Download The hormonal response to exercise

The Hormonal Response to Exercise
Henrik Galbo
Department of Medical Physiology B, The Panum Institute, University of
Copenhagen, 2200 Copenhagen N, Denmark
Introduction . . . .. . . . . ... . . . . . . .
.......................................
Sympathoadrenal Activity During Exercise . . . . . .. ... . . .. . . . . . . . . . . . . . . . . . . . .
The Renin-Angiotensin System. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . .. . ..
Gastroenteropancreatic (GEP) Hormones ............. ....................
A. Insulin. .. .. . . . . . . .. .. .. . ..... ..._..... . .. .. . . .. . . .. . . .. . . ... . .. .. .. .. .. ..
B. Glucagon.. .. . . . . . .. . . . .. . .. . . . . .. . . .. . . . . . .. . .. . .. . . .. . . .._...._...... . ..
C. Somatostatin (SRIF) and Pancreatic Polypeptide (PP) . . . . . . . . . . . . . . . . . . . .
D. Other GEP Hormones.. . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
V. Parathyroid Hormone (PTH). . . . . . . . . . . . . . . . . . .. . . ... . . . . . . . . . .. . . . . . . . . . . . . .
VI. The Pituitary Gland.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
VII . Growth Hormone (GH). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
VIII. Prolactin (PRL) . . . . . . . . . . . . . . . . . . . . . . .. . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Lx. Adrenocorticotropic Hormone (ACTH) and Adrenal Glucocorticoids . .... . ..
X. Endogenous Opioid Peptides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
XI. TSH and Thyroid Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . .. . . . . . .
XII. Pituitary Gonadotropins (LH and FSH) and Gonadal Hormones . . . . . . . . . . . .
XIII. The Postexercise Period. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
XIV. Unifying Scheme for the Control of the Hormal Response to Exercise.. . . . . .
xv. Accuracy of Fuel Mobilization in Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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I. INTRODUCTION
In the present paper, the hormonal (including autonomic neuroendocrine)
changes elicited during exercise are outlined. A unifying hypothesis concerning
the control of the hormonal response to exercise is advanced. The influence of
this response on metabolism is discussed in terms of whether the hormonal
changes are compatible with an accurate adjustment of fuel delivery to the
energy needs of the working muscles. Some areas which are likely to attract
future research attention are pointed out. The present exposition is an updated
review and the reader is referred to References 13, 17, 126, and 127 for a more
extensive quotation of these older studies and a detailed bibliography.
11. SYMPATHOADRENAL ACTIVITY DURING EXERCISE
During exercise an increase in sympathoadrenal activity is the most important autonomic neuroendocrine response. If sympathetic (adrenergic) activity is impeded, exercise capacity is reduced.'I2 The increase in sympathoadrenal
DiabetesMetaboIism Reviews, Vol. 1, No. 4, 385-408 (1986)
CCCO742-4221/86/040385-24$04.00
0 1986 by John Wiley & Sons, Inc.
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EXERCISE ENDOCRINOLOGY
activity is of major importance for the cardiovascular adaptation and thermoregulalion that occurs during exercise. The heart rate and force of contraction are
enhanced, the tone of arterioles in the splanchnic area, kidneys and noncontracting muscles is increased, and the spleen-at least in dogs-brought to contract. In this way cardiac output is enhanced and blood volume and flow
redistributed to skin and working muscle. Stimulation of sweat glands increases
evaporative heat loss. Sympathoadrenal activity also influences water and electrofyte balances by facilitating muscular uptake of potassium, by activating the
renin-angiotensin axis (see below), and by a direct effect on the kidney to decrease and redistribute renal blood flow and to directly enhance tubular sodium
reabsorption. In this way the loss of water and electrolytes caused by sweating
is counterbalanced. The secretion of hormones (see below) and substrate mobilization
are profoundly influenced by adrenergic activity. Adrenergic activity also enhances contractility in skeletal muscle, as it does in heart. Finally, studies with
epinephrine infusion3 and p-receptor blockade4,' suggest that augmented sympathetic activity at the onset of exercise increases the rate of ventilation and
pulmonary gas exchange by enhancing circulatory adjustments and thereby
delivery of CO, from the working muscles to the lungs. A direct effect of sympathetic activity on respiration or airway resistance during exercise6 have not
been found.
In humans, the best practical way to assess sympathoadrenal activity during
exercise is to measure the concentrations in plasma of free norepinephrine and
epinephrine. At rest about 80% of circulating catecholamines are sulfate conjugates. During exercise the concentrations of these decrease for reasons unknown. However, the concentrations of free norepinephrine and epinephrine
have been shown to increase during exercise in humans8, similarly in men and
women, as well as in several other mammalian species, including dog9,"' and
rat"*'2, and primitive vertebrates.
During exercise the main source of plasma norepinephrine is skeletal
rnu~cle~,'~.
However, the relationship between sympathetic nervous activity and
tissue overflow of norepinephrine to the blood stream is obscure and the organ
distribution of electrical impulses within the sympathetic nervous system is
unknown.14 The kinetics of epinephrine in plasma are easier to interpret than
those of norepinephrine. It has been shown that during exercise the increase
in epinephrine concentration closely reflects increased adrenomedullary secretion, since epinephrine clearance varies little.I5 At low work loads clearance
increases slightly (15%),whereas at high workloads it decreases slightly (20%)
and is inversely related to the relative work intensity."
In man, increases in catecholamine concentrations have been found during
static (isometric) as well as during dynamic exercise. Norepinephrine and epinephrine concentrations in plasma vary exponentially with work intensity and
VO, during dynamic exercise. Norepinephrine levels increase significantly at
work loads lower than those that cause an increase in epinephrine levels.'6 At
a certain VO, catecholamine levels are higher during work with small muscle
than during work with large
groups with a low muscle group specific V02max
Furthermore, the rise in plasma epinephmuscle groups with a high V02max.18
rine is larger relative to that of norepinephrine during static than during dynamic e~ercise.'~,'~
Comparison between dynamic and static exercise performed
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with the same muscle group reveals that the increase in plasma norepinephrine
is larger relative to the increase in heart rate during the former type of exercise.”
