January 24, 2000 (Volume
3, Number 2)
Research Update
by Bryan Haycock MSc., CSCS
bryan@thinkmuscle.com
Please send us your feedback on
this article.
As we approach the new millennium we find the science of building
muscle progressing faster than ever before. Long gone are the days of
simple trial and error when it comes to building muscle. The modern
bodybuilder demands more than just "hear say" if they are to adopt a new
training routine or nutritional supplement. This column was created to
keep today’s bodybuilder on the cutting edge of scientific research that
might benefit them in their quest for body perfection.
Are steroids your key to preventing Andropause?
Title:
Long-term suppression of leydig cell steroidogenesis
prevents leydig cell aging.
Researchers:
Chen H, Zirkin BR
Division of Reproductive Biology, Department of Biochemistry and
Molecular Biology, Johns Hopkins University, School of Hygiene and Public
Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Source:
Proc Natl Acad Sci U S A 1999 Dec 21;96(26):14877-81
Summary:
Based on the observations that reactive oxygen is capable of damaging
components of the steroidogenic pathway and that reactive oxygen is
produced during steroidogenesis itself, we hypothesized that long-term
suppression of steroidogenesis might inhibit or prevent age-related
deficits in Leydig cell testosterone production. To test this, we
administered contraceptive doses of testosterone to groups of young (3
months old) and middle-aged (13 months old) Brown Norway rats via Silastic
implants to suppress endogenous Leydig cell testosterone production. After
8 months, the implants were removed, which rapidly (days) restores the
ability of the previously suppressed Leydig cells to produce testosterone.
Two months after removing the implants, when the rats of the two groups
were 13 and 23 months of age, respectively, the Leydig cells in both cases
were found to produce testosterone at the high levels of young Leydig
cells, whereas significantly lower levels were produced by the
23-month-old controls. Thus, by placing the Leydig cells in a
state of steroidogenic "hibernation," the reductions in Leydig cell
testosterone production that invariably accompany aging did not occur.
If hormonal contraception in the human functions the same way, the adverse
consequences of reduced testosterone in later life (osteoporosis, reduced
muscle mass, reduced libido, mood swings, etc.) might be delayed or
prevented.
Discussion:
OK, I will admit that I am biased about the use of androgens. Frankly,
I think politicians and the popular press have unjustly vilified them.
This being the case I tend to take notice to studies involving androgens.
This particular study was a real surprise.
Male aging is accompanied by reduced testosterone production by the
Leydig cells, the testosterone-producing cells of the testis. The
mechanism by which this occurs is unknown. In the above study they
suppressed testosterone production with androgen implants in male rats for
eight months. The researchers called this behavior of the testes as
"steroidogenic hibernation".
This is the same phenomenon that all male bodybuilders experience when
using testosterone of other androgens. After removing the hormone implants
they measured the ability of the leydig cells to produce testosterone by
bathing them in luteinizing hormone (LH). They measured testosterone
production as well as steroidogenic enzyme activities. As you can see from
the graph above, the leydig cells of old rats that had their testosterone
production temporarily shut down, retained their ability to produce
testosterone equal to young rats. The activities of each enzyme tested
were significantly lower in Leydig cells from the 23-month-old control
rats compared with the 13-month-old control rats. All the steroidogenic
enzyme activities were reduced in Leydig cells isolated from 11- and
21-month-old rats tight after exogenous testosterone treatment for 8
months. Two months after the implants were removed, when the rats were 13
and 23 months of age, respectively, the activities of each of the
suppressed enzymes were at the high levels of 13-month-old control rats,
in each case significantly higher than those of the 23-month-old controls.
The researchers hypothesize that this phenomenon is the result of
decreased oxidative damage to leydig cells. In the course of normal cell
function, reactive oxygen species are produced and can cause damage to
DNA, proteins (e.g. enzymes), and cell membranes including mitochondrial
membranes. This could contribute to age related loss of testosterone
production. It is known that reactive oxygen species can damage the
steroidogenic pathway in vitro (Quinn, 1985).
