LEADING ARTICLE

Sports Medicine 12 (2): 80-93, 1991 0112-1642/91/0008-0080/$07.00/0 © Adis International Limited. All rights reserved. SP0136

Exercise-Induced Hormonal Changes and their Effects upon Skeletal Muscle Tissue Michael R. Deschenes,1 William J. Kraemer,2 Carl M . Maresh l ,3 and Joseph F. Crivello I I Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, USA 2 Center for Sports Medicine, Pennsylvania State University, University Park, Pennsylvania, USA 3 Department of Sport, Leisure, and Exercise Sciences, University of Connecticut, Storrs, Connecticut, USA

It has long been established that many of the hormones synthesised and secreted by the neuroendocrine system have effects upon skeletal muscle tissue. These effects are generally categorised as catabolic, leading to the breakdown of muscle proteins, or anabolic, leading to the synthesis of muscle proteins. In large part, the size and metabolic state of muscle fibres depend on the circulating concentrations of these hormones. It has also been demonstrated that exercise can induce both short and long term alterations in the blood levels of these hormones. Further, it has been found that different exercise stimuli, i.e. endurance exercise vs heavy resistance exercise, elicit different hormonal responses. This review discusses how endurance and resistance exercise affect circulating concentrations of hormones that are known to have potent anabolic or catabolic effects on skeletal muscle tissue. It should be noted that several hormones have been excluded from this review either because there is limited information available on them with respect to exercise and/or because their effects on muscle tissue are negligible in adults. On the other hand, a somewhat lengthy discussion of growth factors is included in this review. Although research concerning the effects of exercise on serum concentrations of growth factors is sparse, these polypeptides represent an exciting and new field of

study to those interested in muscle growth and maintenance.

1. Testosterone Testosterone is a steroid hormone that has a considerable anabolic effect on muscle tissue. In men, the synthesis of testosterone is almost exclusively controlled by the hypothalamic-pituitarytesticular axis (Hedge et al. 1987). The hypothalamus secretes gonadotrophin-releasing hormone (GnRH) which stimulates the anterior segment of the pituitary gland, located at the base of the brain, to release luteinising hormone (LH) into the bloodstream. The LH then stimulates the Leydig cells of the testis to synthesise and secrete testosterone into the circulatory system. In women, LH stimulates the ovaries to secrete small amounts of testosterone into the bloodstream. Like all steroid hormones testosterone is derived from cholesterol and is not freely soluble in plasma. Consequently, it must bind with plasma proteins or globulins in order to circulate in the blood. During resting conditions, 97 to 99% of the total circulating testosterone is bound to either sex hormone-binding globulin (SHBG) or albumin (Hedge et al. 1987; Martin 1985). The remaining I to 3% is the metabolically active 'free' form (Hedge et al. 1987; Martin 1985). Testosterone's

Exercised-Induced Hormonal Responses

anabolic effects result from increases in protein synthesis and decreases in the rate of protein catabolism within the muscle fibre (Hedge et al. 1987; Pearlman & Crepy 1967). The putative mechanism involved is a stimulation in the transcription of the cell's DNA. Testosterone is permeable to the cell's plasma membrane because it is lipid-soluble and cellular membranes are comprised of a lipid bilayer (Hedge et al. 1987). Once inside the cell, testosterone binds with receptors found within the cytosol of the cell. These hormone-receptor complexes then increase the transcription of genes located on the nuclear DNA that code for the synthesis of contractile proteins (Hedge et al. 1987; Martin 1985). The mRNA that results from this transcription is translocated from the nucleus to the cytosol where protein synthesis, e.g. translation, occurs (Hedge et al. 1987; Pearlman & Crepy 1967).

1.1 Acute Responses to Exercise (table /) Several studies have indicated that exercise induces an acute elevation in circulating testosterone levels (Kraemer 1988; Kuoppasalmi et al. 1980; Maresh et al. 1988). It appears that the intensity, duration and mode of physical activity are important factors in determining testosterone response to exercise. When subjects were asked to run for 45 minutes at a high speed (3.3 min/km) and for 90 minutes at a moderate speed (4.3 mint km) they demonstrated a 7 and 21 % increase in plasma testosterone, respectively (Kuoppasalmi et al. 1980). It is believed that the elevations in plasma testosterone immediately following exercise result from the decreased rate of hepatic clearance that is typically observed during prolonged exercise (Galbo 1985; Kuoppasalmi et al. 1980). However, during recovery from exercise of a submaximal intensity plasma testosterone concentrations fall dramatically. Within 30 minutes after exercise, plasma testosterone levels were found to be below pre-exercise concentrations and 3 hours after exercise they were 41 % lower than the original resting levels (Kuoppasalmi et al. 1980). In contrast, running at maximal intensity for a short duration does not appear to affect total tes-