The duration of exercise also appears to be an important regulator of sympathoadrenal activity. Thus, at a constant VOz, norepinephrine and, more markedly, epinephrine levels in plasma increase continuously up to the time of
exhaustion. 1,15,19
Availability of oxygen and norepinephrine concentration in plasma appear
to be closely associated, but the exact mechanism is not known. Studies performed at rest and during exercise in patients with ischemic heart disease as
well as in healthy subjects have shown that the concentration of norepinephrine
in plasma varies inversely with (is negatively correlated to) the oxygen saturation of mixed venous blood. Furthermore, catecholamine concentrations in plasma
are higher and lower, respectively, when exercise is performed during hypoxia20,21
and hyperoxia, than when it is performed during normoxia. It has been claimed
that the close relationship between plasma norepinephrine concentration and
relative VO, is essentially unaffected by hypoxemia.” However, catecholamine
levels tend to be higher, at comparable relative loads, during hypoxia than
during normoxia” indicating an effect of hypoxemia per se on sympathetic
activity.
A number of factors have been shown to moderate sympathetic nervous
systems activity during exercise. Stimulation of temperature receptors (either
hot or cold) enhances sympathetic activity.22Pressure and volume receptors
also appear to modulate sympathoadrenal activity during exercise. Epinephrine
secretion also is very sensitive to a decrease in plasma glucose concentration
during exercise while stimulation of norepinephrine secretion by hypoglycemia
is less conspicuous.~7~’9~23
In dogs, both infusion of glucose into the carotid
artery or the lateral cerebral ventricle2*and infusion into the portal veinz5reduce
the increase in plasma norepinephrine observed during prolonged exercise,
indicating that cerebral and hepatic glucoreceptors participate in the control of
sympathetic activity during exercise. The responsiveness of these centers may
depend on insulin availability in the time preceding exercise. The evidence
underlying this view is that the catecholamine response to exercise is exaggerated in states of insulin deficiency such as fasting,26 intake of a high fat-low
carbohydrate diet, and poorly controlled diabete~.’~
Furthermore, in diabetic
subjects the catecholamine response to exercise is gradually normalized during
2 weeks of optimum insulin treatment.27Glycogen availability in working muscles does not influence catecholamine levels when the plasma glucose concentration remains constant.
During a period of vigorous endurance training a significant reduction in
catecholamine response to a given absolute work load is seen within one week.
The reduction is more readily apparent for norepinephrine than for epinephrine.28After training, the norepinephrine concentration in plasma is lower than
before whether exercise is carried out with trained or untrained muscles. The
resting norepinephrine concentration in plasma, as well as the vasoconstrictor
activity in sympathetic fibers innervating skeletal muscle, are unaffected by
trainingz9 However, the resting level of epinephrine and the epinephrine response to insulin-induced hypoglycemia is higher in endurance athletes than
in sedentary subject^.*^*^^ Furthermore, in the former subjects plasma epineph-
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EXERCISE ENDOCRINOLOGY
rine concentrations have been found to be higher at identical supramaximal
relative work intensities3' as well as at the end of prolonged exhausting exercise
even though the heart rate was identical to those of untrained subjects. These
findings indicate that the capacity to secrete epinephrine is increased in athletes,
a fact which probably improves exercise capacity.
The increase in norepinephrine levels during isometric exercise has by some,
but not all,32been found to increase with age. Acute administration of drugs
may also influence the catecholamine levels achieved during exercise. Thus,
catecholamine concentrations are increased by a- as well as by P-adrenergic
receptor-blocking agents,3335 by atropine,35by opiate antagonists such as nal ~ x o n eand
, ~ ~by the serotonergic antagonist, k e t a n ~ e r i nOn
. ~ ~the other hand,
during exercise plasma catecholamine concentrations are lower after administration of dopamine agonists and ganglionic blockade. After chronic P-adrenoceptor antagonism enhanced catecholamine responses to exercise are not always
seen.% Destruction of noradrenergic nerve endings with 6-hydroxydopamine
results in lower plasma concentrations of norepinephrine in exercising rats than
is normally
while in exercising dogs a compensatory increase in adrenomedullary secretion may increase the total plasma catecholamine concentration."
The adrenergic response to exercise also is influenced by underlying disease. In diabetics, the catecholamine response to dynamic exercise is increased
if they are poorly controlled, and decreased if they have autonomic neuropathy.40The sympathoadrenal response to exercise may be blunted in asthmatic
subjects, whereas higher norepinephrine concentrations may be found during
exercise in hyperthyroid patients compared to controls. In hypertensive subjects, the norepinephrine concentration has been reported to be higher during
dynamic but lower during isometric exercise than in controls.41Patients with
ischemic heart disease have high plasma norepinephrine levels during exercise
and aerobic training diminishes the catecholamine response to exercise in patients with coronary arterial disease.42
In summary, many factors are known to influence sympathoadrenal activity
during exercise and these have been briefly reviewed. The exact mechanisms
by which they act and their quantitative importance for the sympathoadrenal
response to exercise is in large part, still unknown. Several of the factors mentioned may interact, and their interplay in the regulation of sympathoadrenal
activity during exercise is far from fully explored.
111. THE RENIN-ANGIOTENSIN SYSTEM
During exercise increased sympathoadrenal activity, mainly via P-adrenergic mechanisms, causes secretion of the proteolytic enzyme, renin, into the
circulation. Renin cuts off angiotensin 1 from the circulating globulin called
angiotensinogen or renin substrate. Angiotensin 1 is converted to angiotensin
2, which directly stimulates the adrenal cortex to secrete aldosterone. Angiotensin 2 also acts on the subfornical area in the diencephalon, an area "outside
the blood-brain barrier," to stimulate neural areas involved with thirst and release of antidiuretic hormone (ADH) from the posterior pituitary gland.43Aldosterone and ADH reduce sodium and water losses by their actions on the
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kidney. Thus, the renin-angiotensin system plays an important role in this
maintenance of body fluid homeostasis during acute exercise and may contribute to expansion of the extracellular volume during a period of training.
The plasma concentrations of renin, angiotensin, aldosterone, and ADH
are directly related to intensity and duration of e ~ e r c i s e . ~The
~ , ~hormonal
~,~~,~
responses are determined by the relative, rather than by the absolute work load.
