Muscular Adaptations to Resistance Training With Special Emphasis on Muscle Fiber and Whole Muscle Hypertrophy

INTRODUCTION

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

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).

Protein Synthesis

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.

Hypertrophy

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.

Hyperplasia

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.

SUMMARY

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.

References

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.

Posted in Research.