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tosterone plasma concentrations. When male subjects sprinted 20, 40 and 60m with 30 seconds of rest between each run there were no significant changes in plasma testosterone levels (Kuoppasalmi et al. 1980). Wilkerson et al. (1980) were also able to demonstrate that exercise intensity affects plasma testosterone. Male subjects exercised at 30, 45, 60, 75 and 90% of their maximal oxygen consumption CV02max) for 20 minutes. Work intensity was found to be positively correlated with increases in plasma testosterone concentrations. Additionally, these subjects showed immediate, but temporary elevations in plasma testosterone subsequent to exercise. Again, it was concluded that these acute increases in plasma testosterone following exercise were due to the decreased rate of hepatic clearance. Weight-training is also known to increase plasma concentrations of testosterone immediately following exercise (Cumming et al. 1987; Kraemer et al. 1988). It is both interesting and important to note that different weight-training protocols may induce different testosterone responses. In a study conducted by Kraemer et al. (1988) it was shown that several heavy resistance exercise protocols produce acute increases in serum testosterone concentrations. Each of the exercise protocols examined resulted in different response patterns during and for 2 hours following exercise. Still, each protocol produced increases in circulating testosterone levels during and/or after the exercise session. Furthermore, it appears that some heavy resistance exercise protocols may induce elevations in testosterone later into recovery than had been previously demonstrated, e.g. 90 to 120 minutes after exercise. 1.2 Long Term Responses to Exercise

(table II) Exercising on a regular basis has been demonstrated to affect resting levels of testosterone (Haakinen et aI. 1988; Wheeler et aI. 1984). As with acute testosterone responses, it appears that long term testosterone responses to exercise are determined by the mode, intensity and duration of the exercise featured in the training programme.

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Table I. Acute serum testosterone responses to exercise Reference

Sex of subjects

Mode of exercise

Intensity

Duration

Change in testosterone levels (%)

Guezennec et al. (1986)

Male

Weight-training

70% MVC

8 repetitions, 15 sets

+3

Shangold (1984)

Female

Treadmill running

Self-selected

30 min

+37

Grossman et al. (1984)

Male

Cycle ergometer

40 and 80% MAP

40 min

+29

Cumming et al. (1987)

Female

Weight-training

Point of muscular failure

10 repetitions,

+20

18 sets

Maresh et al. (1988)

Male

Cycle ergometer

50% MAP

45 min

+30

Kuoppasalmi (1980)

Male

Running

3.3 min/km

45 min

+21

Kuoppasalmi (1980)

Male

Running

4.3 min/km

90 min

+7

Wilkerson et al. (1980)

Male

Treadmill running

Gradual increase up to 90% MAP

20 min

+11

Wilkerson et al. (1980)

Male

Treadmill running

100% MAP

8 min

+21

Abbreviations:

MVC

= maximal voluntary contraction;

MAP

= maximal aerobic power.

Wheeler et al. (1984) found that male distance runners who train an average of 64km per week experience a 17% decrement in resting concentrations of plasma testosterone compared to agematched controls. The mechanism underlying this decrease is thought to be a reduction in testicular secretion caused by an alteration in the biosynthetic pathway of androgens, and/or an impairment of the involved enzymes due to the stress imposed by physical activity (Aono et al. 1976; Nakashima et al. 1975). More recently, it has been reported that endurance trained male athletes demonstrate a 30% reduction in serum testosterone concentrations (Hackney et al. 1990). In this study, it was suggested that the mechanism involved in the decreased resting testosterone levels is related to alterations in the hypothalamic-pituitary-testicular axis. Specifically, endurance trained men show attenuated LH responses following stimulation by GnRH. The diminished LH response leads to reduced testosterone production by the Leydig cells. It has also been found that endurance-trained

females experience reduced resting levels of serum testosterone (Keiser 1986; Kuoppasalmi et al. 1980). At this time, no mechanism for these findings has been identified. However, the data regarding endurance training and decreased serum testosterone concentrations must be viewed with caution. There is increasing evidence that reduced resting testosterone concentrations are symptomatic of overtraining. Recent research (Strauss et al. 1985; Tegelman et ai, 1990) has demonstrated that during the off season competitive athletes' resting serum testosterone levels return to values observed in age-matched untrained individuals. This is true despite the fact that these athletes continue to train in the off season, albeit with lower intensities and volumes. In fact, several reports have suggested using diminished resting serum testosterone concentrations and decreased serum testosterone to cortisol ratios as indicators of overtraining (Aldercreutz et al. 1986; Busso et al. 1990; Haakinen et al. 1985). In contrast to endurance training, weight-train-