Thus, the state of physical conditioning also influences the hormonal response
with the concentrations of renin, aldosterone, and ADH43in plasma being lower
during exercise in trained than in untrained subjects. In accordance with the
known stimulatory effect. of the sympathetic nervous system on the reninangiotensin system, serotonergic and opioid blockade have been shown to enhance the responses to exercise of renin and a n g i o t e n ~ i nand
~ ~a l d ~ s t e r o n in
e~~
parallel to the magnitude of the catecholamine responses. The concentrations
in plasma of angiotensinogen and converting enzyme probably do not change
during e ~ e r c i s e . ~ ~ , ~ ~
Baroreceptors, especially low pressure receptors that sense reductions in
extracellular fluid volume, are involved in stimulation of the renin-angiotensin
system during exercise. Thus, the exercise-induced increase in renin concentration is enhanced after sodium restriction and inhibited after a high sodium
intake. During prolonged exercise increases in renin and aldosterone are lower
when electrolyte solutions rather than when water are administered. During
exercise in a hot environment an exaggerated decrease in plasma volume is
seen, and this is accompanied by an enhanced renin response. Also, at similar
decreases in plasma volume, stimulation of low pressure receptors in the central
circulation is probably more intense during upright than during supine exercise
and the increase in plasma concentration of ADH is more pronounced under
the former compared to the latter conditions. Changes in plasma osmolality are
highly correlated with changes in plasma ADH during graded exercise43but it
is clear that changes in osmolality and blood pressures cannot fully explain the
exercise-induced changes in renin and ADH
The increase in aldosterone concentration in plasma during exercise is not
entirely due to increased renin levels. Increases in plasma potassium and ACTH
concentrations, as well as a decrease in the clearance of aldosterone contribute
to the higher aldosterone levels.
IV. GASTROENTEROPANCREATIC (GEP) HORMONES
A. Insulin
The most important effect of sympathoadrenal activity on hormone secretion in exercise is an w-adrenergic inhibition of insulin release.35Although insulin clearance has been shown to decrease,47,the plasma insulin concentration,
like that of C peptide, predictably decreases when the intensity of exercise
exceeds approximately 40-50% of V 0 2max . In man, the a-adrenergic inhibition
of insulin release during exercise is exerted by sympathetic nerves to the pancreas, while in sheep and rat48epinephrine contributes to the @-cellinhibition.
In accordance with sympathetic inhibition of insulin secretion, it has been shown
that during exercise of more than mild intensity, insulin secretion is rather
insensitive to changes in plasma glucose c ~ n c e n t r a t i o n . ~ ~
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EXERCISE ENDOCRINOLOGY
The concentrations of insulin and C peptide in plasma decrease with the
and the decrease is less pronounced in trained than in
duration of
untrained subjects. In obese subjects and in normal subjects ingesting a carbohydrate enriched diet, insulin and C-peptide levels are higher than normal
in the postabsorptive state as well as during exercise. Conversely, both at rest
and during exercise insulin levels are lower after fastingZband fat diet.23Insulin
levels are of course low both at rest and during exercise in insulin-deficient
diabetics. It is now well established that exercise may enhance the absorption
of insulin from subcutaneom depots in normal and diabetic individuals.
In the postexercise period insulin concentrations are low relative to the
plasma glucose concentration during oral glucose loading in man.49,50
This may
be due to diminished glucose-induced secretion of gastric inhibitory polypeptide
(GIP), an insulin s e c r e t ~ g o g u eor
,~~
to persistently high alpha-adrenergic tone.
In sedentary rats a reduction in the sensitivity of insulin secretion to glucose
per se has been demonstrated”’ and contributed to the lower plasma insulin
concentrations after an intravenous glucose bolus. Following physical training
the reduction in glucose-induced insulin secretion has been shown to be more
pronounced when glucose is administered orally than intraven~usly.~’
Importantly, the diminished plasma insulin and C-peptide responses to oral glucose
were associated with a decreased GIP response,53again suggesting that exercise
may influence the enteropancreatic axis. In man an effect of physical training
to reduce the plasma insulin response to oral glucose can be demonstrated 4
days after the last training session,53 indicating that the reduction in insulin
secretion represents a long-term adaptive response to physical conditioning. In
rats exercise training also has been shown to diminish the insulin response to
intravenous glucose, tolbutamide, and arginine loads54and the effect persists
well after the last bout of e~ercise.~’
A decreased intrinsic sensitivity of the P cells to stimulation by glucose has
been demonstrated. Thus, the ability of glucose to stimulate insulin secretion
by cultured islets isolated from trained rats has been shown to be reduced.55
These data demonstrate that training-induced hypoinsulinemia observed in vivo
is not solely dependent upon alterations in the hormonal or metabolic milieu
or in neurogenic stimulation of the islets, but also reflects long-term adaptations
within the pancreatic (3 cells. These long-term changes in insulin secretion cannot be explained by altered glucose utilization by the islets.56Since the sensitivity of the P cells to stimulation is directly related to the preceding plasma
glucose level,57it is possible that a lower average glucose level in physically
active compared to sedentary individuals contributes to development of the
P-cell adaptations. Additional factors which may contribute to the diminution
in insulin secretion are the high catecholamine levels in exercising individuals.
The mechanisms involved in development of training induced adaptations in
pancreatic islets (and in other endocrine organs, e.g., the adrenal medulla), as
well as characterization on the molecular level of these adaptations, are important areas for future research.
Short lived effects of a single bout of exercise on sensitivity to stimulation
of endocrine glands have to be separated from more permanent changes induced by regularly repeated exercise (physical training). Whole body insulin
sensitivity is increased in trained subjects5$ as well as after a single bout of
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exercise in untrained subjects.59The effect of acute exercise can at least partly
be ascribed to an increase in glucose transport in skeletal muscle60 and increased
transport has also been found in trained muscle in v i v ~Acute
. ~ ~ exercise does
not influence glucose transport in fat cells, whereas glucose transport is increased by physical t r a i n i r ~ g . ~The
' , ~ ~latter effect has been shown to be due to
an increase in the number of insulin-displaceable glucose transporters after
training.62Insulin binding to muscle has been reported to be either unchanged63
or slightly increased after acute excise and similar findings have been reported
concerning insulin binding to muscleMand fat61cells after training. These findings confirm the general impression65 that changes in insulin receptor status
cannot explain the improvement in insulin-mediated glucose uptake following
acute exercise or physical training. The topic of exercise and insulin sensitivity
is discussed at length in the chapter by Koivisto and associates in this issue.
Important aims for future research are to clarify the exact stimuli responsible
for exercise-induced adaptations in hormone-sensitive target cells and to describe in molecular terms the basis for these adaptations.
