Muscular Adaptations to Resistance Training With Special Emphasis on Muscle Fiber and Whole Muscle Hypertrophy
By Mike Croskery - Re-Edited 1998INTRODUCTION
Resistance training has seen a marked rise in participation over the past number of decades. From its increase in popularity during the late 1800’s, lifting weights has become one of the most popular forms of exercise today. It can enhance athletic performance through increasing muscle mass and strength and it can help in the rehabilitation process following an injury. These results are all due to the increases in tension that the working muscles experience as they try to work against a certain amount of resistance (Tesch, 1988). Not only does the muscle respond by getting larger, but muscle strength also becomes specific to that movement (Morrisey, Harman, & Johnson, 1995). In other words, you can be strong lifting 100 pounds one way, but try to lift that 100 pounds in a different fashion and you may find yourself not nearly as strong.
In most cases, certain adaptations that occur will result in the muscle being better able to handle the higher levels of stress placed upon it. These muscular adaptations take place in the individual muscle fibers and surrounding tissues that make up the muscle as a whole. One such adaptation is an increase in muscle fiber size (termed hypertrophy) which can ultimately lead to increases in whole muscle mass and lean body weight (Katch, Katch, Moffat, & Gittleson, 1980). Resistance training has also been shown to increase the number of muscle fibers per muscle (Larsson & Tesch, 1986; Tesch & Larsson, 1982), change the concentrations of cellular structures such as mitochondria (MacDougall et al., 1979; Alway, MacDougall, Sale, Sutton, & McComas, 1988), as well as cause changes in the absolute volume of connective tissues (Viidik, 1986).
A number of complex cellular reactions control whole muscle and muscle fiber hypertrophy. It is these cellular reactions that ultimately control the level of protein synthesis and degradation. The difference between protein synthesis and protein degradation in turn determines the extent of hypertrophy. This review examines the mechanisms and the activation of the processes of protein synthesis and protein degradation. Also investigated are the cellular, hormonal, and workload factors that contribute to this process.
Increases in muscle fiber number appear to occur due to high levels of stress being placed upon the working muscle (Abernathy, Jürimäe, Logan, Taylor, & Thayer, 1994). Satellite cell activity, fiber splitting, and the effects of increased workload are the main factors that control the extent of hyperplasia. Hyperplasia and muscle fiber hypertrophy are the main contributors to whole muscle hypertrophy. However, other factors such as intramuscular energy stores, fluid content, and connective tissue can contribute to this as well. This article contains explanations on hyperplasia and related factors that ultimately contribute to muscle hypertrophy.
RESEARCH METHODS USED IN EXAMINING HYPERTROPHY AND HYPERPLASIA
In the field of muscle research, there are a variety of scientific methods used to determine the extent of muscle hypertrophy and hyperplasia in response to resistance training. Most experiments examining the effects of resistance training on muscle growth and increases in muscle fiber number (otherwise known as hyperplasia) involve tissue from either human or animal subjects. Research with animal subjects typically involves removal of the exercised muscle and comparing it to the pre-experimental levels of the same muscle in the control animal. The two muscles then undergo various comparisons to examine the extent of muscle fiber and whole muscle hypertrophy.
Existing research show that hyperplasia (increases in muscle fiber number) does occur in animals (Alway, Gonyea, & Davis, 1990). The issue if hyperplasia occurs in humans still remains controversial (Abernathy et al., 1994). The controversy concerning human subjects exists primarily due to the limited research methods available to examine living human muscle. Conclusive evidence does exist for animal models mainly because it is possible to directly manipulate the muscle tissue to determine fiber numbers (Abernathy et al., 1994). Animal resistance training protocols do not mimic the training performed by humans. Therefore, one must execute caution in comparing muscle adaptation in animal models to humans (Timson, 1990).
Various non-invasive and invasive measures exist to directly assess muscle hypertrophy in humans. A non-invasive method involves either direct or estimated measurements of the cross-sectional area of the exercised muscle. However, measuring the total volume of the limbs in question can also be useful in examining the extent of hypertrophy. (Carlson, MacDonald, & Payne, 1986). Computed topography scanning or magnetic resonance imaging (MRI) scanning is usually the most common way to take direct measurements of muscle cross-sectional area. These methods use technologically advanced machines that are able to generate an accurate cross-sectional view of the exercised limb. It is then possible to have an accurate measurement of the cross-sectional area while eliminating any possible confounding effects such as connective, bone, and fat tissue. This highly valid and reliable method is one of the most accurate ways that exists to measure muscle growth.
The most common non-invasive, in-direct research methods available involve circumference, volume, and skinfold measurements.. This method is applicable only to limb measurements, as changes in internal body fat content and internal organs are potential sources of measurement error. Mathematical equations do exist to calculate estimated lean muscle cross-sectional area of limbs based on skinfold and circumference data of the examined limb. However, these estimations are not as exact or reliable and therefore challenge the measurement's validity.
In 1986, a study performed by Carlson, MacDonald, and Payne examined the changes in limb volumes of female bodybuilders compared to other non-resistance trained female athletes. Unfortunately, this measurement does not discern fat mass from muscle mass and is therefore not representative of muscle hypertrophy when used by itself. Therefore, one should also include skinfold data and limb circumference measurements for a more comprehensive analysis.
The biopsy technique is the most common invasive method used in human subjects to examine the extent of individual muscle fiber hypertrophy. The biopsy technique involves inserting a large needle-like apparatus into the anaesthetized muscle and removing a very small piece of the actual muscle. Often this is will be repeated in several different places on the same muscle to avoid sampling error. The samples then allow the researcher to view changes in muscle fiber area, identify different muscle fiber types and corresponding cross-sectional area, as well as estimate muscle fiber populations. This technique can be very reliable when there is enough time for recovery between collections (Staron et al., 1992). However, even changes in the depth of the sample often do not account for any potential variation in fiber size, population, or muscle fiber angles (pennation) (Gonyea, Sale, Gonyea, & Mikesky, 1986). This invasive method does not usually occur in animals since sacrificial techniques allow greater manipulation of the muscle and therefore more accurate measurements.
To determine the extent of hyperplasia in living humans, one would usually use a combination of the previously mentioned research techniques. Cadaver studies indicate that differences do exist in fiber number between individuals (Sjöstrom, Lexell, Eriksson, & Taylor, 1991; Lexell, Henriksson-Larsen & Sjöstrom, 1983; Etemadi & Husseini, 1968). Nonetheless, the issue persists that these differences may be due to a strong genetic component and not necessarily training history. By calculating mean fiber area and relating this value to the cross-sectional area of the muscle, it is then possible to estimate the number of fibers per muscle. However, significant errors can occur in estimating muscle fiber numbers since large variations in muscle fiber size and maturity exist in skeletal muscles.
Two studies by Tesch and Larsson and MacDougall, Sale, and Elder both done in 1982 are examples of comparing muscle fiber size to limb girth. The results indicated that although bodybuilders had significantly larger limb girths than control subjects, fiber area was not significantly different. These findings would support the notion of an increase in muscle fiber populations among the bodybuilders used in the study compared to the control groups.
Yet another indirect technique for estimating the extent of hyperplasia is using single fiber electromyography to determine the number of fibers per motor unit (see Larsson & Tesch, 1986). The technique itself can be reliable providing that the insertion of the electrode into the muscle’s motor unit is exact. Otherwise, additional electrical signals from adjacent motor units may confound the result.
Many different training methods exist that result in muscle fiber hypertrophy and hyperplasia. Studies that use live animals as subjects invoke hypertrophy through several different protocols. These protocols vary from surgical removal of synergist muscles, resistance training through behaviour training, electrical stimulation, or various weighted limb techniques. Muscle tissue samples in laboratories that undergo stretch, electrically stimulation, or a combination of both procedures have all shown signs of hypertrophy.
Studies that use exercise routines to cause hypertrophy or hyperplasia usually involve training 2 to 3 times a week for several weeks to months. These studies primarily use untrained subjects and incorporate either isokinetic, isotonic, isometric, concentric, eccentric, or a variety of these types of contractions. The total workload for the exercise session varies from 60 to 120 total repetitions per muscle group. Workload intensity can be as low as 50% or more of the maximal amount of weight the subjects can lift to greater than 100% of their maximum lift. The latter intensity would be typical in training studies that involved intense eccentric contractions.