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Exercised-Induced Hormonal Responses

ing has been demonstrated to increase resting levels of testosterone (Haakinen et al. 1985, 1988). Haakinen et al. (1987) have found significant correlations between increases in strength and elevations in the free to bound testosterone ratio. Additionally, it was shown that highly strengthtrained athletes have higher concentrations of total testosterone in the blood than non-weight-trained control subjects (Haakinen et al. 1985, 1988). Sim-

ilar to endurance trained athletes, reduced resting serum testosterone levels in resistance trained athletes may reflect a state of overtraining. Haakinen et al. (1987) measured serum hormonal responses in weightlifters during their training leading up to a competition. It was found that resting serum testosterone levels were significantly decreased during the 2-week period that these athletes were undergoing their most stressful training. In addition, a

Table II. Training-induced changes in resting serum testosterone levels Reference

Sex of subjects

Mode of exercise

Intensity

Duration

Change in testosterone levels (%)

Wheeler et al. (1984)

Male

Running

Self-selected

64 km/wk

-17

Cumming et al. (1987)

Female

Weight-training

Point of muscular failure

8wk

+36

Tegelman et al. (1990)

Male

Skiing/orienteering

Off-season. low intensity training

+21

Tegelman et al. (1990)

Female

Skiing/orienteering

Off-season low intensity training

-21

Busso et al.

Male

Weight-training

80% MVC. 230 reps/wk

15wk

+52

Busso et al. (1990)

Male

Weight-training

80% MVC. 230 reps/wk

51wk

+17

Seidman et al. (1990) Seidman et al. (1990)

Male

Aerobic exercise

5 days/wk. 6wk

+29

Male

Aerobic exercise

5 days/wk. 12wk

-21

Seidman et al. (1990)

Male

Aerobic exercise

5 days/wk. 18wk

+2

Hackney et al. (1990)

Male

Running

Self-selected

18 km/day. 16y

-48

Haakinen et al. (1985)

Male

Weight-training

70-100% MVC. 570 reps/wk

16wk

+25

Haakinen et al. (1985)

Male

Weight-training

70-100% MVC. 570 reps/wk

24wk

0

Haakinen et al. (1990)

Female

Weight-training

40-80% MVC. 300 reps/wk

16wk

-18

Haakinen et al. (1988)

Male

Weight-training

Self-selected

3-5 days/wk. 24mo

+27

(1990)

Abbreviation: MVC

= maximal voluntary contraction.

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84

concomitant reduction in the testosterone to cortisol ratio, and the free to bound testosterone ratio occurred. During these same 2 weeks of intensive training these athletes also showed a decrement in weightlifting performance. This led the authors to suggest that decreased resting serum testosterone levels and testosterone to cortisol ratios are indicative of overtraining. A more recent study conducted by Busso et al. (1990) lends support to this suggestion. The hormonal responses and athletic performances of weightlifters were measured during a 51-week training programme. Again, a significant correlation between resting serum testosterone changes and weightlifting performance was noted. In conclusion, it has been demonstrated that weight-training can elicit increases in resting serum testosterone concentrations and free-to-bound testosterone ratios (Busso et al. 1990; Haakinen et al. 1988). However, a state of overtraining in weighttrained athletes may result in reductions of these serum parameters. 1.3 Sex-Related Differences The difference in muscular hypertrophy observed between men and women has been attributed mainly to higher plasma concentrations of testosterone in males (Hedge et al. 1987). Differences between men and women exist in the location of testosterone production; as a result, testosterone response to exercise may be sex-specific. In women, approximately 50% of the circulating testosterone is produced in the adrenal cortex. However, of the total amount of testosterone produced in men, only a small proportion is synthesised in the adrenal cortex (Cumming et al. 1987). Cortisol, a catabolic glucocorticoid, is also synthesised in the adrenal cortex. The release of cortisol into the circulation is stimulated by adrenocorticotrophic hormone (ACTH), a polypeptide synthesised in the anterior segment of the pituitary gland. Exercise of a sufficient intensity, greater than 70% of maximum oxygen consumption, induces an increase in plasma ACTH and consequently in plasma cortisol (Shangold 1984). There is close