The authors of this study considered the dose of testosterone needed to
accomplish this as a "contraceptive" dose. In men this is about 100 mg
testosterone enanthate per week. They will usually throw in some
progesterone too. This is far below what you would need to be a
competitive bodybuilder. It could be that in doses used by larger
bodybuilders is too much and may actually cause permanent losses in
testosterone production. On the other hand, these doses might be equally
effective or even more so than contraceptive doses. Time will tell. In any
case, a preservation of testosterone production in later life means
decreased risk of osteoporosis, sarcopenia, loss of strength, mood swings,
etc. Appropriate studies carried out on humans is clearly needed.
Quinn PG, Payne AH. Steroid product-induced, oxygen-mediated damage of
microsomal cytochrome P-450 enzymes in Leydig cell cultures. Relationship
to desensitization. J Biol Chem 1985 Feb 25;260(4):2092-9
Taking a closer look at the muscles of steroid using athletes... A
really close look.
Title:
Effects of anabolic steroids on the muscle cells of
strength-trained athletes.
Researchers:
Kadi F, Eriksson A, Holmner S,
Thornell LE Department of Integrative Medical Biology, Umea University,
Sweden.
Source:
Med Sci Sports Exerc 1999
Nov;31(11):1528-34
Summary:
Athletes who use anabolic steroids get larger and stronger
muscles. How this is reflected at the level of the muscle fibers has not
yet been established and was the topic of this investigation. METHODS:
Muscle biopsies were obtained from the trapezius muscles of high-level
power lifters who have reported the use of anabolic steroids in high doses
for several years and from high-level power lifters who have never used
these drugs. Enzyme-immunohistochemical investigation was performed to
assess muscle fiber types, fiber area, myonuclear number, frequency of
satellite cells, and fibers expressing developmental protein isoforms.
RESULTS: The overall muscle fiber composition was the same in both
groups. The mean area for each fiber type in the reported steroid users
was larger than that in the nonsteroid users (P < 0.05). The number of
myonuclei and the proportion of central nuclei were also significantly
higher in the reported steroid users (P < 0.05). Likewise, the frequency
of fibers expressing developmental protein isoforms was significantly
higher in the reported steroid users group (P < 0.05).
CONCLUSION: Intake of anabolic steroids and
strength-training induce an increase in muscle size by both hypertrophy
and the formation of new muscle fibers. We propose that activation of
satellite cells is a key process and is enhanced by the steroid use.
The incorporation of the satellite cells into preexisting fibers
to maintain a constant nuclear to cytoplasmic ratio seems to be a
fundamental mechanism for muscle fiber growth. Although all the subjects
in this study have the same level of performance, the possibility of
genetic differences between the two groups cannot be completely excluded.
Discussion:
This study was trying to answer one basic question, "How do anabolic
steroids produce muscle growth?" If you were to ask the average
bodybuilding enthusiast I think you would hear, "they increase protein
synthesis." This is not untrue, its just that it is only part of the
answer. In fact, the answer must include virtually every mechanism
involved in skeletal muscle hypertrophy. These include:
- Enhanced growth factor activity (e.g. GH, IGF-1, etc.)
- Enhanced activation of myogenic stem cells (i.e. satellite cells)
- Enhanced myonuclear number (to maintain nuclear to cytoplasmic
ratio)
- Enhanced protein synthesis
- New myofiber formation
You can read more about these mechanisms
elsewhere in Mesomorphosis . Now, where do androgens fit in to this?
Starting with growth factor activity, we know that testosterone increases
GH and IGF-1 levels. In a recent study by Fryburg (Fryburg, 1997) the
effects of testosterone and stanozolol were compared for their effects on
stimulating GH release. Testosterone enanthate (only 3 mg per kg per week)
increased GH levels by 22% and IGF-1 levels by 21% whereas oral stanozolol
(0.1mg per kg per day) had no effect whatsoever on GH or IGF-1 levels.
This study was only 2-3 weeks long, and although stanozolol did not effect
GH or IGF-1 levels, it had a similar effect on urinary nitrogen levels.
What does this difference between testosterone and stanozolol mean? In my
opinion it means that stanozolol can increase protein synthesis by binding
to AR receptors in existing myonuclei, however, because it does not
increase growth factor levels it is ineffective at activating satellite
cells and therefor may not increase satellite cell activity and thus
myonuclear number.