CELLULAR ACTIVITY ASSOCIATED WITH HYPERTROPHY AND HYPERPLASIA
The cellular adaptation that takes place within the muscle cell appears to be dependent on the type of work it performs (Booth & Merrison, 1986). Muscle hypertrophy from resistance training occurs as the muscle adapts to the exercise to better tolerate the increase in workload. As a result, the muscle fibers become structurally stronger and are able to generate higher levels of force. These effects are due to increases in contractile proteins and connective tissue. A larger cross-sectional area also reduces cellular tension levels on the contracting muscle fiber resulting in a stronger muscle fiber. As a result of this adaptation, the increased size of the fiber can now handle greater tension levels resulting in less structural damage.
The adaptation response of increased structural integrity is not always a result of increases in fiber area. One research study found that after the subjects performed one exercise bout containing only eccentric (lowering the weight) contractions; they were less likely to have as much muscle soreness and damage. This adaptation continued for up to 6 weeks following the exercise compared to the control subjects (Nosaka, Clarkson, McGuiggin, & Byrne, 1991). Obviously, muscle fiber hypertrophy would not account for this adaptation since they only performed the exercise one time. Therefore, there must also be additional cellular and environmental factors that contribute to this phenomenon (Ebbeling & Clarkson, 1989).
Muscle fiber hypertrophy does not occur to the same extent in all muscle fibers. When training for a short period, standard resistance training methods appear to cause greater fast twitch (FT) fiber hypertrophy compared to slow twitch (ST) fiber hypertrophy (Dons, Bollerup, Bonde-Petersen, & Hancke, 1979; Staron et al., 1989; Tesch, 1988). Furthermore, research studies have also shown that eccentric exercise performed by humans' results in a greater disruption of FT fibers than ST fibers (Fridén, Sjöstrom, & Ekblom, 1983; Fridén, Seger, & Ekblom, 1988). This preferential disruption effect may be due to the contractile properties of the proteins that make up ST and FT fibers. The main contractile proteins (myosin heavy chain proteins or MHC proteins) that make up ST fibers do not generate forces that are as strong as the MHC proteins in FT fibers (Bottinelli, Sandoli, Canepari, & Reggiani, 1992). The decreases in force production in ST fibers could also be the reason there is less muscle fiber damage in ST fibers compared to FT fibers when subjected to similar workloads. ST fibers may also be structurally stronger due to greater levels of connective tissue and other adaptations than the larger FT fibers. This difference would result in less muscle fiber damage and disruption for ST fibers compared to FT fibers.
Muscle fiber hypertrophy occurs as a result of changes in protein synthesis and protein degradation rates (Houston, 1986; Schimke, 1975). In other words, protein synthesis rates must out-weigh degradation rates in order for the cell to enlarge (Goldspink, Garlick, & McNurlen, 1983). The result of muscle hypertrophy is an increase in the myofibillar protein content of the muscle fibers (MacDougall et al., 1979). Myofibrils are bundles of the contractile protein filaments contained within the muscle fiber. A discussion of the cellular processes of both protein degradation and protein synthesis follows.
Protein degradation results in a breakdown of contractile proteins and other cellular structures and organelles within the muscle fiber. This can happen as a result of exercise-induced damage, certain muscular diseases, and/or changes in activity pattern (for example, disuse results in muscle fibers shrinking or atrophy). Control of the rate of degradation is mainly a result of proteolytic enzymes (proteases) contained within the cell. These enzymes function to provide energy to the cell as ATP and other intermediates to vital cellular structures (Vander et al., 1990). Proteolytic enzymes also increase protein turn-over to accommodate cellular repair processes (Poortsman, 1981). Cell organelles called lysosomes also have a strong influence on protein degradation rates. These lysosomes will typically become active when the muscle fiber becomes damaged (for example by exercise). The role of lysosomes is to transport the disrupted proteins out of the cell to facilitate the repair process. It is important to note that although protein degradation and synthesis are continually taking place throughout the muscle cell’s life cycle, changes in activity patterns are one of the main stimuli that controls these rates.
Resistance training appears to either decrease cellular degradation rates (Booth, Nicholson, & Watson, 1982) or to result in no changes at all (McNeely, 1994). However, true measurements of protein degradation in live animals and humans are quite difficult to determine. Mainly because the muscle cell will re-utilize degraded proteins that will alter the perceived degradation rate (Booth et al., 1982). Nevertheless, it is quite evident that resistance training does not appear to result in the popular conception that the muscle undergoes an increase in protein degradation rates (Booth et al, 1982; McNeely, 1994).
As previously mentioned, muscle cells are constantly undergoing different rates of protein synthesis and degradation throughout their life cycle as a result of changes in activity patterns. An increase in the rate of protein synthesis above maintenance levels occurs in the muscle cells during periods of linear growth and exercise from birth to adulthood (Borer, 1994; Booth & Morrison, 1986). In the following section, the exercise stimulus in question will be resistance training. This net increase in protein synthesis as a result of exercise ultimately expresses itself as an increase in cross-sectional area of the muscle fibers and eventually, the whole muscle.
Protein synthesis (as well as protein degradation) either decreases or remains the same during and up to 2 hours following the an exercise bout (Booth et al., 1982; Tarnopolsky et al., 1991). Bylund-Fellenius and colleagues (1984) suggest that this effect could be a result of a decrease in the exercised muscles’ ATP. Protein synthesis begins to significantly increase after 4 hours following strength training (Chesley, MacDougall, Tarnopolsky, Atkinson, & Smith, 1992), and can stay elevated for as long as 24 to 41 hours (Tarnopolsky et al, 1992; Wong & Booth, 1990). Generally, routines that result in greater muscle damage will result in elevated protein synthesis rates for a longer time due to the necessary repair.
Interestingly, highly trained, steroid-free bodybuilders showed less of a need for dietary protein than those who were beginning a bodybuilding-type training regime (Tarnopolsky et al., 1992). This may indicate that protein synthesis rates are greater in those who have not developed an adaptation (for example, increased muscle size) to resistance training. Exercise protocols that result in muscle damage often show increases in protein content of the sarcoplasmic proteins (proteins that help keep all the contractile proteins together in a myofibril). This protein increase allows the muscle fiber to tolerate more intensive exercise routines (Poortsman, 1981).
Significant increases in absolute myofibrillar protein amounts do occur as a result of hypertrophy (Lüthi et al. 1986). However, no significant changes occur when expressing increases in protein content as a ratio in proportion to the size of cell (termed myofibrillar density) (MacDougall et al. 1979). This result is most likely due to increases in cellular structures other than myofibrillar protein allowing density to remain unchanged. However, when one relates the concentration of mitochondria to the amount of muscle fiber hypertrophy that occurred, there is a decrease in mitochondrial density (MacDougall et al. 1979). This decrease is either due to the increase of contractile protein, increased degradation of mitochondrial proteins, or a combination of both (MacDougall et al. 1979).
Hyperplasia and Fiber Types
Hyperplasia is an increase in the number of muscle fibers in a muscle. As previously mentioned, hyperplasia is difficult to determine in humans due to the lack of valid and conclusive methodology. Research involving animals has strongly supported the notion that hyperplasia can and does occur in exercise stressed muscles (Gonyea, Ericson, & Bonde-Petersen, 1977; Ho et al. 1980). There is also documentation that suggests evidence of hyperplasia in athletes who have been resistance trained for an extended time (several years at least) (Larssen & Tesch, 1986, 1982; Sjöstrom et al., 1991; Lexell et al., 1983; Etemadi & Husseini, 1968; Nygaard & Nielsen 1978; Tesch & Karlsson 1983, 1985; MacDougall et a., 1982). In contrast, several studies and articles do not support the idea that hyperplasia occurs to any extent in humans (MacDougall, Sale, Alway, & Sutton, 1984; Haggmark, Jansson, & Svane, 1978) or that a difference exists between males and females (Miller, MacDougall, Tarnopolsky, & Sale, 1993). The latter study contradicts a study done in 1987 by Sale and colleagues that showed a significant increase in fiber numbers for males in comparison to females. Therefore, one can see that much controversy still exists whether hyperplasia occurs in humans. It is possible that many experiments found no difference in skeletal muscle fiber numbers between groups due to problems associated with the methodology used in the studies (Abernathy et al., 1994).
Although the debate is still on as to whether or not hyperplasia occurs as a result of chronic resistance training, shifts in the number of certain fiber types do definitely occur in animals (Oakley & Gollnick, 1985; Yarasheki, Lemon, & Gilloteaux, 1990) and humans (Lovind-Anderson, Klitgaard, Bangsbo, & Saltin, 1991; Colliander & Tesch, 1990; Karapondo, Staron & Hagerman, 1991; Staron et al., 1991). These shifts in fiber type appear to occur as a result of changes in the protein content of the muscle fibers. A discussion of the mechanisms that regulate hypertrophy, hyperplasia, and shifts in fiber type as a result of resistance training will occur in the following section.