proximity within the adrenal glands between the cortisol-producing cells located in the zona fasiculata and the zona reticularis, and the androgenproducing cells found in the zona reticularis. Due to their proximity, stimulation of the cortisol-producing cells may cause the release of testosterone from the androgen-producing cells. Since half the circulating testosterone in women is produced by the adrenal cortex, increases in ACTH and cortisol are associated with elevated levels of plasma testosterone in women (Cumming et al. 1987; Shangold et al. 1981). Conversely, in men an elevation in cortisol has been associated with decreased testosterone levels. It has been suggested that increased levels of cortisol may act directly upon the testis to impair the biosynthesis of testosterone (Wheeler et al. 1984). Another gender difference regarding testosterone is that women have a greater amount of their total testosterone bound to SHBG than do men (Wheeler et al. 1984). This is significant because as mentioned previously, only free testosterone is biologically active. However, one study has found that women who participate regularly in weight-training programmes show increases in total testosterone and decreases in bound testosterone following exercise (Cumming et al. 1987). A more recent study investigated the effects of a short term (4-week) weight-training programme including only lower body exercises on resting serum hormone concentrations in women (Haakinen et al. 1990). It was found that this exercise regimen did not alter resting serum testosterone levels in women, but a significant increase in the free to bound testosterone ratio was noted. As with men, these increased free-to-bound testosterone ratios were positively correlated with increased force production. In summary, it can be said that aerobic exercise of a sufficient intensity and duration does result in elevated testosterone levels during and immediately after exercise in both men and women. Weight-training exercise also induces plasma elevations of testosterone in both men and women. However, not all weight-training protocols appear

Exercised-Induced Hormonal Responses

to be equally potent in bringing about these changes in circulating testosterone concentrations.

2. Growth Hormone (Somatotrophin) Growth hormone (GH) is a peptide hormone synthesised in the anterior segment of the pituitary gland. GH plays a crucial role in the growth and development of bone, connective, visceral, adipose and muscle tissue (Hedge et al. 1987; Martin 1985). The effects of GH can be either direct or indirect (Hedge et al. 1987). Our understanding of the direct effects of GH may be enhanced due to the recent isolation of the GH receptor (Leung et al. 1987). It has been suggested that GH may bind to receptors on the plasma membrane of muscle tissue and have a direct anabolic effect. Conversely, most data indicate that the anabolic effects of GH upon muscle tissue are indirect and are carried out by a family of polypeptides called somatomedins (Hedge et al. 1987; Kraemer 1988). These polypeptides are synthesised in the liver and released into the blood upon stimulation of the liver by GH. The somatomedins then bind to receptors found on the plasma membrane of the muscle cell and carry out the growth-promoting effects attributed to GH. A more complete discussion of somatomedins will occur in section 3. Regardless of whether the effects of GH are direct or indirect, it promotes hypertrophy by increasing amino acid transport into the cell and incorporating these amino acids into protein (Daughaday & Rotwein 1989; Fiorini 1985).

85

ergometer, a 166% elevation in serum GH was observed. The data concerning GH responses during recovery from exercise are equivocal. For example, VanHelder et al. (1986) found that serum GH levels were highest when measured 8 minutes into recovery. Conversely, research conducted by Farrell et al. (1986) demonstrated that serum GH levels had already started to fall immediately after exercise and continued to decline throughout recovery. Bunt et al. (1986) also showed that serum GH begins to fall immediately following exercise. However, it must be pointed out that these 3 studies employed different exercise protocols. Thus, conclusions concerning GH responses during recovery cannot be made until more studies are conducted to specifically investigate the effects of exercise duration and intensity upon serum GH concentrations during re€overy from aerobic exercise. Research has shown that heavy resistance exercise can bring about acute changes in serum GH concentrations (Kraemer 1988; Kraemer et al. 1988). As with aerobic exercise, it appears that the intensity at which heavy resistance exercise is performed determines the GH response. Research has indicated that when exercising with 70 to 85% of the subject's I repetition maximum resistance, serum somatotrophin is significantly elevated (Kraemer et al. 1988). However, when the resistance to be lifted was reduced enough to allow subjects to complete 21 repetitions no change in serum GH was observed (Kraemer et al. 1988). 2.2 Long Term Responses to Exercise

2.1 Acute Responses to Exercise (table III) It has been demonstrated that GH levels are elevated during aerobic exercise, that these elevations are positively correlated with exercise intensity and that GH levels typically remain elevated for some time following exercise (Bloom et al. 1976; Galbo 1985). VanHelder et al. (1986) reported a 145% increase in serum GH when subjects exercised at 40% of their V02 max on a bicycle ergometer. When Farrell et al. (1986) had subjects exercise at 70% of their V02 max on a bicycle

There are data suggesting that regular endurance training affects acute GH response to aerobic exercise. Most of the available research indicates that well-trained individuals show a blunted GH response during exercise (Bloom et al. 1975; Galbo 1985; Hartley et al. 1972). Contrary to these findings, Bunt et al. (1986) found that well-trained men showed more pronounced GH elevations during exercise than untrained age-matched control subjects. Curiously, there may be gender differences in

86

Sports Medicine 12 (2) 1991

Table III. Acute growth hormone responses to exercise

Reference

Sex of subjects

Mode of exercise

Intensity

Duration

Change in testosterone levels (%)