8. Glucagon
In man, a decrease in plasma glucagon concentration is found during brief
exercise.',26If exercise is prolonged, the glucagon concentration subsequently
increases but does not exceed basal levels until more than one hour of mild to
moderate intensity exercise.1,66However, in rats and sheep the glucagon concentration increases early in exercise. In these species stimulation of glucagon
secretion by epinephrine explains, in part, the re~ponse.~'
In rats, as well as in
dogs, autonomic nerves also are involved. In man, however, the autonomic
nervous system (including the adrenal medulla) is not of major importance for
the exercise-induced increase in plasma glucagon concentration.1,16,35 It w ould
appear that decreased glucose availability stimulates the glucagon-secreting cells
during prolonged exercise in man.23,34Studies comparing the effect of exercise
and insulin-induced hypoglycemia indicate that the sensitivity of the glucagonsecreting cells to a decrease in plasma glucose concentration is increased during
exercise.l 7 r 3 O Factors, which might contribute to an increase in sensitivity during
exercise include decreased pancreatic blood flow, diminished tissue concentration of insulin, and increased plasma concentrations of GH, cortisol, gastrin,
and VIP. A protracted decrease in glucose availability may also induce a resetting of the stimulus-secretion coupling during prolonged exercise.57
Insulin availability over the period preceding exercise may influence glucagon concentrations during exercise. Thus, glucagon levels are higher in states
of insulin deficiency such as fasting,26high fat-low carbohydrate diet, and poorly
controlled diabetes. Insulin availability is plentiful in obesity. Unfortunately,
the available studies comparing glucagon responses to exercise in obese and
normal weight subjects are inconclusive since the two groups were not matched
for age, sex, and exercise intensity.67Physical training diminishes the increase
in glucagon concentrations seen in response to a given absolute or relative work
load.68The change in response is detectable within a few weeks of vigorous
endurance training.
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392
C. Somatostatin (SRIF) and Pancreatic Polypeptide (PP)
The concentrations of SRIF and PP in peripheral plasma increase gradually
during prolonged mild exercise.47The exercise-induced increases are inhibited
by p-adrenergic antogonists and enhanced by a-adrenergic blockade. The increase in SRIF is seen earlier in diabetics than in controls. The PP concentration
increases with exercise intensity, and the response to exercise is diminished by
autonomic neuropathy and physical training. In addition to P-adrenergic activity, vagal activity stimulates PP secretion. The PP response to insulin-induced
hypoglycemia is higher in trained compared to untrained s~bjects,~'
and this
may reflect a higher vagal activity in the former group.
D. Other GEP Hormones
The concentrations in peripheral plasma of vasoactive intestinal polypeptide (VIP), peptide histidine isosoleucine amid (PHI), secretin, substance P, and
gastrin all have been shown to increase during prolonged e ~ e r c i s e . ~The
~,~~,~~
responses of VIP, PHI, and secretin, but not substance P, are inhibited when
oral glucose is administered during exercise.69Training does not influence these
response^.^^ During brief maximum exercise no changes have been found in the
plasma VIP concentrationz6. Similarly, during prolonged exercise levels of neuand
rotensin and bombesin (GRP),69 gastric inhibitory polypeptide (GIP),47,66
gut glucagon have been shown to be unchanged.
For most of the GEP hormones (with the obvious exceptions of insulin and
glucagon), we do not know their origin during exercise nor do we know the
stimuli regulating their release nor do we understand their role, if any, in metabolic responses to exercise. Interestingly, VIP and PHI are probably cosecreted
from peptidergic nerves. Similarly, peptides may be cosecreted with traditional
hormones and neurotransmitters, such as enkephalins with epinephrine, and
The possible importance of such coseneuropeptide Y with n~repinephrine.~'
cretion has not been taken into account in previous inhibitionheplacement experiments designed to elucidate the role of these hormones in e ~ e r c i s e .Future
'~
studies must take such cosecretion into account, since important interactions
are likely to exist between cosecreted hormone^.^'
V. PARATHYROID HORMONE (PTH)
A small increase in the plasma concentration of PTH has been found during
exercise in man7*and in animals. The increase cannot be explained by changes
in the ionized calcium concentration, but may be related to increased P-adrenergic activity. Not all studies have shown an increase in PTH levels during
exercise in man.72 However, it has been proposed that during exercise an adrenergic enhancement of PTH secretion is counteracted by an increase in ionized
calcium that results from metabolic acidosis."
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VI. THE PITUITARY GLAND
In response to exercise ADH is released (see preceding discussion), whereas
the evidence for an increase in the levels of the other posterior pituitary hormone, oxytocin, is weak. Several anterior pituitary hormones are released during exercise:
VII. GROWTH HORMONE (GH)
GH hormone concentrations in plasma increase during exercise, reflecting
an increase in secretion rate. The increase is seen within a few minutes after
the onset of work and the delay is inversely related to work intensity. Increased
GH release may be found after 30-60 min of exercise at a work load equivalent
to only 10-15% of VO, max. Plasma concentrations of GH increase progressively
with time during exercise of constant intensity.”~~~
GH secretion increases with
increasing work load. Studies comparing continuous and intermittent exercise75
or work with differentload and frequency of movements74have shown that the
GH response is more closely related to the peak intensity of exercise than to
the total work output. Furthermore, the GH response is higher during arm than
during leg exercise.76
The GH response to exercise may have some peculiar features. Some authors have described lower concentrations in plasma during maximal than during submaximal exercise, and the GH response may wane with time during
prolonged or intermittent exercise. Furthermore, individual changes in plasma
GH concentrations during exercise sometimes have a rather irregular time course.
These findings may, to some extent, be explained by the fact that GH secretion
is pulsatile and is subjected to negative feed back inhibition from circulating GH
Illustrating the complex nature of the neuroendocrine control of GH secretion, the GH response to exercise can be inhibited by administration of SRIF,
a-adrenergic receptor-blocking agents, serotoninergic receptor-blocking agents,
dopaminergic receptor-blocking agents, and by cholinergic receptor-blocking
agents; conversely, GH secretion can be enhanced by p-adrenergic receptorblocking agents. Blockade of opioid receptors with naloxone does not alter the
GH response to exercise.36
During exercise, GH release is enhanced by a decrease in glucose availability, by hypoxia, and by a rise in body t e m p e r a t ~ r e , ~and
- ~ *is inhibited by
free fatty acids. The GH response to exercise is smaller in trained than in untrained subjects when compared at similar relative or absolute work loads. Poor
physical fitness in the elderly and in women is probably, in part, responsible
for the exaggerated GH response to exercise in these groups.