CELLULAR MECHANISMS INVOLVED IN THE STIMULUS OF HYPERTROPHY AND HYPERPLASIA
The process of muscle hypertrophy and hyperplasia involves many sequenced cellular events. These events ultimately lead to increases in protein synthesis rates, altered protein degradation rates, and increases in muscle fiber numbers. Changes in intra-cellular and extra-cellular activity, specific hormones, receptor sensitivity, and work load can all effect the rate of muscle fiber hypertrophy and hyperplasia. The following section outlines the specific sequence of these events.
Increasing in tension on the muscle fiber through resistance training is one of the main ways to trigger muscle fiber hypertrophy in adults (MacDougall, 1986; Tesch, 1988; Staron et al., 1989). This increase in tension across the muscle fiber most likely results in a disruption of the cellular membrane triggering a cascade of several different reactions. This disruption stimulates the release of specific hormones stored within the membrane of the muscle cell. Fibroblast growth factor (FGF) is a hormone stored in large amounts within the muscle fiber membrane. This factor appears to play a very important role in stimulating the cellular adaptations associated with hypertrophy (Yamada et al., 1989). Disruption of the basal lamina (the cellular membrane that covers the outside of the muscle fiber) may also allow blood borne growth factors (IGF I and II) and hormones (such as testosterone) to bind with the receptors located on the muscle cell membrane (McNeely, 1994).
FGF is a key hormone that activates satellite cells located between the basal lamina and the plasma membrane of the muscle fiber. It is these satellite cells that have a major influence on muscle fiber growth, regeneration, and hyperplasia (White & Esser, 1989). Satellite cells are unique among other cells as they contain a very large nucleus to cytoplasm ratio. This is most likely because it is the material contained within the nucleus that regulates how the muscle fiber grows and repairs itself. Interestingly, these cells do not distribute evenly throughout all muscle fibers or muscle types (Gibson & Schultz, 1982). Oxidative, or slow twitch, muscles typically have greater satellite cell populations compared to glycolytic muscles (fast twitch). Skeletal muscles that undergo use more frequently than other also appear to have increased satellite cell populations (Schultz, 1989). Greater satellite cell numbers in slow twitch muscles are because slow twitch fibers are in use more often during day to day life than fast twitch fibers. Greater frequencies of activation results in constant repair and adaptation processes that go on within the muscle fiber (Schultz, 1989). In conclusion, it appears that the numbers of local satellite cells within the muscle fiber are self-regulated as an adaptation to a high work load stimulus.
Satellite cells are normally not active during normal muscle function (Schultz, 1989) until the muscle fiber experiences an increase in mechanical stress. This mechanical stress translates into cellular disruption for the muscle fiber (in particular protocols that contain eccentric contractions) (White & Esser, 1989; Armstrong, 1984; Darr & Schultz, 1987). Once made active, and provided that the myofiber is not fatally injured, the satellite cells fuse with the muscle fiber and stimulate protein synthesis for repair and/or growth (White & Esser, 1989). Although disruption of the muscle cell may be necessary for muscle fiber hypertrophy, apparently damage to the muscle fiber is not (Bischcoff, 1989).
Muscle fiber damage significantly increases satellite cell activity. This will often cause the satellite cells to migrate to the site of injury on the muscle fiber to stimulate repair processes (White & Esser, 1989). Several hours following the stimulus (Bischoff, 1989), satellite cells and hormones enter the myofiber’s cell cycle to continue to drive the cellular responses associated with hypertrophy and repair (Bischoff, 1989; White & Esser, 1989). Repair processes from minimal damage and subsequent hypertrophy are usually complete following 3-5 days of recuperation (Bischoff, 1989; Schultz, 1989)
Cellular Receptor and Endogenous Hormone Regulation
Cellular receptors are partially responsible for controlling the amount of anabolic and catabolic activity within the muscle cell through a type of ‘lock-and key’ method. In this analogy, the receptor would be the lock and the hormone would act as the key to ‘unlock’ the appropriate cellular response. Anabolic hormones and growth factors bind to receptor sites where their effects initiate such actions as increasing protein synthesis. In this particular case, control of the anabolic process within the cell essentially comes down to the number of available receptors that the muscle cell contains. Increasing the concentration of the hormones in the blood beyond receptor availability would do little to stimulate greater protein synthesis.
Receptor regulation is a complex process. Basically, it comes down to the principle of supply meeting demand. In other words it is the number of available receptors that controls how sensitive the cell will be to a given hormone’s effect. Higher cellular receptor numbers result in greater sensitivity to its respective hormone while lower receptor numbers result in decreased sensitivity. When low levels of a certain hormone continue chronically, an increase or up-regulation of its respective receptors occurs on the cell membrane (Vander, Sherman, & Luciano, 1990). Conversely, when an excess of a particular hormone is present around the muscle cell, a reduction or down-regulation occurs in the numbers of that specific receptor site (Vander et al., 1990). For instance, this latter condition could exist in athletes who continue to use androgenic-anabolic steroids over a long period of time. These changes occur to control how the target cell will react to changes in hormone levels and regulate subsequent growth effects.
Changes in activity level and metabolic demand placed on the muscle fiber appear to have a strong influence on the number of available receptor sites. A study performed by Inoue and colleagues in 1993 showed a rapid increase in androgen receptors after only 5 days of electrical stimulation of the hind limb muscles in the rat. There is also evidence to support the notion that the increase in androgen receptors occurs mostly in glycolytic muscles when exposed to resistance training (Deschenes et al., 1994). This may help to explain why there is greater fast twitch hypertrophy compared to slow twitch hypertrophy in response to a resistance training protocol. However, it is important to note that the increase in androgen hormone receptors does not account for the influence of additional hormones (such as insulin and growth factors) and their specific receptors on protein synthesis. Androgenic hormones can also affect the binding capacity of other hormones on the muscle cell. An example of this is testosterone that may interfere with the binding capacity of catabolic hormones, such as cortisol, resulting in reduced protein degradation rates (Waterlow, Garlick, & Millward, 1978). Presumably, this would result in an increase in the synthesis of contractile proteins with in the muscle fiber.
Circulating levels of anabolic hormones and growth factors partially control receptor regulation and consequently cell sensitivity to hormone levels. Resistance training is known to cause increases in blood levels of testosterone (Kraemer et al., 1991; Weiss, Cureton, & Thompson, 1983), random increases in insulin-like growth factor I (IGF-I) (Kraemer et al., 1991), and stimulate growth hormone release (Kraemer et al., 1991; Kraemer, Kilgore, Kraemer, & Castracane, 1992). Increases in testosterone may exert an influence on recovery during the exercise period possibly due to increases in cellular anabolism. Resultant increases in cellular anabolism during this time may guard against possible intra-cellular damage to the muscle cells by reducing protein degradation rates and increasing protein synthesis rates. However, testosterone returns to baseline levels soon after the exercise stimulus (Kraemer et al., 1991), and constant long-term resistance training may reduce circulating testosterone levels (Arce, De Souza, Pescatello, & Luciano, 1993). One could conclude that although testosterone does have a role in stimulating protein synthesis resulting in muscle hypertrophy, its influence may not be as large as compared to other anabolic hormones and growth factors.
Growth hormone does not appear to have direct roles in stimulating muscle hypertrophy in adult humans (Yarasheski et al., 1992). Growth hormone exerts its influence primarily through stimulating production (Vander et al., 1990) and release of growth factors such as IGF-I (Kelly, Dijane, Postel-Vinay, & Edery, 1991). Contrary to testosterone, stimulated increases of growth factors (such as IGF-I) do not occur until several hours after significant increases in growth hormone levels (Florini, Printz, Vitiello, & Hintz, 1985). Once stimulated, these growth factors can then exert a direct influence on the muscle cell to stimulate protein synthesis. Growth hormone given in small doses throughout the day appears to cause a greater growth effect in exercised muscles in comparison to a single steady dose (Borer, 1994; Hindmarsh et al., 1992). Perhaps the increase of an additional daily secretion of growth hormone caused by resistance training may be partially responsible for the anabolic effect of increased protein synthesis.