Johannessen et al. (1981)

Male

Treadmill running

70% MAP

30 min

+600

Johannessen et al. (1981)

Male

Treadmill running

70% MAP

60 min

+400

Hartley et al. (1972)

Male

Cycle ergometry

75% MAP

40 min

+326

Grossman et al. (1984)

Male

Cycle ergometry

80% MAP

20 min

+263

Farrell et al. (1986)

Male

Cycle ergometry

70% MAP

30 min

+166

Van Helder et al. (1986)

Male

Cycle ergometry

40% MAP

40 min

+120

Bunt et al. (1986)

Male

Treadmill running

60% MAP

60 min

+650

Bunt et al. (1986)

Female

Treadmill running

60% MAP

60 min

+400

Maresh et al. (1988)

Male

Cycle ergometer

50% MAP

45 min

+333

Kraemer et al. (1990)

Male

Weight-training

5 repetitions, 3-5 sets/exercise

155 reps

+300

Kraemer et al. (1990)

Male

Weight-training

10 repetitions 3 sets/exercise

240 reps

+800

Abbreviation: MAP = maximal aerobic power.

the effects of training upon GH response. Unfortunately, the existing research concerning this matter is conflicting. Gambert et al. (1981) found that men and women show similar GH elevations during exercise. Conversely, Frantz and Rabkin (1965) reported that the exercise-induced increase in serum GH is generally greater in women than in men. Bunt et al. (1986) found that women, whether they were trained or not, had higher resting serum GH concentrations than age- and fitness-matched men. Furthermore, it was demonstrated that while training status did affect GH response to exercise in men, trained and untrained women exhibited similar GH responses to exercise. It should be noted

that each of these studies employed different exercise protocols; this may account for the different results. While it has been found that heavy resistance training may bring about increases in serum GH levels immediately following exercise, there are no data to indicate that resistance training elevates resting levels of GH. Haakinen et al. (1985) asked subjects to participate in a strength-training programme for a duration of 24 weeks. At the end of this training regimen it was determined that the subjects had significantly improved their strength, yet no changes in resting serum GH concentrations were found.

Exercised-Induced Hormonal Responses

2.3 Stimulus of GH Response The mechanism by which exercise stimulates elevated levels of serum GH is a point of some conjecture. Hypoxia, hypoglycaemia, decreased insulin levels and increased lactate concentrations have all been posited as stimuli leading to increased GH release (Grossman et al. 1984; Miller et al. 1984; VanHelder et al. 1986). Another mechanism by which exercise may elevate serum GH is related to the impact that exercise has on somatostatin, a hormone that inhibits the secretion of GH from the pituitary gland. It has been suggested that the pituitary gland undergoes increasing sensitivity to somatostatin's releasing factor (SRIF) with age. Cuttler et al. (1986) indicate that the levels of SRIF are at their highest at the same time that GH levels are most pronounced. This implies the presence of a feedback loop between these two hormones such that the effects of GH are mitigated by concurrent elevations in SRIF. During intense physical activity it has been shown that ~-endorphins are released into the blood (Borer et al. 1986; Farrell et al. 1986). It has been hypothesised that these endogenous opioids are able to offset the inhibitory effect of SRIF upon somatotrophin (Borer et al. 1986). Like other stressrelated hormones there exists an exercise intensity threshold for the secretion of ~-endorphins. The work of Donevan and Andrew (1987) indicates that when exercising on a bicycle ergometer, an exercise intensity of 50% OfV02 max is not associated with any changes in the concentration of circulating ~­ endorphins. However, when exercising at 75% of V02 max there is a significant increase in circulating ~-endorphins and there is a progressive rise in these levels as exercise intensity increases (Donevan & Andrew 1987). The recent work of Kraemer et al. (1989) demonstrates that short term, high intensity exercise may elicit different ~-endorphin responses than those seen with lower exercise intensities, e.g. below 100% OfV02 max. In this study a short burst of high intensity (115% of V02 max) exercise performed on a bicycle ergometer induced significant elevations in ~-endorphins. However, at even higher work intensities (175, 230 and 318%