Insulin availability in the time preceding exercise also appears to be of
importance in determining the GH response to exercise. In accordance with this
view, the GH response is exaggerated in hypoinsulinemic states such as fasting,26intake of a high carbohydrate-low fat diet, and in poorly controlled diab e t e ~Conversely,
.~~
the GH response to exercise is reduced in states of peripheral
hyperihsulinemia such as obesity, optimally treated diabetes,27and ingestion of
a high carbohydrate diet. The lack of significant increase in GH concentration
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EXERCISE ENDOCRINOLOGY
in diabetics with autonomic neuropathy during a graded exercise test is probably
not due to impaired peripheral sympathetic activity but possibly to lesions in
neurons that trigger GH relea~e.~'
At variance with the view that GH secretion
during exercise is diminished by autonomic neuropathy, it has been reported
that, in response to 25 min of bicycle exercise, GH concentrations increased
more or to the same extent in diabetics with neuropathy compared to those
without neurologic i n ~ o l v e m e n t . ~ ~
VIII. PROLACTIN (PRL)
In humans of both sexes the concentrations of PRL in plasma increase
progressively during heavy exercise,s0,81The peak concentration may be reached
~~
one
, ~ study
~
PRL levels decreased during 30 min
after the end of e x e r c i ~ e .In
of mild exercise. However, it is known that PRL levels decrease spontaneously
during the morning, making the reported decreases3 difficult to interpret. In
women, exercise increases PRL levels in the follicular as well as in the luteal
phase. Interestingly increased PRL levels have been found in women after a
marathon but not during an intense 3 h water polo training session.80Although
postmarathon levels were in the abnormal range, none of the runners complained of galactorrhea.*' In rats, no significant change in plasma PRL was
found during prolonged running.@
The PRL response to exercise is enhanced when a diet rich in fat and low
in carbohydrate is ingested.85A similar enhancement is observed during a 59 h
fast, by an increase in body temperature,s6 and by blockade of opoidZ6or
P-adrenergic receptor. Conversely, the exercise-induced stimulation of PRL secretion is inhibited by a-adrenergic blockade. Glucose availability during exercise is not an important determinant of the PRL response69and the increase in
plasma PRL during insulin-induced hypoglycemia is similar in trained and untrained subjects.88In men, basal PRL levels are not changed during 20 days of
strenuous running.81However, lower resting PRL levels have been reported in
male distance
Similarly, in female swimmers, resting PRL levels have
been found to be decreased following strenuous compared to moderate intensity
training programsm With submaximal exercise the PRL response has been found
to be slightly lower in trained versus untrained males.69In some contrast to
these findings a small increase in the TRH-stimulated PRL response has been
reported to occur during training. It has been claimed that the PRL response to
running at 80% of VOgmax is lower in amenorrheic compared to eumenorrheic
women.% However, as judged from heart rates and plasma lactate levels, the
relative work load may have been lower in the former than in the latter group.
IX. ADRENOCORTICOTROPIC HORMONE (ACTH)
AND ADRENAL GLUCOCORTICOIDS
The concentration of ACTH in plasma increases with the intensity" and
d ~ r a t i o n of
~ ~exercise.
, ~ ~ During exercise of constant intensity an increase in
ACTH is followed within 10 min by an increase in the secretion rate and plasma
concentration of ~ o r t i s o 1ACTH
. ~ ~as~well
~ ~as~cortisol
~ ~ ~levels
~ ~ may peak after
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the end of e ~ e r c i s e . ~The
~ , ~increase
~ , ~ ~ in plasma ACTH also stimulates the
production of aldosterone, but its effect is less important than the rise in angiotensin levels in response to the hyperreninemia (see preceding discussion).
The lowest work load at which an increase in plasma cortisol level has been
However, this does not mean that low intensity
detected is 25% of VO,,.
exercise (< 25% of VO,),,,
does not stimulate cortisol secretion, because the
clearance of cortisol is increased at low (as well as high) work loads. Thus, a
stimulatory effect of exercise on cortisol secretion could be masked by an increase in the metabolic clearance rate. The relative, rather than the absolute
work load, has been shown to be important for the plasma cortisol response to
exercise and, at any given work intensity, the plasma cortisol level increases
more during hypoxic exercise than under normoxic conditions. When studied
at the same submaximal work loads, trained persons have been found to have
a smaller rise in plasma cortisol than untrained persons. This may partly be due
to a higher cortisol clearance in trained subjects. In one study, training increased
the ACTH response to a given relative work load.91
The plasma cortisol concentration displays an intrinsic circadian periodicity.
During the day the cortisol concentration decreases, but this decrease may be
interrupted by secretory peaks related to meals or provoked by e x e r c i ~ e . ~ ~ , ~ ~ , ~ ~
A meal prior to subsequent exercise diminishes the cortisol response.95 Similarly, prior exercise blunts subsequent meal related peak^.^',^^
During prolonged submaximal exercise in man increases in ACTH and cortisol levels coincide with a decrease in blood glucose concentration below 3.3
mmoUliter .17,96 Physical training delays the time at which this glucose concentration is reached and also delays the increase in ACTH and cortisol levels
(Tabata, personal communication). Furthermore, the infusion of glucose during
prolonged submaximal exercise in man inhibits the rise in plasma ACTH levels.% Shularly in running dogs, SIUF infusion exaggerates the decrease in plasma
glucose and this is associated with an increase in the plasma cortisol level. When
hypoglycemia is prevented with a concomitant glucose infusion,19 the plasma
cortisol response is blocked. These results indicate that the blood glucose level
plays an important modulating role on the cortisol response to exercise. Available evidence indicates that receptors in brain and liver mediate the effect of
the plasma glucose concentration on the glucocorticoid response to exercise,
and that this response is exaggerated in hypoinsulinemic states such as diabetes.
An increase in body temperaturesE as well as psychological stress97also have
been shown to augment the exercise-induced increase in plasma cortisol concentration. The cortisol response to exercise also is enhanced by blockade of
P-adrenergi~~~
or ~ p i o i dreceptors.
~~
The physiological significance of the changes in plasma glucocorticoid concentration during exercise has not been determined. However, it may be proposed that during prolonged exercise an increase in glucocorticoids may enhance
the stimulatory effect of other hormones on glucose production and lipoly~is.'~
Another possibility is that repeated increases in plasma cortisol with each exercise bout are involved in some enzymatic adaptations to training.I7 Interestingly, an increased number of glucocorticoid cytosolic receptors has been found
in hearts from trained rats.
