster,
S. B. Kyle,
W. T. Galluci,
L. C. Montgomery,
P. W. Gold,
D. L. Loriaux,
and
G. P. Chrousos.
Acute hypothalamic-pituitary-adrenal responses to the stress of treadmill exercise.
N. Engl. J. Med.
316:
1309-1315,
1987[Abstract].
23.
Milsom, S. R.,
J. V. Conaglen,
R. A. Donald,
E. A. Espiner,
M. G. Nicholls,
and
J. H. Livesey.
Augmentation of the response to CRF in man: relative contributions of endogenous angiotensin and vasopressin.
Clin. Endocrinol.
22:
623-628,
1985[Medline].
24.
Milsom, S. R.,
R. A. Donald,
E. A. Espiner,
M. G. Nicholls,
and
J. H. Livesey.
The effect of peripheral catecholamine concentrations on the pituitary-adrenal response to corticotrophin releasing factor in man.
Clin. Endocrinol.
25:
241-246,
1986[Medline].
25.
Myers, J.,
and
E. Ashley.
Dangerous curves. A perspective on exercise, lactate and the anaerobic threshold.
Chest
111:
787-795,
1997
26.
Nussberger, J.,
T. Fasanella d'Amore,
M. Porschet,
B. Waeber,
D. B. Brunner,
H. R. Brunner,
L. Kler,
A. N. Brown,
and
R. J. Francis.
Repeated administration of the converting enzyme inhibitor cilazapril to normal volunteers.
J. Cardiovasc. Pharmacol.
9:
39-44,
1987[Medline].
27.
Page, R. B.
Directional pituitary blood flow: a microcinephotographic study.
Endocrinology
112:
157-165,
1983[Medline].
28.
Petrides, J. S.,
P. W. Gold,
G. P. Mueller,
A. Singh,
C. Stratkis,
G. P. Chrousos,
and
P. A. Deuster.
Marked differences in functioning of the hypothalamic-pituitary-adrenal axis between groups of men.
J. Appl. Physiol.
82:
1979-1988,
1997
29.
Petrides, J. S.,
G. P. Mueller,
K. T. Kaloeras,
G. P. Chrousos,
P. W. Gold,
and
P. A. Deuster.
Exercise-induced activation of the hypothalamic-pituitary-adrenal axis: marked differences in the sensitivity to glucocorticoid suppression.
J. Clin. Endocrinol. Metab.
79:
377-383,
1994[Abstract].
30.
Rittmaster, R. S.,
G. B. Cutler,
P. W. Gold,
D. D. Brandon,
T. Tomai,
D. L. Loriaux,
and
G. P. Chrousos.
The relationship of saline-induced changes in vasopressin secretion to basal and corticotropin-releasing hormone-stimulated adrenocorticotropin and cortisol secretion in man.
J. Clin. Endocrinol. Metab.
64:
371-376,
1987[Abstract].
31.
Sasaki, A.,
S. Sato,
O. Murakami,
M. Go,
M. Inoue,
Y. Shimizu,
K. Hanew,
N. Andoh,
I. Sato,
N. Sasano,
and
K. Yoshinaga.
Immunoreactive corticotropin-releasing hormone present in human plasma may be derived from hypothalamic and extrahypothalamic sources.
J. Clin. Endocrinol. Metab.
65:
176-182,
1987[Abstract].
32.
Smoak, B.,
P. Deuster,
D. Rabin,
and
G. Chrousos.
Corticotropin-releasing hormone is not the sole factor mediating exercise-induced adrenocorticotropin release in humans.
J. Clin. Endocrinol. Metab.
73:
302-306,
1991[Abstract].
33.
Spurway, N. C.
Aerobic exercise, anaerobic exercise and the lactate threshold.
Br. Med. Bull.
48:
569-591,
1992
34.
Tabata, I.,
F. Ogita,
M. Miyachi,
and
H. Shibayama.
Effect of low blood glucose on plasma CRF, ACTH, and cortisol during prolonged exercise.
J. Appl. Physiol.
71:
1807-1812,
1991
35.
Wade, C. E.,
and
J. R. Claybaugh.
Plasma renin activity, vasopressin concentration, and urinary excretory responses to exercise in men.
J. Appl. Physiol.
49:
930-936,
1980
36.
Weltman, A.,
R. L. Seip,
D. Snead,
J. Y. Weltman,
E. M. Haskvitz,
W. S. Evans,
J. D. Veldhuis,
and
A. D. Rogol.
Exercise training at and above the lactate threshold in previously untrained women.
Int. J. Sports Med.
13:
257-263,
1992[Medline].
37.
Wittert, G. A.,
D. E. Stewart,
M. P. Graves,
M. J. Ellis,
M. J. Evans,
J. E. Wells,
R. A. Donald,
and
E. A. Espiner.
Plasma corticotrophin releasing factor and vasopressin responses to exercise in normal man.
Clin. Endocrinol.
35:
311-317,
1991[Medline].
This article has been cited by other articles:
|
|
 |
|
  A. N. Vgontzas, S. Pejovic, E. Zoumakis, H.-M. Lin, C. M. Bentley, E. O. Bixler, A. Sarrigiannidis, M. Basta, and G. P. Chrousos Hypothalamic-Pituitary-Adrenal Axis Activity in Obese Men with and without Sleep Apnea: Effects of Continuous Positive Airway Pressure Therapy J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4199 - 4207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Bernstein, M. C. Costanza, R. W. James, M. A. Morris, F. Cambien, S. Raoux, and A. Morabia Physical Activity May Modulate Effects of ApoE Genotype on Lipid Profile Arterioscler. Thromb. Vasc. Biol., January 1, 2002; 22(1): 133 - 140. [Abstract] [Full Text]
|
|
|
|
|
|
G. K. Adler Editorial: Exercise and Fatigue--Is Neuroendocrinology an Important Factor? J. Clin. Endocrinol. Metab., June 1, 2000; 85(6): 2167 - 2169. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
P < 0.01, 
P < 0.001.