87

of V02 max) no alterations in serum endogenous opioids were reported. These data indicate that the interplay between exercise intensity and duration is critical to our understanding of hormonal responses to exercise. A greater understanding of exercise-induced changes in {j-endorphin secretion is important because, as previously mentioned, these endogenous opioids may act to ameliorate the effects of somatostatin upon GH release. This may be enhanced in well-trained individuals, since exercising on a regular basis may increase opioid receptor sensitivity (Donevan & Andrew 1987). Another mechanism by which exercise may increase somatotrophin secretion directly relates to the exercise-induced mobilisation of calcium. It has been established that exercise of a moderate intensity, e.g. 40% of V02 max, results in an elevation of serum calcium and that the degree of this elevation is related to exercise intensity (Ljunhall et al. 1984; Vora et al. 1983). Curiously, this exerciseinduced calcium mobilisation is not accompanied by an increase in parathyroid hormone concentration (Vora et al. 1983). This is unexpected because under nonexercise conditions calcium elevations are typically preceded by increased parathyroid hormone levels. Although there is ambiguity concerning the mechanism bringing about increases in serum calcium during exercise, there are some data suggesting that the accumulation of lactate may be involved (Miller et al. 1984). Conversely, other research demonstrates that there is an increase in serum calcium before the onset of lactate accumulation (Vora et al. 1983). Regardless of the mechanism involved, this blood-borne calcium may lead to an increase in the release of GH during exercise. The pituitary gland secretes GH in response to the binding ofGH-releasing factor (GRF) with its receptors in the pituitary gland. It has been found that the early phase of GH release elicited by GRF is dependent upon calcium mobilisation (Login et al. 1986). It has been postulated that the additional amounts of calcium in the blood may increase calcium uptake by the pituitary cells upon GRF binding. This intracellular calcium can then be used as a second messenger to evoke increased

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88

DNA transcription within the cells of the pituitary gland. This then results in enhanced GH synthesis and secretion from the pituitary gland (Login et al. 1986). To summarise, there is no question that aerobic exercise of sufficient intensity, e.g. 40% of -VU 2 max, elevates serum GH concentrations during exercise and possibly during recovery from exercise. It has also been demonstrated that acute GH elevations can be induced by weight-training exercise. Unfortunately, at this time it is not possible to identify the precise mechanism causing these changes in serum GH concentrations. Several possibilities have been examined here. As stated earlier, it is believed that the anabolic effects ofGH are actually carried out by somatomedins. As such, it is difficult to examine the effects of GH without the concomitant investigation of somatomedins.

3. Somatomedins (Insulin-Like Growth Factors) The discovery and identification of a family of polypeptides called somatomedins have added much to our understanding of the differentiation and development of muscle and connective tissue. It had been thought that these somatomedins could only be synthesised and released by the liver. However, recent evidence suggests that these substances can be produced by other types of cells including skeletal muscle fibres (Daughaday & Rotwein 1989). 3.1 Nomenclature At this time there seems to be no unanimity concerning the nomenclature and categorisation of these substances. However, the polypeptide that some call insulin-like growth factor I has been found to be identical to the substance others call somatomedin C (SM-C). Insulin-like growth factor II and somatomedin A (SM-A) show structural similarities not only with each other but also with another polypeptide called multiplication-stimulating activity (MSA). These substances have been shown to increase the rate of cell proliferation in cell culture studies (Ewton et al. 1987; Ewton & Fiorini

1981; Fiorini et al. 1986). Although somatomedin B (SM-B) has been identified, it plays no role in either myoblast proliferation or differentiation (Ewton & Fiorini 1980). Indeed, it is now believed that SM-B does not exist and that its identification was probably the result of procedural artefact during biochemical analysis. 3.2 Anabolic Effects of SM-C Serum concentrations of SM-C have been demonstrated by some to be inversely related to GH levels (Yamashita & Melmed 1986). As serum GH levels decrease, SM-C serum levels increase leading some to believe that SM-C mediates the anabolic effects of GH on skeletal muscle tissue (Hedge et al. 1987; Yamashita & Melmed 1986). It has been proposed (Fiorini 1985) that the anabolic effects of GH are restricted to mature, multinucleated myotubes and muscle fibres. During the myoblast stage of development and immediately following cell differentiation it is SM-C, not GH, that plays the critical anabolic role (Fiorini 1985). The effects of somatomedins could be accounted for by the strong amino acid homology between these substances and insulin. Insulin is known to have anabolic effects on skeletal muscle tissue and it has been found that insulin can crossreact with SM-C receptors (Beguinot et al. 1985). Despite this fact, Ewton and Fiorini (1980) have found that in rat myoblast cell cultures insulin will induce cell proliferation and differentiation only when used in supraphysiological concentrations. However, SM-C does cause cell proliferation and differentiation when added in normal physiological concentrations. Ewton and Fiorini (1980) were also able to prove that GH was not able to stimulate either myoblast proliferation or differentiation. But a note of caution should be expressed at this point. Although cell culture studies are useful and informative, they create an artificial biological environment and one should be apprehensive about equating data collected from in vitro studies to what occurs in the intact organism. The in vivo work of Daughaday et al. (1982) confirms the importance of somatomedins upon