396
EXERCISE ENDOCRINOLOGY
X. ENDOGENOUS OPIOID PEPTIDES
These substances have drawn considerable attention in recent years because
they have properties, including narcotic potency, similar to those of morphine.
p-endorphin is derived from p-lipotropin which, in turn, is derived from the
same precursor molecule as ACTH. The enkephalins are shorter peptides, which
share a region of homology with p-endorphin but are derived from a distinct
precursor. P-endorphin and enkephalins are found in several areas within the
brain and are also found outside the brain, for instance, @-endorphinis cosecreted with ACTH from the anterior pituitary and enkephalins are cosecreted
with catecholamines from the adrenal medulla.
The evidence concerning the response of these hormones to exercise is still
scarce. An increase in @-endorphinlevels have been documented during exercise%
and the plasma concentration is directly related to the intensity98and duration99,'00
of exercise. The response is enhanced by increased body temperature during
exercise.loo A rise in plasma met-enkephalin also has been found in response
to prolonged, high intensity
but not to less demanding exercise.%In
exercising rats the opioid levels in different regions of the brain have been
shown to change to varying extents and in different directions.@
Resting @-endorphinlevels in plasma have been claimed to increase during
periods of strenuous training,89but in other studies, similar values were found
in trained and untrained subjects.98~w~10'
Training has also been reported to
increase plasma p-endorphin levels during exercise of a given relative intensity9*,lm
but this finding has not been observed by others.w The increase in plasma pendorphin during insulin-induced hypoglycemia is similar in trained and untrained subjects.88
Endogenous opioids have been proposed to account for the increase in pain
threshold as well as for the acute reduction in anger, depression, and anxiety
which may result from a single bout of exercise. However, the latter observations have been refuted by others. 102,103 Studies with nalaxone have suggested
that the opioids may be involved in the regulation of hormonal responses to
exercise.36During intense exercise, ventilation tends to be increased by naloxone, whereas other cardiopulmonary variables are not a f f e ~ t e d . ~ ~ , " ~
XI. TSH AND THYROID HORMONES
In spite of much research, the influence of physical exercise on thyroid
function is still obscure. In a number of investigations, including varied work
protocols, including mild to strenuous exercise in both normal and diabetic
subjects, no effect of exercise on the plasma concentration of thyroid-stimulating
hormone (TSH) was found. In contrast, in other studies the TSH concentration
has been found to increase progressively with work 10ad.l'~More recent studies
have attempted to resolve this controversy, but again both increasedlo6 and
decreased36TSH levels have been found in response to exercise.
An exercise-induced increase in TSH levels might be expected to stimulate
the thyroid gland. However, a delay is inherent in the stimulus-secretion coupling and an increase in the concentration in plasma of the thyroid hormone
may not be expected until several hours after the increase in TSH. In accordance
GALBO
397
with this, increased T, levels have been found 90 min after a 60 min bout of
acute exercise'06 and at the end of a 60 km run.81 The evaluation of thyroid
function from measurements of thyroid hormone concentrations in plasma is
complicated for a number of other reasons. First, the extracellular hormone pool
is large, making small changes in plasma hormone concentration difficult to
detect. Second, changes in the hormone clearance during exercise (due to an
increase in the concentration of free hormone resulting from a decrease in binding affinity to circulating proteins or to a tissue adaptation facilitating removal)
could easily obscure away increased secretion of thyroid hormone. Third, exercise-induced changes in thyroid hormone concentrations in plasma may be
entirely due to changes in the concentrations of binding proteins. However, the
literature is clear that the plasma concentrations of the thyroid hormones, T,
and T, (triiodothyronine), and of the inactive T4 metabolite, reverse T, (IT,), are
essentially unchanged by a single bout of exercise.
Controversy also exists concerning the effect of chronic physical training
on circulating thyroid hormone levels. In some studies basallo6TSH levels have
been found to be increased by physical training in man and an increased rate
of T, secretion has been reported in man and horses following physical training
compared to sedentary individuals. However, these findings have not been
confirmed by others, and the T, secretion rate has been shown to be similar in
trained rats and in weight-matched controls. Furthermore, in both groups the
T, secretion rate was lower than in freely eating controls. Similarly, basal and
TRH-stimulated plasma TSH concentrations have been shown to be similar in
trained rats and in weight-matched controls, and in these groups lower than in
freely eating controls. These differences were accompanied by opposite changes
in peripheral tissue sensitivity to thyroid hormones. Available data on basal
metabolic rate and on thyroid hormone-dependent mitochondria1 enzymes in
the liver do not suggest that physical training changes the "thyroid status."
XII. PITUITARY GONADOTROPINS (LH AND FSH) AND
GONADAL HORMONES
In male as well as in female rats the concentration of the luteinizing hormone (LH) in plasma has been found to decrease during running, whereas that
of the follicle stimulating hormone (FSH) does not ~ h a n g e . ~LH
, ' ~levels
~ have
also been reported to decrease in both men and women during marathon running,80,*08
but in these investigations the lack of homogeneity in the populations
studied, the timing of blood sampling, and the lack of control of dietary intake
may be criticized. Moreover, in a study of men performing moderate bicycle
exercise LH and FSH levels increased, and the increase in LH was enhanced by
the infusion of the opioid blocker n a l ~ x o n e Most
. ~ ~ studies support the view
that in man the concentrations of the gonadotropins LH and FSH, in plasma
do not change during exercise.81,82*101,105
Since most studies have shown that plasma LH and FSH levels do not
change during exercise, one would expect the secretion of the gonadal hormones also to remain constant. Nevertheless, the plasma concentrations of gonadal hormones have been found to increase in exercise, the increase being more
pronounced the higher the work load.36,82,93,105
However, these changes (when
398
EXERCISE ENDOCRINOLOGY
corrected for changes in plasma volume) are, in large part, due to decreased
hepatic blood flow and decreased clearance of the hormones. In line with this,
during exercise the percentage increases in the concentrations of the female
gonadal hormones (estradiol and progesterone), in the follicular (preovulatory)
and in the luteal (postovulatory) phase of the menstrual cycle, are similar. Furthermore, after training, the absolute as well as the percent increase in the
concentrations of both hormones in response to a certain absolute work load is
reduced compared to the pretraining response.