Hyperplasia and Shifts in Fiber Type
Increases in muscle fiber population appear to be at least partially regulated by satellite cell activity (White & Esser, 1989). Exercise protocols that result in extreme muscle fiber damage leading to fiber death can make satellite cells active to create the basis of a new muscle fiber (called a myotube) (Carlson & Faulkner, 1983). When a muscle fiber has a fatal injury, the fiber undergoes necrosis (degradation) by both lysosomal activity and phagocytosis. Phagocytosis is a cellular "cleaning" response that results in cellular waste removed from the interior of the cell. While the muscle fiber degrades and cleans itself, satellite cells contained within the muscle membrane increase in numbers (most likely due to exposure of growth factors) and begin to form new myotubes (Schultz, 1989; White & Esser, 1989). It is these myotubes that lead to the formation of a new muscle fiber. Satellite cells act only locally on the muscle cell that supports them. They do not move to other muscle cells or generate new fibers external to their "home-base" unless the cell membrane ruptures. In such a scenario, satellite cells are then able to leave the confines of the muscle fiber. This process may ultimately lead to the creation of new muscle fibers in the spaces between existing muscle cells. Once these new fibers are innervated they are able to contribute to the overall increase in functioning muscle fibers (Kennedy, Eisenberg, Reid, Sweeney, & Zak, 1988).
Another way that hyperplasia may take place is by longitudinal fiber splitting (Tamaki, Uchiyama, & Nakano, 1992). Although the exact mechanism for this cellular effect is not clearly understood, it appears that it is a result of muscle damage either caused by chronically high workload volumes (Larsson & Tesch, 1986) or eccentric contractions (Darr & Schultz, 1987). The effect of hyperplasia, as determined by examining muscle cross-sectional area, may also occur as a result of muscle fiber branching (Reitsma, 1969; Halkjaer-Kristensen & Ingemann-Hansen, 1986). As far as the hormonal effect, a study performed by Alway and Starkweather in 1993 showed that high levels of anabolic-androgenic steroids had no additional effect on muscle fiber hyperplasia in adult quails. Although drawing conclusions as to what transpires in humans is not wise, this study does provide evidence that it is mainly the workload stimulus that is responsible for increasing muscle fiber and not the androgenic hormonal environment.
It is possible that surviving myofibers may generate newly adjoining fibers through a type of cellular branching from a local injury site. As previously mentioned, satellite cells migrate to the damaged area to begin repair processes. From this site, a new muscle fiber could generate off the old muscle fiber as a result of satellite cell activity. This could result in the X, Y, and H- shaped fiber branching patterns seen in some muscle fibers. Although whole new independent muscle fibers may not generate in this fashion, the appearance of new fiber growth and apparent muscle fiber hyperplasia would exist in studies that used estimations based on cross-sectional area measurements of the whole muscle.
Any "new" muscle fibers would contain mostly mature myosin and actin contractile proteins and are detectable by appropriate staining procedures. Upon examination of muscles thought to have undergone hyperplasia, it becomes evident that many of the muscle fibers contain either partial or entirely new (embryonic) and developing contractile proteins (Yamada et al., 1989). Although regulation of hyperplasia can occur by a combination of the mechanisms mentioned above, a certain degree of genetic predisposition may affect muscle fiber numbers as well (Abernathy et al., 1994).
Resistance training appears to affect fiber type populations as well. These shifts in fiber type appear to correspond to the specific type of exercise that the muscle performs (Abernathy et al., 1994). Constant bodybuilding-type training, typically characterized by short rest periods and high work volumes at moderate intensities, seem to result in an increase of slow twitch fibers rather than fast twitch fibers (Tesch & Larsson, 1982). In contrast to this, Olympic and power lifting (which is characterized by long rest periods, lower volumes, higher intensities, and explosive movements) may result in a preferential increase of type IIb fast twitch fibers (muscle fibers that are very fast and have very little aerobic enzymes) over both fast twitch type IIa (muscle fibers that are also fast but have both anaerobic and aerobic enzymes) and slow twitch muscle fibers (type I fibers that are the slowest of all muscle types and contain mainly aerobic enzymes) (Tesch & Larsson, 1982). It is important to note that the studies using only experienced lifters supported this trend and that other factors such as genetic inheritance could also affect the result. In studies that involved baseline and histochemical measurements over weeks and months, fiber shifts from type IIb to type IIa occur in response to resistance training (Colliander & Tesch, 1990; Karapondo et al., 1991; Staron et al., 1991).
Muscle fibers consist of different concentrations of myosin heavy chain proteins. This article only discusses type I, IIa, and IIb myosin heavy chain proteins (Klitgaard, 1990; Staron and Pette, 1987). As the names suggest, slow twitch fibers consist of mainly type I proteins; fast twitch fibers consist mainly of type IIa proteins; and so on. An increase in specific protein content of certain myosin heavy chain proteins along with a decrease in other myosin heavy chain proteins can result in a shift towards a different fiber type. Simply put, less type I MHC proteins and more type IIa proteins results in a shift towards a type IIa fiber. This shift is a result of differing rates of protein synthesis and degradation of the MHC proteins. The changes of protein contraction types are a result of changes in messenger ribosomal nucleic acids of the muscle cell (Periasamy, Gregory, Martin, & Stirewalt, 1989).
FACTORS AFFECTING THE HYPERTROPHIC AND HYPERPLASTIC RESPONSE OF MUSCLE FIBERS
Investigations into the cellular processes associated with hypertrophy have been ongoing by numerous researchers over the years. However, the precise amounts of stimulus that results in the greatest amount of muscle fiber hypertrophy still remains elusive. This is partly because most studies investigating the effects of resistance training on muscle hypertrophy use different resistance training protocols for different periods of times. This makes inter-study comparisons difficult. In addition, the genetic component of muscle fiber numbers and protein synthesis rates can not be overlooked. Considering these facts, this section will attempt to provide a review of past training studies to better understand the workload factors that affect the hypertrophic and hyperplastic response of muscle fibers.
As mentioned in the previous section, tension placed upon the muscle appears to be the main stimulus that results in hypertrophy of the muscle fibers (Goldberg, Etlinger, Goldspink, & Jablecki, 1975). The nature of the cellular responses associated with hypertrophy suggest that muscle growth has a type of adaptive threshold (White & Esser, 1989). In other words, the muscle fiber must exceed a specific workload (based on the fiber’s training history) for the muscle fiber to respond by increasing in cell size. Too small of a workload will not trigger the adaptations associated with hypertrophy. Too great a workload will increase degradation rates and possibly impair muscle fiber enlargement (Ebbeling & Clarkson, 1989). Therefore an examination of the various factors contributing to this specific workload allows us understand the relationship between the amount of tension and the resultant rate of muscle hypertrophy.
Several types of contractions create tension on a muscle fiber. The three main types of contractions covered in this section include isometric, concentric, and eccentric contractions. These movements can also vary in contraction speed. Isokinetic contractions result in a uniform speed throughout the duration of the contraction, whereas isotonic contractions vary in the rate of muscle shortening throughout the movement. To simplify this review, isometric contractions will be included with concentric contractions.
Effects of Contraction Type on Hypertrophy
There is a variety of differing training protocols that are in use to determine the effect of the contraction type on hypertrophy (Abernathy et al., 1994). A significant hypertrophic occurs with the three (concentric, eccentric, and isometric) different types of contractions (Housh, Housh, Johnson, & Chu, 1992; Mayhew, Rothstein, Finucane, & Lamb, 1995; Garfinkel & Cafarelli, 1992). However, due to the variations in the training regimes and the time periods used in the training studies, it is difficult to draw substantial conclusions on the most efficient movement type in stimulating hypertrophy.
Hather, Tesch, Buchanan, and Dudley (1991) examined the effect of combined concentric and eccentric contractions of 4 - 5 sets of 6 - 12 submaximal repetitions. This regime resulted in greater hypertrophy of fast and slow twitch muscle fibers by up to 14% when compared to training volumes that were twice as large but consisted solely of concentric contractions. The latter training routine resulted in no significant hypertrophy in the slow twitch muscle fibers. A study performed by Côté and colleagues (1988) showed no significant hypertrophy as a result of 30 total repetitions, performed 5 times a week, at 65% of maximal strength supports this as well.
Contrary to these studies, significant whole muscle hypertrophy occurred with just concentric contractions. Two such studies had the subjects exercising 3 times a week. These exercise periods consisted of workloads of 50 and 60 total repetitions at 90% of their maximal strength while the other study did not state intensity (Housh et al., 1992; Mayhew et al, 1995). In addition, another training study examined the muscle adaptations between either eccentric or concentric only muscle contractions (Mayhew et al., 1995). The subjects exercised 3 times a week at equal power levels for 50 total repetitions. The results showed significantly greater muscle hypertrophy in the group that performed only concentric movements as opposed to the eccentric only group.