Enhanced activation of satellite cells requires IGF-1. Those
androgens that aromatize are effective at not only increasing IGF-1
levels but also the sensitivity of satellite cells to growth factors (Thompson, 1989). This action has no direct effect on
protein synthesis. It leads to a greater capacity for
protein synthesis by increasing fusion of satellite cells to existing
fibers. This increases the number of myonuclei and therefore the
capacity of the cell to produce proteins.
So it is not only that testosterone increases protein
synthesis by activating genetic expression, it also increases the
capacity of the muscle to grow in the future by leading to the
accumulation of myonuclei which are required for protein synthesis. There
is good reason to believe that testosterone in high enough doses may even
encourage new fiber formation. To quote the authors of this study:
"Intake of anabolic steroids and strength-training induce an increase
in muscle size by both hypertrophy and the formation of new muscle
fibers. We propose that activation of satellite cells is a key process
and is enhanced by the steroid use."
Just a note for those of you who will use androgens but
refuse to use supplements. There is good evidence that creatine
specifically stimulates the formation of myofibrillar protein in newly
developing fibers (Ingwall, 1972; 1974; 1975; 1976). The effect is
concentration dependent, maxing out at about 250 µM. Normal plasma
concentrations are about 100 µM. In my opinion, creatine supplementation
is certainly called for in athletes using heavy androgens.
A separate argument related to this study
I would like to quickly address a separate issue related to steroid
use. Although I believe Bill Roberts has competently addressed
this issue previously in
earlier issues of Mesomorphosis, I would like to make my own contribution
here. It has been thought, and is still commonly believed, that using
steroids decreases the number of "steroid" receptors. This argument is
used to explain the fact that growth eventually stops while using a given
amount of steroid. Once you understand all of the effects of
testosterone on growth factor levels and muscle cells you come to realize
that the opposite is in fact the case. Simply stated, supraphysiological
levels of testosterone gives rise to increased numbers of myonuclei and
thereby an increase in the number of total androgen receptors per muscle
fiber. Therefor, the larger you get from using steroids, the more
receptive your muscle become to the presence of testosterone. Keep in mind
that I am referring to testosterone and testosterone esters. Not the
neutered designer androgens that people take to avoid side effects
(Fryburg, 1997). This is not an argument to rapidly increase the dosages
you use. It takes time for these changes to occur and the benefits of
higher testosterone levels will not be immediately realized.
Fryburg DA., Weltman A., Jahn LA., et al: Short-term modulation of the
androgen milieu alters pulsatile, but not exercise- or growth hormone
releasing hormone-stimulated GH secretion in healthy men: Impact of
gonadal steroid and GH secretory changes on metabolic outcomes. J Clin
Endocrinol. Metab. 82(11):3710-37-19, 1997
Thompson SH., Boxhorn LK., Kong W., and Allen RE. Trenbolone alters the
responsiveness of skeletal muscle satellite cells to fibroblast growth
factor and insulin-like growth factor-I. Endocrinology.
124:2110-2117, 1989.
Ingwall JS, Morales MF, Stockdale FE, Wildenthal K.
Creatine: a possible stimulus skeletal cardiac muscle hypertrophy.
Recent Adv Stud Cardiac Struct Metab 1975;8:467-81
Ingwall JS, Morales MF, Stockdale FE. Creatine and the
control of myosin synthesis in differentiating skeletal muscle. Proc
Natl Acad Sci U S A 1972 Aug;69(8):2250-3
Ingwall JS, Weiner CD, Morales MF, Davis E, Stockdale
FE. Specificity of creatine in the control of muscle protein synthesis.
J Cell Biol 1974 Jul;62(1):145-51
Ingwall JS, Wildenthal K. Role of creatine in the
regulation of cardiac protein synthesis. J Cell Biol 1976
Jan;68(1):159-63
Even pathetic training routines can cause hyperplasia in
untrained women.
Title: Training affects
myosin heavy chain phenotype in the trapezius muscle of women.
Researchers:
Kadi F, Thornell LE. Department of
Anatomy, Umea University, Sweden.