In exercising men, an increase in the concentration of free testosterone
occurs without any change in the percentage of testosterone bound to protein."'
The increase in serum testosterone during prolonged heavy exercise gradually
and after long-term exercise, the testosterone concentration has
returned to or below pre-exercise levels.",'08 The decline probably reflects a
reduced secretion rate and in man has variably been ascribed to decreased
testicular blood flow, increased body temperature, diminished LH levels or
elevated plasma prolactin or cortisol concentrations. However, inhibition of prolactin release by L-dopa has been found not to affect the testosterone response
to moderate exercise.82In exercising rats, the decrease in plasma LH concentration appears to account for the decrease in plasma testosterone level since testosterone secretion can be restored to normal by stimulation with LH.'07
The physiologic significance of the small changes in the plasma concentrations of sex hormones which may be seen during exercise is unknown and does
not appear to be related to exercise-related changes in either glucose or glycogen
rnetab~lism.~~,"~
During daily prolonged exercise, the basal testosterone level has been shown
to decrease in men,'l and lower t e s t ~ s t e r o n eand
~ ~ higher total estrogen levels
have been found at rest in trained compared to untrained male subjects. Levels
of serum LH, FSH, and sex hormone binding globulin were sirmlar in the groups.87
Fertility measures were not reported in these studies, but in a study in which
daily exercise was performed over a five day period sperm production rates did
not change. However, basal testosterone levels did not decrease in this study.
In women training may cause menstrual irregularities, including delayed
menarche, shortening of the luteal phase, anovulatory cycles, oligomenorrhea
and amenorrhea."' Altered menstrual cycle function has been reported during
all kinds of endurance training but the prevalence of amenorrhea seems to be
much higher in runners compared to swimmers or cyclists."' Menstrual irregularties correlate positively with amount of t r a i n i ~ ~ g , ~ ~and
, ~ ~are
' , ' particularly
'~
seen in girls with late menarche and in girls who start training prior to menarche. It is important to note that training-induced menstrual dysfunction is
reversible, and hormone levels and menstrual cycles return to normal when
exercise is reduced or ~ t o p p e d . ' ~
In training women, plasma sex hormone concentrations vary from normallo'
to levels reflecting hypothalamic hypogonadotropia (decreased levels of LH,
FSH, estradiol, and p r ~ g e s t e r o n e ) ' ~ , ~and
~ , " ~correlate well with variations in
the menstrual function, which also range from normal to amenorrhea. In accordance with ovarian hypoactivity, the weight of the ovaries as well as the
activity of enzymes involved in ovarian hormone production have been shown
GALBO
399
to be lower, and the cholesterol and ascorbic acid content of the ovaries higher
in trained rats compared to controls. Athletes with menstrual dysfunction have
a lower mean body weight and less fat than athletes with normal menstrual
f u n ~ t i o n . ~ ' ~However,
,"~
the lower body mass probably do not cause the menstrual irreg~larities.~~,"~
It is also unlikely that the amenorrhea in athletes can
be attributed to hyperandrogenism, hyperprolactinemia, or psychological
s t r e s ~ . ~ ~ In
, ~female
' , ~ ' ~ rats basal serum testosterone levels as well as androgenreceptor binding, are not influenced by training.
In endurance-trained women with normal menstrual cycles there does not
appear to be any problem in becoming pregnant. However, in women with
menstrual and hormonal irregularities the ability to conceive may be reduced.
In those who do become pregnant and continue to exercise up to the preconceptual levels, weight gain is less, delivery occurs earlier, and infants have lower
birthweights but without increased morbidity."'
XIII. THE POSTEXERCISE PERIOD
At the beginning of the recovery period, the metabolic rate, although lower
than during exercise, is still increased, glycogen stores in the exercised muscles
are depleted, excess heat has been stored, and the fluid volume is diminished
and redistributed. Accordingly, there is a need for fuel mobilization, fuel redistribution, cardiovascular adaptation, and conservation of water and electrolytes.
However, the need is less than during exercise. It should be remembered that
the derangement in the body metabolism and composition after exercise is determined by the preceding muscular activity (e.g., with respect to intensity,
duration, and environment), and that complete return to the pre-exercise state
requires rest as well as intake of nutrients and fluid.
After short-term, heavy exercise, derangement of homeostasis is not profound and normalization of plasma hormone levels occurs rather quickly.'16
Immediately after this type of exercise, there may even be a rebound increase
in plasma insulin levels above basal levels, reflecting a sudden diminution of
alpha-adrenergic inhibition of the pancreatic p-cells. After prolonged exhaustive
exercise, the derangement of homeostasis is marked and plasma hormone concentrations only return slowly towards basal v a l ~ e s . ~ ~The
, ' ' ~slow hormonal
recovery reflects the rate with which the stimuli underlying the hormonal changes
are normalized, but may also reflect that a change in the sensitivity of hormonal
secretion to stimulation has developed during exercise. Thus, after a single bout
of prolonged exercise, the insulin concentration in plasma remains low for a
long time, and this kind of exercise also results in a reduced insulin response
to glucose.
XIV. UNIFYING SCHEME FOR THE CONTROL OF THE
HORMONAL RESPONSE TO EXERCISE
The time course of hormonal changes during exercise and in the postexercise period indicates that the regulation of the autonomic neuroendocrine
response to exercise has a fast nervous component and a slow "infernal milieu"
400
EXERCISE ENDOCRINOLOGY
component. The response may be regulated as follows: at the onset of exercise,
impulses from motor centers in the brain, as well as from working muscles,
elicit a work load-dependent increase in sympathoadrenal activity and in release
of some pituitary hormones (GH, ACTH, PRL, possibly TSH). These changes,
in turn, are responsible for modulation of secretion of subordinate endocrine
cells: sympathoadrenal activity depresses insulin secretion, stimulates the reninangiotensin-ADH system, and enhances the secretion of pancreatic polypeptide,
glucagon, and possibly PTH, gastrin, and other hormones as well. ACTH stimulates adrenal cortical secretion. In man the secretion of the gonadotropins is
not influenced by acute exercise and increased concentrations of gonadal hormones are due to decreased clearance.