Eccentric contractions cause cellular damage to the muscle fiber and even cellular death in extremely damaged fibers (Ebbeling & Clarkson, 1989). As a result, eccentric contractions result in high satellite cell activity to improve repair processes. Although concentric contractions appear to cause undetectable damage, (Newham, McPhail, Mills, & Edwards, 1983), the contractions most likely activate satellite cells since these cells appear to have essential roles in regulating muscle hypertrophy (Rosenblatt, Yong, & Parry, 1994). Therefore, minimal amounts of disruption necessary to make satellite cells active may occur in the myofiber as a result of concentric contractions (Bischoff, 1989). As a result this reduced disruption is sufficient to result in muscle fiber hypertrophy (Bischoff, 1989).
Considering the above observations, it would be safe to assume that combined eccentric and concentric muscle contractions are more effective at producing greater increases in muscle hypertrophy than either concentric or eccentric contractions alone. It does not appear that eccentric contractions are necessary for fast twitch fiber hypertrophy. However, eccentric contractions may be necessary for slow twitch hypertrophy. It is possible to theorize that changes in muscle membrane tensile force from both types of contractions resulted in an optimal disruption of the muscle membrane. This disruption then stimulated the necessary anabolic processes. Along with tensile force, there appears that there is also a workload volume component in regulating the extent of muscle growth.
The Extent of Muscle Fiber Hypertrophy
Studies investigating the effects from several weeks to several years of resistance training support the idea that muscle fibers may reach a maximal cross-sectional area after only 6 months (Abernathy et al., 1994; MacDougall et al., 1982). One hypothesis proposed by Gonyea (1983) suggests the limits of fiber hypertrophy are a result of increases in the diffusion distance from the capillary bed to the middle of the muscle cell. This would then limit essential components to the necessary cellular structures required for muscle fiber growth.
Another factor that could affect the upper limit of fiber hypertrophy is the result of the cellular adaptation that occurs after several months of resistance training. This at least partially occur in the basal lamina of the myofiber resulting in a stronger membrane, perhaps as a result of eccentric contractions (Ebbeling & Clarkson, 1989). This strengthened membrane would thereby become more difficult to disrupt and trigger the associated growth effects. In this scenario, any future growth after this adaptation would most likely be a result of associated endogenous hormone activity. An illustration of this effect possibly occurs in a study by Kuipers and colleagues (1993). This study showed significant muscle fiber growth in experienced bodybuilders only after administration of anabolic steroids. However, it is conceivable that other factors used in the study including sampling techniques and, in particular, the training regime may have affected the results.
The limit of muscle fiber hypertrophy and the time it takes to reach this limit is very difficult to determine. This is mainly because skeletal muscles contain a variety of different sizes and maturities of muscle fibers. Although average fiber size for fast twitch muscle fibers in untrained individuals range from 3000 to 6000 square micrometers (Staron et al., 1989; Sale, MacDougall, Jacobs & Garner, 1990, Costill, Coyle, Fink, Lesmes, & Witzman, 1979), short term resistance training can increase fiber area to greater than 7000 square micrometers (Costill et al., 1979). Experienced powerlifters and bodybuilders generally have larger fast twitch muscle fibers than those who have been training for only a short time. Average fiber areas of these experienced lifters typically fall around 9000 to 10000 square micrometers (Alway, Grumbt, Stray-Gundersen, & Gonyea, 1992; MacDougall, Sale, Alway, Sutton, 1984; Tesch, Thorsson, & Essén-Gustavsson, 1989). However, there is also evidence that smaller fibers ranging in size from 6000 to 7000 square micrometers do exist in these athletes (Tesch & Larsson, 1982; MacDougall et al., 1982). These large inter-individual variations in muscle fiber size make it difficult to determine if there is a maximal size that muscle fibers might reach. However, it appears that it may still take several years to reach extremely hypertrophied levels associated with elite strength athletes.
Fast twitch muscle fibers generally grow larger and at a greater rate in comparison to slow twitch fibers (Abernathy et al., 1994). Slow twitch fiber hypertrophy often becomes more evident between the 8th and 16th week of training in comparison to the quick growing FT fibers (Hakkinen, Komi, & Tesch, 1981). Slow twitch fibers often tend not to plateau and will continue to enlarge with prolonged resistance training (Staron, Hagerman, & Hikida, 1981; Tesch & Karlsson, 1985). This slower rate of growth in slow twitch fibers is most likely because there is smaller net increases in nuclear material from satellite cell activation compared to FT fibers (Abernathy et al., 1994). The reason for greater growth in fast twitch fibers may be that these fibers are not as structurally strong as slow twitch fibers. This structural difference could be due to lower connective tissue amounts or decreased responsiveness of the cellular structures (Ebbeling & Clarkson, 1989). This decrease in structural integrity would therefore result in a greater disruption from intense training a given workload (Fridén et al., 1983). This low threshold for disruption may make fast twitch fibers more susceptible to engaging the hypertrophic processes in comparison to slow twitch fibers.
Workload and Hypertrophy
Research examining workload on muscle hypertrophy is continuing to grow at an ever increasing rate. Unfortunately, many of these studies use a variety of different workload volumes and exercise protocols. This results in making direct comparisons and drawing strong conclusions based on the results difficult, if not impossible. Nevertheless, certain trends do emerge when one looks at workload volume and recovery time.
Higher volume training (Sale et al., 1990; MacDougall et al., 1979) does not seem to be the best way to trigger efficient muscle growth in comparison to lower volume modes. Greater fiber hypertrophy occurs when training protocols use 30 - 40 repetitions per muscle group performed at an intensity of 75%-85% of maximal strength (Kuno, Katsuto, Akisada, Anno, & Matsumoto, 1990; Staron et al., 1989). Lower intensities (below 60%) and lower volumes do not result in as much, if any, significant muscle hypertrophy (Dons et al., 1979; Lüthi et al., 1986). Exercise performed at higher intensities with similar volumes also do not cause much muscle growth (Ratzin Jackson, Dickinson, & Ringel, 1990). In fact, experienced bodybuilders did not show significant muscle hypertrophy when they were following a typical high volume training routine (Alway et al., 1992). In comparison, those who begin resistance training do show significant hypertrophy following such a regime. This would suggest that a potential muscular adaptation to the stress of high volume weight training may occur.
Increases in fiber number appear to be a result of chronic training with high workloads (Abernathy, 1994). Athletes, such as bodybuilders, typically train with moderate weights but use very high workload volumes. They also show greater fiber numbers than untrained or trained individuals who use lower volumes (Abernathy, 1994, Tesch & Larsson, 1986). This could indicate a possible relationship between higher workload volumes and a hyperplastic response of muscle to this type of training. Theoretically, this seems plausible considering the relationship between high workload volumes and muscle damage (Ebbeling & Clarkson, 1989) that result in possible neogenesis or branching of muscle fibers. In addition, it appears that a certain amount of muscle fiber hypertrophy must be in place before hyperplasia occurs (Antonio & Gonyea, 1993).
Eccentric contractions may not be necessary to cause increases in muscle fiber number, as suggested by Abernethy and colleagues (1994). Studies performed on swimmers, kayakers, and wheelchair athletes show potential evidence of hyperplasia in the exercised muscle groups (Nygaard & Nielsen, 1978; Tesch & Karlsson, 1983, 1985). The movements in these sports are predominately concentric in nature, with very minimal forceful eccentric contractions, yet they still show greater fiber numbers. This lends strong support to the idea that it is the amount of work a muscle does against a given resistance that leads to hyperplasia, and not necessarily the total volume of eccentric contractions performed
Recovery and Hypertrophy
The time periods associated with net increases in contractile proteins vary depending on the amount of stress placed upon the muscle fiber. Muscle fibers exposed to high workloads; especially those that contain intense eccentric contractions; undergo high amounts of damage and can require up to 14 days (and sometimes longer) to recover (Armstrong, 1986). Those muscle fibers that do not experience extensive damage return to normal cellular activity after 3-5 days, as evidenced by the stabilization of satellite cell activity (Schultz, 1989). The muscle fiber must first repair all damage to increase its protein content by increasing protein synthesis. This will cause the fiber to grow larger and guard against any future damage to it. Accordingly, maximal rates of hypertrophy could occur by stimulating the muscle fiber through resistance causing minimal cellular disruption every 3 - 5 days.
FACTORS AFFECTING WHOLE MUSCLE GROWTH
Increases in whole muscle cross-sectional is primarily due to increases in muscle fiber area, fiber number, and increases in the amounts of other tissues that make up the muscle. An increase in muscle fiber area is the main drive towards increase in whole muscle cross-sectional area (MacDougall, 1984). Other factors that regulate muscle cross-sectional area are changes in energy substrate stores (such as glycogen and fat content), changes in cellular fluid content, and increases in connective tissues and other non-contractile tissues.