89

Exercised-Induced Hormonal Responses

cellular development. A technique was devised allowing the detection of SM-C in rats both in the fetal and postnatal stages. It was found that SM-C is present throughout fetal, neonatal and adult stages. MSA levels gradually rose from the nineteenth day of gestation until the fifth day of postnatal life. By the twentieth day following birth, MSA levels declined to the point where they were equal to those found in the adult rat. 25 days following birth SM-C and insulin had the greatest impact upon tissue growth. This may be due to the fact that during cell differentiation and the development of myotubes there is a sharp increase in the number of insulin receptors. This could be the result of changes in gene expression or by conformational alterations in the cell membrane leading to an increased exposure of already existing insulin receptors (Beguinot et at. 1985). With the demise of MSA soon after cell differentiation occurs, SMC along with insulin have decreased competition for binding of the insulin receptors. Because insulin has a greater affinity for these receptors than does SM-C, insulin is believed to play the primary, but not exclusive, anabolic role in mature muscle fibres. 3.3 Response to Exercise Recent studies have investigated SM-C responses to weight-training (Kraemer et al. 1991). It was found that different weight training protocols elicit different SM-C responses both during and after the exercise session. A weight-training regimen featuring fewer repetitions with greater resistance brought about significant elevations in serum SM-C levels only during the recovery period. These increases persisted for up to 90 minutes following the cessation of exercise. On the other hand, a weight-training session including a greater number of repetitions with less resistance and shorter rest intervals induced significant increases in serum SMC concentrations both during exercise and for up to 90 minutes following exercise (Kraemer et at. 1991). Responses in serum SM-C levels to resistance training appear to be sex-specific. Age-matched men

and women performed the same weight-training protocol; equal resistance was determined relative to individual single repetition maximums. Women demonstrated elevations in serum SM-C concentrations both during and for up to 60 minutes after exercise. Conversely, men showed no increases in serum SM-C levels during exercise, but increases were noted for up to 90 minutes following exercise (Kraemer et at. 1991). 3.4 Additional Growth Factors Our discussion of myoblast proliferation and differentiation would be incomplete if 3 additional growth factors were not addressed. Epidermal growth factor (EGF), fibroblast growth factor (FGF) and transforming growth factor B (TGF-B) have been identified and investigated. EGF has been shown to stimulate the release of somatomedins from hepatocytes (Richman et at. 1980). FGF seems to have a relatively minor effect upon myoblast proliferation (FIorini et at. 1986), and TGF-B performs significant regulatory activities in cell differentiation, growth and function (FIorini et at. 1986). Again using rat myoblast cultures, TGF-B was found to inhibit the fusing of these myoblasts into myotubes (FIorini et at. 1986). TGF-B achieves this by forcing the myoblasts to re-enter the cell cycle and continue proliferation rather than undergoing fusion in the Gap phase of the cell cycle. It has been suggested that the reason for this is to prevent myoblasts from fusing into myotubes at a period in development when myoblast proliferation is essential to form the initial muscle mass necessary to ensure successful myoblast fusion (FIorini et at. 1986; Roberts et at. 1983).

4. Insulin Insulin is a protein hormone secreted by the B cells of the islets of Langerhans within the pancreas. Recent evidence indicates that insulin plays a greater role in protein metabolism than was once thought. It has been found that insulin increases the rate of amino acid uptake by skeletal muscle as well as other tissues (Hedge et al. 1987). Perhaps

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more importantly, insulin decreases the rate of protein degradation within muscle tissue. The net result of these actions is an anabolic or protein building effect within skeletal muscle tissue. Alternatively, it has been postulated that insulin might not play a direct role in anabolism but rather it maintains muscle fibres in a viable, healthy condition, thereby allowing them to grow rather than actually stimulating muscle growth (Fiorini 1985).

4.1 Acute Responses to Exercise Insulin and GH have antagonistic effects upon each other. Given this fact, the increased GH levels seen during exercise may be at least partly attributed to the reduced levels of insulin observed during exercise. The available research indicates that during exercise plasma insulin concentrations are decreased except when the exercise stimulus approaches its maximal intensity, i.e. 90% OfV02 max (Galbo 1985). However, it appears that an individual's level of fitness may affect the degree of this exercise-induced insulin reduction. Although plasma insulin reductions are observed in welltrained athletes during mild and moderate exercise intensities, the extent of their reductions is not as pronounced as those seen in untrained individuals (Bloom et al. 1976). 4.2 Long Term Responses to Exercise