The state of the organism prior to exercise is an important measure of the
magnitude of the hormonal response. Thus, physical training diminishes the
response of many hormones since their secretion, to a large extent, depends
upon the relative rather than on the absolute work intensity. In contrast, the
concentrations of other hormones are higher during exercise in several conditions in which insulin availability is lower than normal. If exercise is continued, the hormonal changes may be gradually intensified by impulses from
receptors sensing changes in internal milieu, (e.g., in glucose concentrations,
temperature, and intravascular volume). A decrease in plasma glucose concentration is probably the most important signal coupling fuel mobilization to
substrate need.
In principle, the depicted control of the hormonal response to exercise is
similar to that of respiration and circulation, including feed-for~ard''~
as well
as feed-back components. Interestingly, hormonal responses very similar to
those that occur during exercise are seen in other kinds of stress (e.g., psychological stress, hyper- and hypothermia, hypoxia, hypoglycemia, trauma, burn
injury, sepsis, hemorrhage, and surgery). In accordance with the advanced
hypothesis for the control of the hormonal response to exercise, in psychological
stress the stimuli eliciting hormonal changes arise primarily within the brain.
Furthermore, neuroendocrine activity in the brain can be influenced by stimulation of muscle recept01-s~~.
The meaningfulness of the hormonal changes is
not obvious in all of the above-mentioned stress conditions. Although the hormonal response, when elicited by exercise, at first sight appears expedient, it
should not be taken for granted that the hormonal changes are accurately adjusted to the needs of the body.
Our knowledge regarding the hormonal responses to exercise is far from
complete. Much information is still lacking concerning those factors that regulate the changes in hormone secretion and clearance, and of the feed-back control mechanisms. Furthermore, although "new" putative hormones and
neurotransmitters are being continuously discovered, their precise role in the
adaptive changes that occur during exercise remains to be elucidated. Probably,
the most fascinating area of future research lies in the definition and neurochemical characterization of the CNS regulatory pathways involved in the feedforward control of hormonal and, in turn, metabolic responses to exercise. Studies of the control of respiration and circulation in exercise'17 and of the neurochemical basis for the CNS regulation of the autonomic nervous system'ls may
serve as models for such research.
CALBO
401
XV. ACCURACY OF FUEL MOBILIZATION IN EXERCISE
Contractile activity per se directly elicits breakdown of intramuscular glycogen and triglyceride. The mobilization of intramuscular fuel is subjected to
feed-forward regulation and this may not be accurately adjusted to the fuel
needs of the organism. Thus, glycogen breakdown and lactate production in
stimulated perfused muscle are increased, if pre-exercise glycogen levels are
s~pranormal.~~’
During stimulation, glucose uptake is impaired in muscle with
supranormal glycogen concentration compared to muscle with a normal glycogen content but the difference is smaller than the difference in glycogen depletion.”’ It appears that mobilization of intramuscular fuel is not mainly called
on when delivery of exogenous fuel is insufficient. Similarly, other experiments
have shown that combustion of intramuscular fuels may increase with exercise
intensity while muscular uptake of glucose and free fatty acids (FFA) decreases
in spite of increased delivery of these blood-borne metabolites.
The hormonal response to exercise is essentially nondiscriminatory, promoting mobilization of both glycogen and triglyceride from extra- as well as
intramuscular stores. This hormone-mediated fuel mobilization is superimposed
on mobilization of intramuscular stores by contractile activity per se. As previously discussed, the hormonal response to exercise is, to a significant extent,
regulated by feed-forward mechanisms that are intimately related to motor activity rather than to substrate need. Furthermore, the hormonal changes elicited
by exercise are critical to the regulation of the circulation, body temperature,
volume, and osmolality of body fluids, in addition to metabolism. Thus feedback
from nonmetabolic error signals will influence the response of hormones that
have important roles in regulating the metabolic adaptations to exercise. For
instance, increased sympathoadrenal activity elicited by a decrease in the intravascular volume will inhibit insulin secretion. Similarly, the finding of higher
intramuscular glucose-6-phosphate and lactate concentrations during intense
exercise performed at cool versus normal temperatures12’ probably reflects an
“inappropriate” enhancement of glycogenolysis mediated by epinephrine that
is released in response to stimulation of cold receptors.
In accordance with the view that mobilization of extramuscular fuel may
be regulated in a ”feed-forward” fashion rather than by ”feed-back’ mechanisms, it has been shown in running rats that hepatic glycogen is mobilized
and glucose ”forced” upon the exercising muscles at a time when they are rich
in endogenous fuel.121Furthermore, when rats are studied at the same exercise
intensity, oxygen uptake, and muscular glycogen concentration, hepatic glucose
production is higher when liver glycogen stores have previously been increased
by fructose than in experiments in which hepatic glycogen has been depleted
before exercise.lZ2
During exercise of a fixed intensity, the state of the organism immediately
prior to the onset of physical activity (e.g., with respect to nutrition,123degree
of training, plasma hormone concentrations, and level of physical activity) influences the exercise-induced hormonal changes, the fuel depots (e.g., in terms
of size, ,hormone receptors, enzymatic capacity, sensitivity to stimulation) and
the capacity of recruited muscle fibers for metabolism of the different substrates.
Extra- and intramuscular fuels are burned in competition with each other, and
402
EXERCISE ENDOCRINOLOGY
the final choice of fuel depends on availability of substrates and on the capacity
of the metabolizing, energy-yielding enzymatic pathways. Some feed-back inhibition is exerted by the mobilized fuels on the initial enzymatic steps involved
in mobilization of glycogen and triglyceride stores. However, this is not sufficient to allow an accurate adjustment of fuel mobilization to energy demand.
During exercise, fuel may be mobilized in excess of the body's needs. Such fuels
may be restored as evidenced by the accumulation of triglyceride in liver124and
the incorporation of infused radiolabelled glucose in muscular glycogen.125 It
might be argued that excess mobilization is necessary to allow optimal fuel
delivery to the working muscles. However, during prolonged exercise the concentration of FFA in plasma and the supply of FFA to a working muscle group
may increase without an accompanying decrease in whole body RQ or local
muscle RQ,'6,123 indicating that FFA mobilization may proceed beyond the
point at which mobilization limits combustion. However, some reservation about
this interpretation, should be considered. Exhaustion may take place at a time
when triglyceride stores are plentiful, yet may be delayed by exogenous administration of FFA. Clearly, much more information is needed concerning the
balance between feed-forward versus feed-back control of metabolism during
exercise. Nonetheless, presently available evidence would suggest that feedforward control is an important regulatory mechanism that, in certain circumstances, may be maladaptive to the exercising organism.
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