High muscle fiber numbers occur in hypertrophied muscles moreover have a contribution to the overall size of the muscle. However, the contribution of increased fiber number to muscle hypertrophy does not appear to be as great as one may assume. Hyperplasia only begins to contribute to muscle mass after several years of prolonged and intensive resistance training (Larsson & Tesch, 1986). Even after hyperplasia has occurred, the effect of increased fiber numbers on whole muscle cross-sectional area appears to be minimal (Appel, 1990). Although evidence of high muscle fiber populations usually occurs in extremely hypertrophied muscle, the high fiber numbers could be a result of the training regime or due to a predetermined genetic predisposition (Abernathy et al., 1994). Current evidence supports the notion that hyperplasia could contribute to whole muscle cross-sectional area through constant resistance-type training.
Non-contractile tissues and extracellular fluid content that is within a muscle can also affect muscle area. Connective tissues hold the muscle fibers together and give them a base upon which to contract, recover, and grow larger (Fritz & Stauber, 1988). Resistance training can increase the absolute amounts of connective tissue in the exercised muscle (Viidik, 1986) and therefore contribute to increases in muscle mass. Conceivably, differences in bone mass between individuals could also play a role in muscular girths, giving the impression of greater amounts of muscular development.
Increases in extra-cellular fluid and inflammation occur with more intense forms of resistance training as a result of increases in cellular damage (Ebbeling & Clarkson, 1989). Such increases in fluids can cause swelling and therefore also result in a temporary increase in whole muscle cross-sectional area. In addition, energy substrate storage sites around and inside the muscle could also affect muscular girths. Increases in the amounts of glycogen and lipids stored in the muscle can occur with training (Fox et al., 1993) and may also contribute to increases in overall muscle mass.
Resistance training affects whole muscle cross-sectional area mainly through hypertrophic and hyperplastic effects of the muscle fibers. Increases in substrate storage sites, connective tissue, adipose (fat) tissue and fluid content can also affect muscle size. Hypertrophy increases the contractile protein content of the muscle fibers by rising protein synthesis and depressing degradation rates so that the fiber can better handle greater workloads. Fast twitch fibers appear to grow larger and at a greater rate than slow twitch fibers that typically do not show increases in cross-sectional area until after many weeks of resistance training.
Muscle fiber hypertrophy results from an increase in workload that exceeds a type of structural threshold of the muscle fiber. The activity that the muscles perform determines this threshold. The exercise results in the disruption of the basal lamina and other cellular constituents of the muscle cell triggering a cascade of cellular actions. The disruption releases growth factors that stimulate satellite cells to merge with the muscle fiber to stimulate protein synthesis. Once satellite cells have triggered the growth response, other endogenous hormones contribute to this anabolic effect through their interaction with specific cellular receptors.
The amount of workload necessary to stimulate hypertrophy appears to occur as a result of the specific training history of that muscle. Unfortunately, specific guidelines based on these factors to increase muscle size still remain elusive. However, resistance training protocols that incorporate both concentric and eccentric muscular contractions seem to cause the greatest effect. Thirty to fifty repetitions performed every 3 - 5 days at an intensity of 75%-85% of maximal strength appear to result in greater growth than other resistance training protocols that use higher or lower total work load volumes.
A large amount of evidence supports the notion that hyperplasia occurs in humans. Significant differences in muscle fiber populations occur in chronically resistance trained athletes in comparison to either untrained or short term (several months) trained subjects. The main stimulus for hyperplasia appears to be a combination of satellite cell activity and longitudinal fiber splitting. Such cellular responses most likely result from a combination of long-term resistance training, large workload volumes, and extensive muscle fiber damage. Although increases in muscle fiber numbers can increase muscle cross-sectional area, its effect on gross muscle hypertrophy appears to be minimal in comparison to that of muscle fiber hypertrophy.
Abernathy, P.J., Jürimäe, J., Logan, P.A., Taylor, A.W., & Thayer, R.E. (1994). Acute and Chronic Response of Skeletal Muscle to Resistance Exercise. Sports Medicine. 17 (1), 22-38.
Alway, S.E., Gonyea, W.J., & Davis, M.E. (1990). Muscle Fiber Formation and Fiber Hypertrophy During the Onset of Stretch-Overload. American Journal of Physiology 259 (Cell Physiology, 28), C92-C102.
Alway, S.E., Grumbt, W.H., Stray-Gundersen, J., Gonyea, W.J. (1992). Effects of Resistance Training on Elbow Flexors of Highly Competitive Bodybuilders. Journal of Applied Physiology. 72 (4), 1512-1521.
Alway, S.E., MacDougall, J.D., Sale, D.G., Sutton, J.R., & McComas, A.J. (1986). Functional and Structural Adaptations in Skeletal Muscle of Trained Athletes. Journal of Applied Physiology. 64 (3), 1114-1120.
Antonio, J., & Gonyea, W.J. (1993). Progressive Stretch Overload of Skeletal Muscle Results in Hypertrophy before Hyperplasia. Journal of Applied Physiology. 75 (3), 1263-1271.
Arce, J.C., De Souza, M.J., Pescatello, L.S., & Luciano, A.A. (1993). Subclinical Alterations in Hormone and Semen Profile in Athletes. Fertility & Sterility. 59 (2),398-404.
Armstrong, R.B. (1984). Mechanisms of Exercise-Induced Soreness Delayed Onset Muscle Soreness: A Brief Review. Medicine and Science in Sports and Exercise. 16, 529-538.
Armstrong, R.B. (1986). Muscle Damage and Endurance Events. Sports Medicine. 3, 370-381.
Bischoff, R. (1989). Analysis of Muscle Regeneration Using Single Myofibers in Culture. Medicine and Science in Sports and Exercise. 21 (5), S164-S172
Booth, F.W., & Morrison, P.R. (1986). Control of Protein Synthesis in Muscle With Special Reference to Exercise. In B. Saltin (Ed.), Biochemistry of Exercise VI (pp. 49-62). Champaign, Illinois: Human Kinetics Publishers.
Booth, F.W., Nicholson, W.F., & Watson, P.A. (1982). Influence of Muscle Use on Protein Synthesis and Degradation. Exercise and Sport Science Reviews. 10, 27-48.
Borer, K.T. (1994). Neurohumoral Mediation of Exercise-Induced Growth. Medicine and Science in Sports and Exercise. 26 (6), 741-754.
Bottinelli, R., Sandoli, D., Canepari, M., & Reggiani, C. (1992). Maximal Isometric Force and Myosin Heavy Chain Composition in Single Skinned Skeletal Muscle Fibers from the Rat. Pflugers Archives - European Journal of Physiology. 420, r193.
Bylund-Fellenius, A.C., Ojama, K.M., Flaim, K.E., Li, J.B., Wassner, S.J., & Jefferson, L.S. (1984). Protein Synthesis Versus Energy State in Contracting Muscles of Perfused Rat Hindlimb. American Journal of Physiology. 246, E297-E305.
Carlson, B.M., & Faulkner, J.A. (1983). The Regeneration of Skeletal Muscle Fibers Following Injury: A Review. Medicine and Science in Sports and Exercise. 15, 187-198.
Carlson, J.S., MacDonald, W.A., & Payne, W.R. (1986). The Female Bodybuilder: A Morphological, Cardiorespiratory and Strength Performance Comparison with Non-Weight Trained Female Athletes. The Australian Journal of Science and Medicine and Sport 20 (1), 7-11.
Chesley, A., MacDougall, J.D., & Tarnopolsky, M.A., Atkinson, S.A., & Smith, K. (1992). Changes in Human Muscle Protein Synthesis After Resistance Exercise. Journal of Applied Physiology. 73 (4), 1383-1388.
Colliander, E.B., & Tesch, P.A. (1990). Effects of Eccentric and Concentric Muscle Actions in Resistance Training. Acta Physiologica Scandinavica. 140, 31-39.
Costill, D.L., Coyle, E.F., Fink, W.F., Lesmes, G.R., & Witzman, F.A. (1979). Adaptations in Skeletal Muscle following Strength Training. Journal of Applied Physiology. 46 (1), 96-99.
Czerwinski, S.M., Novakofski, J., Bechtel, P.J. (1993). Modulation of IGF mRNA Abundance During Muscle Denervation Atrophy. Medicine and Science in Sports and Exercise. 25 (9), 1005-1008.
Darr, K.C., & Schultz, E. (1987). Exercise-Induced Satellite Cell Activation in Growing and Mature Skeletal Muscle. Journal of Applied Physiology. 63, 1816-1821.
Deschenes, M.R., Maresh, C.M., Armstrong, L.E., Covault, J., Kraemer, W.J., & Crivello, J.F. (1994). Endurance and Resistance Exercise Induce Muscle Fiber Type Specific Responses in Androgen Binding Capacity. Journal of Steroid Biochemistry and Molecular Biology. 50 (3/4), 175-179.