Aerobic exercise facilitates the body's ability to respond to insulin. Sato et al. (1986) have shown that well-trained subjects have greater insulin sensitivity than untrained subjects. It has also been demonstrated that even a single bout of exercise can increase both the sensitivity and responsiveness of skeletal muscle tissue to insulin (Richter et al. 1989). However, it has been found that these effects are localised to the contracting muscles and do not extend to the nonexercised muscle tissue (Richter et al. 1989). The conclusion drawn from these data is that the enhanced insulin responsiveness (greater response to a maximal insulin stimulus) and sensitivity (decrease in the insulin concentration required to elicit 50% of the maximal

response) are brought about by a local muscular contraction-induced mechanism (Richter et al. 1989). Unfortunately, the precise nature of this mechanism remains a mystery at this time. Other data indicate that exercise, while augmenting insulin sensitivity and responsiveness, does not affect the amount of insulin bound to the plasma membrane of muscle cells (Webster et al. 1986). Thus, muscular contractions increase insulin sensitivity and responsiveness due to the amplification of intracellular events. 4.3 Developmental Effects Recent data have shown that not only does insulin promote anabolic processes in mature muscle tissue, it also has a greater function in cell differentiation than previously thought. In cell culture studies, myoblasts were able to bind insulin at all stages of development. This implies that insulin, along with somatomedins, is essential for the differentiation of myoblasts into mature, multinucleated myotubes.

5. Catecholamines Catecholamines are substances released by the adrenal medulla upon stimulation by the sympathetic branch of the autonomic nervous system. The release of these catecholamines elicits the physiological phenomenon commonly known as the 'fight or flight response'. Research indicates that both endurance exercise and heavy resistance exercise induce elevated plasma catecholamine concentrations (Fiorini 1985; Galbo et al. 1975; Kraemer et al. 1985). During aerobic exercise increases in plasma adrenaline (epinephrine) and noradrenaline (norepinephrine) concentrations are directly related to exercise intensity (Galbo 1985; Galbo et al. 1975; Schwarz & Kindermann 1990). This is significant in that adrenaline stimulates amino acid uptake by skeletal muscle fibres (Fiorini 1985; Grossman et al. 1984). It has also been demonstrated that there is a continued elevation of adrenaline during recovery from exercise. However, this information should be

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viewed with some caution. Increased amino acid uptake by the cell does not necessarily lead to increased protein synthesis by that cell (Horini 1985). It may be that these amino acids enter the cell in order to be used as energy substrates. Adrenaline also has some effects that may indirectly alter protein metabolism. It is known to inhibit the release of insulin during exercise (Grossman et al. 1984; Wilmore 1976), but at exercise intensities that are 100% of V02 max this antagonistic effect is abated (Galbo 1985; Galbo et al. 1975). In addition, adrenaline acts directly upon muscle tissue to produce lactate which, in turn, stimulates GH secretion (Wilmore 1976).

6. Glucocorticoids Cortisol is a member of a family of steroid hormones released by the adrenal cortex called glucocorticoids. Cortisol has been found to have catabolic effects upon muscle tissue (Hedge et al. 1987; Martin 1985). Both high intensity aerobic exercise and heavy resistance exercise elicit significant increases in cortisol (Haakinen et al. 1985; Maresh et al. 1988; Schwarz & Kindermann 1990). Cortisol induces the breakdown of cellular proteins, thereby liberating amino acids which can then undergo gluconeogenesis in the liver (Hedge et al. 1987). It has recently been demonstrated that an individual's training status can alter the response of cortisol to exercise (Bloom et al. 1976; Haakinen et al. 1985). A well conditioned athlete will experience a less pronounced cortisol elevation during exercise than will an unconditioned individual. It has been postulated (Busso et al. 1990; Haakinen et al. 1987) that elevated resting serum concentrations of cortisol and/or diminished testosterone to cortisol ratios are indicative of overtraining. It has been demonstrated that athletes experience decrements in performance during periods of increased resting plasma cortisol concentrations (Busso et al. 1990; Haakinen et al. 1990, 1987; Seidman et al. 1990). Curiously, it has been observed that at least one type of glucocorticoid may have anabolic effects. Guerriero and Horini (1980) using rat myoblast cell

cultures, have found that dexamethasone increases myoblast proliferation, although it does not bring about the differentiation of these myoblasts into mature myotubes. Again, these data should be viewed with caution since cell cultures were utilised and the results may be species-specific and restricted to only a certain stage of development.

7. Conclusion The neuroendocrine system plays an integral function in the development and maintenance of muscle tissue. Numerous investigations have confirmed the effects of both aerobic exercise and heavy resistance exercise upon the neuroendocrine system. Although there has been great progress in the area of exercise and neuroendocrinology, many questions regarding hormonal responses to exercise remain unanswered. In particular, there is a need for additional research that will reveal the specific mechanisms by which different exercise protocols induce hormonal responses.

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Correspondence and reprints: Michael R. Deschenes, Department of Physiology and Neurobiology, U-42, The University of Connecticut, Storrs, CT 06269, USA.