Source:
Histochem Cell Biol 1999 Jul;112(1):73-8
Summary:
The aim of this investigation was to determine whether 10 weeks of
three different types of training could alter the myosin heavy chain
(MyHC) composition of the trapezius muscle. Twenty-one women were randomly
assigned to three training groups that performed strength (n=9), endurance
(n=7) or coordination training (n=5). Pre and post biopsies were taken
from the upper part of the descending trapezius muscle and were analyzed
for MyHC isoform content using 5% gel electrophoresis. In addition, we
have studied the expression of embryonic and neonatal MyHCs using
double-immunofluorescence staining. In the strength-trained group, there
was a significant increase in the amount of MyHC IIA and a significant
decrease in the amount of MyHC IIB and MyHC I. In the endurance group,
there was a significant decrease in the amount of MyHC IIB. MyHC
composition in the coordination group was not altered. Following the
training period, myotubes and individual small-sized muscle fibers were
observed in the strength and endurance trained groups. These structures
were stained with the markers for early myogenesis (MyHC embryonic and
neonatal). These data suggest that specific shifts in MyHC isoforms occur
in the trapezius muscle following strength and endurance training.
The presence of small-sized muscle fibers expressing the
developmental isoforms of MyHC suggests that strength and endurance
training induced the formation of new muscle fibers.
Discussion:
The title of this study doesn’t immediately grab your attention,
however, after reading the results we are witness to a paradigm shift in
thought. Let me clarify by stating that this paradigm shift is occurring
in the ivory towers of academia, not in the more progressive thinking
minds in bodybuilding. This shift is occurring to accommodate the fact
that human adult muscle tissue does experience hyperplasia.
This is not the first study to shown the formation of new muscle fibers
as a result of training. Even this same group has shown hyperplasia to
occur in power lifters (Kadi, 1999). However, this is the only one I have
came across involving previously untrained women.
In this study, groups of women participated in rather mild exercise
programs. One group lifted weights (3X10-12 reps), another group used an
upper body cycle ergometer (4X3 minutes) combined with very easy arm
exercises with elastic bands (30 reps). The final group performed
yoga-like exercises emphasizing balance and serenity with insignificant (I
assume without weights of any kind) resistance during movements. Following
the training period, newly formed myotubes and individual small-sized
muscle fibers expressing embryonic and neonatal proteins were observed in
both the strength and endurance trained groups. The amount of these small
fibers producing neonatal and embryonic proteins was small (~3%)
nevertheless, they were clearly a result of the exercise. Previous
investigations of power lifters found the same relative proportion of
newly forming fibers as a result of training (Kadi, 1999).
The power lifters in a subsequent study by Kadi were highly competitive
and participated in Swedish national and international competitions. This
is in stark contrast to the study above. The athletes in this later study
participated regularly in international competitions (World
Champion-ships, European Championships and Swedish Championships in power
events). The athletes trained regularly for 2–3 hours, 4–6 times a week.
The sessions consisted of 4–7 sets of exercises that were repeated 3–12
times per session. These athletes claimed to have never used anabolic
steroids. They were selected from the same club where they signed a
contract that committed them never to use any drug. Four of them
participated voluntarily as controls for another project aiming to find
more effective methods to detect drugs. As in this study, they found an
average of ~3% small fibers producing neonatal and embryonic proteins.
As I have predicted in the past, future bodybuilding training routines
will focus on producing damage instead of strength or fatigue. Of course
the later two are inevitable consequences of training, nevertheless,
efficiency will depend on narrowing our focus on the true stimulus of
muscle growth, namely fiber microtrauma and subsequent activation of
satellite cells. I currently have many of my clients using just such a
routine training every body part three times per week, focusing on load
(more weight, more stretch, more eccentrics, more frequency, more
soreness.) instead of high volume, waiting for complete recovery,
"strength endurance" training (my description of how most natural
bodybuilders train). Soft tissue massage is also an integral yet difficult
to obtain factor which enhances activation of satellite cells. Early
results are promising. All (both men and women) who are using my system
are sore almost continuously despite minimal training volume and are
making new personal records in both size and strength.
Kadi F · Anders Eriksson · Staffan Holmner Gillian S.
Butler-Browne · Lars-Eric ThornellCellular adaptation of the trapezius
muscle in strength-trained athletes. Histochem Cell Biol (1999)
111:189–195
Please send us your feedback on
this article.
by Bryan Haycock MSc., CSCS
bryan@thinkmuscle.com