Dons, B., Bollerup, K., Bonde-Petersen, F., & Hancke, S. (1979). The Effect of Weight-Lifting Exercise Related to Muscle Fiber Composition and Muscle Cross-Sectional Area in Humans. European Journal of Applied Physiology and Occupational Physiology. 40, 95-106.
Ebbeling, C.B., & Clarkson, P.M. (1989). Exercise Induced Muscle Damage and Adaptation. Sports Medicine. 7, 207-234.
Etemadi, A.A., & Husseini, F. (1968) Frequency and Size of Muscle Fibers in Athletic Body Builders. Anatomical Record. 162, 269-274.
Florini, J.R., Printz, P.N., Vitiello, M.V., & Hintz, R.L. (1985). Somatomedin-C Levels in Healthy Young and Old Men: Relationship to Peak and 24 hour Integrated Levels of Growth Hormone. Journal of Gerontology. 40, 2-7.
Fridén, J., Seger, J., & Ekblom, B. (1988). Sublethal Muscle Fiber Injuries After High-Tension Anaerobic Exercise. European Journal of Applied Physiology and Occupational Physiology. 57, 360-368.
Fridén, J., Sjöstrom, M., Ekblom, B. (1983). Myofibrillar Damage Following Intense Eccentric Exercise in Man. International Journal of Sports Medicine. 4, 170-176.
Fritz, V.K., & Stauber, W.T. (1988). Characterization of Muscles Injured by Forced Lengthening. II. Proteoglycans. Medicine and Science in Sports and Exercise. 20, 354-361.
Garfinkel, S., & Cafarelli, E. (1992). Relative Changes in Maximal Force, EMG, and Muscle Cross-Sectional Area after Isometric Training. Medicine and Science in Sports and Exercise. 24 (11), 1220-1227.
Gibson, M.C., & Schultz, E. (1982). The Distribution of Satellite Cells and Their Relationship to Specific Fiber Types in the Soleus and Extensor Digitorum Longus Muscles. Anatomical Record. 202, 329-337.
Goldberg, A.L., Etlinger, J.D., Goldspink, D.F., & Jablecki, C. (1975). Mechanisms of Work Induced Hypertrophy of Skeletal Muscle. Medicine and Science in Sports and Exercise. 7 (3), 185-198.
Goldspink, D.F., Garlick, P.J., & McNurlan, M.A. (1983). Protein Turnover Measured In Vivo and In Vitro Muscles Undergoing Compensatory Growth and Subsequent Denervation Atrophy. Biochemistry Journal. 210, 89-98.
Gonyea, W.J. (1983). Skeletal Muscle Growth Induced by Strength Training. In D. Edington and T. White (Eds.), Frontiers of Exercise Biology. Champaign, Illinois: Human Kinetics Publishers.
Gonyea, W.J., Ericson, G.C., & Bonde-Petersen, F. (1977). Skeletal Muscle Fiber Splitting in Induced by Weight-Lifting Exercise in Cats. Acta Physiologica Scandinavica. 99, 105-109.
Gonyea, W.J., Sale, D.G., Gonyea, F.B., & Mikesky, A. (1986). Exercise Induced Increases in Muscle Fiber Number. European Journal of Applied Physiology and Occupational Physiology. 55, 137-141.
Hakkinen, K., Komi, P.V., & Tesch, P.A. (1981). Effect of Combined Concentric and Eccentric Strength Training and Detraining on Force-Time, Muscle Fibre, and Metabolic Characteristics of Leg Extensor Muscles. Scandinavian Journal of Sports Sciences. 3, 50-58.
Halkjaer-Kristensen, J., Ingeman-Hansen, T. (1986) Discussion From The Session: Wasting and Growth of Skeletal Muscle. In B. Saltin (Ed.), Biochemistry of Exercise VI (pp. 563-566). Champaign, Illinois: Human Kinetics Publishers.
Hather, B.M., Tesch, P.A., Buchanan, P., & Dudley, G.A. (1991). Influence of Eccentric Actions on Skeletal Muscle Adaptations to Resistance Training. Acta Physiologica Scandinavica. 143 (2), 177-185.
Hindmarsh, P.C., Mathews, D.R., Straton, I, Pringle, T.V., & Brook, C.G.D. (1992). Rate of Change (Modulation) of Serum Growth Hormone Concentrations is a More Important Factor in Determining Growth Rate than Duration of Response. Clinical Endocrinology. 36, 165-170.
Ho, K.W., Roy, R.R., Tweedle, C.D., Heusner, W.W., Van Huss, W.D., et al. (1980). Skeletal Muscle Fiber Splitting with Weight Lifting Exercise in Rats. American Journal of Anatomy. 157, 433-440.
Housh, D.J., Housh, T.J., Johnson, G.O., & Chu W. (1992). Hypertrophic Response to Unilateral Concentric Isokinetic Resistance Training. Journal of Applied Physiology 73 (1), 65-70.
Houston, M. (1986). Adaptations in Skeletal Muscle to Training and Detraining: The Role of Protein Synthesis and Degradation. In B. Saltin (Ed.), Biochemistry of Exercise VI (pp. 63-74). Champaign, Illinois: Human Kinetics Publishers.
Inoue, K., Yamaski, S., Fushiki, T., Kano, T., Moritani, T., Itoh, K., & Sugimoto, E. (1993). Rapid Increase in the Number of Androgen Receptors Following Electrical Stimulation of the Rat Muscle. European Journal of Applied Physiology and Occupational Physiology. 66, 134-140.
Karapondo, D., Staron, R., Hagerman, F. (1991). The Time Course for Fast-Twitch Fiber Type Conversions in Resistance Trained Men and Women. Medicine and Science in Sports and Exercise. 23, S130.
Katch, V.L., Katch, F.I., Moffat, R., & Gittleson, M. (1980) Muscular Development and Lean Body Weight in Body Builders and Weight Lifters. Medicine and Science in Sports and Exercise. 12, 340-344.
Kelly, P.A., Dijane, J., Postel-Vinay, M., & Edery, M. (1991). The Prolactin/Growth Hormone Receptor Family. Endocrine Review. 12, 235-251.
Kennedy, J.M., Eisenberg, B.R., Reid, S.K. (1988). Nascent Muscle Fiber Appearance in Overloaded Chicken Slow-Tonic Muscle. American Journal of Anatomy. 181, 203-215.
Klitgaard, H., Zhou, M., Schiaffino, S., Betto, R., Salviato G., et al. (1990). Aging Alters the Myosin Heavy Chain Composition of Single from Human Skeletal Muscle. Acta Physiologica Scandinavica. 140, 55-62.
Kraemer, W.J., Gordon, S.E., Fleck, S.J., Marchitelli, L.J., Mello, R., Dziados, J.E., Friedl, K., Harman, E., Maresh, C., & Fry, A.C. (1991). Endogenous Anabolic Hormonal and Growth Factor Responses to Heavy Resistance Exercise in Males and Females. International Journal of Sports Medicine. 12, 228-235.
Kraemer, W.J., Kilgore, J.L., Kraemer, G.R., & Castracane, V.D. (1992). Growth Hormone, IGF-I, and Testosterone Responses to Resistive Exercise. Medicine and Science in Sports and Exercise. 24 (12), 1346-1352.
Kuipers, H., Peeze-Binkhorst, F.M., Hartgens F., Wijnen, J.A., & Keizer, H.A. (1993). Muscle Ultrastructure After Strength Training With Placebo or Anabolic Steroid. Canadian Journal of Applied Physiology. 18 (2), 189-196.HH HH
Larsson, L. & Tesch, P.A.. (1986). Motor Unit Fiber Density in Extremely Hypertrophied Skeletal Muscles in Man. European Journal of Applied Physiology 55, 130-136.
Lexell, J., Henriksson-Larsen, K., Sjöstrom, M. (1983). Distribution of Different Fiber Types in Human Skeletal Muscles. Acta Physiologica Scandinavica 117, 115-122.
Lovind-Andersen, J., Klitgaard, H., Bangsbo, J. & Saltin, B. (1991). Myosin Heavy Chain Expression in Human Skeletal Muscle of Elite Soccer Players: Effect of Strength Training. Acta Physiologica Scandinavica. 143, 24a.
Lüthi, J.M., Howald, H., Claassen, H., Rösler, K., Vock, P., Hoppeler, H. (1986) Structural Changes in Skeletal Muscle Tissue with Heavy-Resistance Exercise. International Journal of Sports Medicine. 7 (3), 123-127.
MacDougall, J.D., Sale, D.G., Alway, S.E., & Sutton, J.R. (1984). Muscle Fiber Number in Biceps Brachii in Bodybuilders and Control Subjects. Journal of Applied Physiology: Respiration, Environment, and Exercise Physiology. 57 (5), 1399-1403.
MacDougall, J.D., Sale, D.G., Elder, G.C.B., & Sutton, J.R. (1982). Muscle Ultrastructural Characteristics of Elite Powerlifters and Bodybuilders. European Journal of Applied Physiology and Occupational Physiology. 48, 117-126.
MacDougall, J.D., Sale, D.G., Moroz, J.R., Elder, G.C., Sutton, J.R., & Howald, H. (1979). Mitochondrial Volume Density in Human Skeletal Muscle Following Heavy Resistance Training. Medicine and Science in Sports and Exercise. 11 (2), 164-166.
Mayhew, T.P., Rothstein, J.M., Finucane, S.D. & Lamb, R.L. (1995). Muscular Adaptation to Concentric and Eccentric Exercise at Equal Power Levels. Medicine and Science in Sports and Exercise. 27 (6), 868-873.
McNeely, E. (1994). The Effects of Selected Exercise Intensities on Skeletal Muscle Protein Degradation. Master of Science Thesis in Kinanthropology submitted to the University of Ottawa, 1-74.
Miller, A.E.J., MacDougall, J.D., Tarnopolsky, M.A., & Sale, D.G. (1993). Gender Differences in Strength and Muscle Fiber Characteristics. European Journal of Applied Physiology and Occupational Physiology. 66, 254-262.
Morrissey, M.C., Harman E.A., Johnson, M.J. (1995). Resistance Training Modes: Specificity and Effectiveness. Medicine and Science in Sports and Exercise. 27 (5), 648-660.
Newham, D.J., Jones, D.A., & Clarkson, P.M. (1987). Repeated High-Force Eccentric Exercise: Effects on Muscle Pain and Damage. Journal of Applied Physiology. 63 (4), 1381-1386.
Nosaka, K., Clarkson, P.M., McGuiggin, M.E., & Byrne, J.M. (1991). Time Course of Muscle Adaptation after High Force Eccentric Exercise. European Journal of Applied Physiology and Occupational Physiology. 63, 70-76.
Periasamy, M., Gregory, P., Martin, B.J., & Stirewalt, W.S. (1989). Regulation of Myosin Heavy Chain Gene Expression During Skeletal Muscle Hypertrophy. Biochemical Journal. 257, 691-698.
Poortsman, J. (1981). Protein Metabolism: Effects of Exercise and Training. Medicine and Sport. 13, 66-76.
Ratzin Jackson, C.G., Dickinson, A.L., & Ringel, S.P. (1990). Skeletal Muscle Fiber Area Alterations in Two Opposing Modes of Resistance-Exercise in the Same Individual. European Journal of Applied Physiology and Occupational Physiology. 61, 37-41.
Rosenblatt, J.D., Yong D., & Parry D.J. (1994). Satellite Cell Activity is Required for Hypertrophy of Overloaded Adult Rat Muscle. Muscle & Nerve. 17 (6),608-613
Sale, D.G., MacDougall, J.D., Alway, S.E., & Sutton, J.R. (1987). Voluntary Strength and Muscle Characteristics in Untrained Men and Women and Male Bodybuilders. Journal of Applied Physiology. 62 (5), 1786-1793.
Sale, D.G., MacDougall, J.D., Jacobs, I., & Garner, S. (1990). Interaction Between Concurrent Strength and Endurance Training. Journal of Applied Physiology. 68 (1), 260-270.
Schimke, R.T. (1975). Methods for Analysis of Enzyme Synthesis and Degradation in Animal Tissues. Methods in Enzymology. 40, 241-255.
Schultz, E. (1989). Satellite Cell Behaviour During Skeletal Muscle Growth and Regeneration. Medicine and Science in Sports and Exercise. 21 (5), S181-S186.
Sjöstrom, M., Lexell, J., Eriksson, A., Taylor, C.C. (1991). Evidence of Fibre Hyperplasia in Human Skeletal Muscles from Healthy Young Men? European Journal of Applied Physiology and Occupational Physiology. 62, 301-304.
Staron, R.S., & Pette, D. (1987). The Multiplicity of Combinations of Myosin Light Chains and Heavy Chains in Histochemically Typed Single Fibers. Rabbit Soleus Muscle. Biochemical Journal. 243, 687-693.
Staron, R.S., Hagerman, F.C., & Hikida, R.S. (1981). The Effects of Detraining on an Elite Powerlifter. Journal of Neurological Sciences. 51, 247-257.
Staron, R.S., Malicky, E.S., Leonardi, M.J., Falkel, J.E., Hagerman, F.C., & Dudley, G.A. (1989). Muscle Hypertrophy and Fast Fiber Type Conversions in Heavy Resistance-Trained Women. European Journal of Applied Physiology and Occupational Physiology. 60, 71-79.
Tamaki, T., Uchiyama, S., & Nakano, S. (1992). A Weight-lifting Exercise Model for Inducing Hypertrophy in the Hindlimb Muscles of Rats. Medicine and Science in Sports and Exercise. 24 881-886.
Tarnopolsky, M.A., Atkinson, S.A., MacDougall, J.D., Chesley, A., Phillips, S., & Schwarcz, H.P. (1992). Evaluation of Protein Requirements for Trained Strength Athletes. Journal of Applied of Physiology. 73 (5), 1986-1995.
Tarnopolsky, M.A., Atkinson, S.A., MacDougall, J.D., Senor, B.B., Lemon, P.W.R., & Schwarz, H. (1991). Whole Body Protein Leucine Metabolism During and After Resistance Exercise in Fed Humans. Medicine and Science in Sports and Exercise. 23 (3), 326-333.
Tesch, P.A. & Larsson, L. (1982). Muscle Hypertrophy in Bodybuilders. European Journal of Applied Physiology and Occupational Physiology 49, 301-306.
Tesch, P.A., & Karlsson, J. (1985). Muscle Fiber Types and Size in Trained and Untrained Muscles of Elite Athletes. European Journal of Applied Physiology and Occupational Physiology 59, 1716-1720.
Tesch, P.A., Thorsson, A., & Essén-Gustavsson, B. (1989). Enzyme Activities of FT and ST Muscle Fibers in Heavy-Resistance Trained Athletes. Journal of Applied Physiology. 67 (1), 83-87.
Tesch, P.A.. (1988). Skeletal Muscle Adaptations Consequent to long-term heavy resistance exercise. Medicine and Science in Sports and Exercise. 20 (5), S132-S134.
Timson, B.F. (1990). Evaluation of Animal Models for the Study of Exercise-Induced Muscle Enlargement. Journal of Applied Physiology 69, 1935-1945.
Vander, A.J., Sherman, J.H., & Luciano, D.S. (1990). Human Physiology - The Mechanisms of Body Function (5th ed.). New York, NY: McGraw-Hill Publishing Company.
Viidik, A. (1986). Adaptability of Connective Tissue. In B. Saltin (Ed.), Biochemistry of Exercise VI (pp. 545-561). Champaign, Illinois: Human Kinetics Publishers.
Waterlow, J.C., Garlick, P.J., & Milward, D.J. (1978). Protein Turnover in Mammalian Tissue and in the Whole Body. New York, NY: North-Holland.
Weiss, L.W., Cureton, K.J., & Thompson, F.N. (1983). Comparison of Serum Testosterone and Androstenedione Responses to Weight Lifting in Men and Women. European Journal of Applied Physiology and Occupational Physiology. 50, 413-419.
White, T.P., & Esser, K.A. (1989). Satellite Cell and Growth Factor Involvement in Skeletal Muscle Growth. Medicine and Science in Sports and Exercise. 21 (5), S158-S163.
Wong, T.S., & Booth, F.W. (1990). Protein Metabolism in Rat Tibialis Anterior Muscle After Stimulated Chronic Eccentric Exercise. Journal of Applied Physiology. 69, 1718-1724.
Yarasheki, K.E., Campbell, J.A., Smith, K., Rennie, M.J., Holloszy, J.O., & Bier, D.M. (1992). The Effect of Growth Hormone and Resistance Exercise on Muscle Growth in Young Men. American Journal of Physiology. 262 (Endocrinology and Metabolism. 25), E261-E267.
Yarasheki, K.E., Lemon, P.W.R., & Gilloteaux, J. (1990). Effect of Heavy Resistance Exercise Training on Muscle Fiber Composition in Young Rats. Journal of Applied Physiology. 69, 434-437.
For more information please send us mail at email@example.com or call us directly at 613-832-1360.