Thread: How Testosterone permanently effects muscle

Good news for chemical bodybuilders who’d like to change to a steroid-free lifestyle, but are afraid that they’ll lose all the muscle that they’ve so carefully built up. Researchers at the University of Oslo in Norway did tests with mice and discovered that a considerable amount of the effect of testosterone administration on muscle tissue is permanent.

Athletes who’ve managed to – say – do six reps with 120 kg, and then don’t touch a barbell for ten years, will probably lose nearly all the muscle mass they’ve built up. But if they resume training, then they’ll get that lost muscle mass and strength back in no time at all. The phenomenon is called ‘muscle memory’.

In 2010 the Norwegians published an animal study in PNAS in which they described how muscle memory works. [Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15111-6.] We borrowed the figure below from the publication.




If you train muscles the fibres absorb more stem cells. These stem cells then grow into adult muscle cells in the muscles.
The increase in the number of muscle cells in your muscle fibres makes your muscles stronger and bigger. If you stop training, then your muscle cells will become smaller, but the extra cells remain in your muscles.
In 2010 the Norwegians concluded that strength athletes can continue to derive benefit from their muscle strength into old age. Moreover, the researchers suspect that steroids users continue to derive benefit from the courses they’ve taken for years after stopping.
“Anabolic steroids have been shown to increase the number of nuclei”, the researchers write. “Thus, the benefits of using steroids might be permanent and should have consequences for the exclusion time after a doping offense.”
Good news for chemical bodybuilders who’d like to change to a steroid-free lifestyle, but are afraid that they’ll lose all the muscle that they’ve so carefully built up. Researchers at the University of Oslo in Norway did tests with mice and discovered that a considerable amount of the effect of testosterone administration on muscle mass is permanent.
The animal study that will soon be published in the Journal of Physiology shows that the Norwegians were on the right track in 2010. In the new study the researchers implanted pellets containing testosterone propionate [structural formula shown here] in mice [Steroid pellet]. These meant that there was much more testosterone circulating in the animals’ bodies for a period of two weeks than in the bodies of the mice in the control group – the latter had been given an implant that did not contain an active substance [Sham pellet].
As a result of the raised testosterone level, the number of muscle cells in the muscle fibres [Myonuclei] of the mice in the testosterone group increased by 66 percent. Their muscle fibres became 77 percent thicker [CSA].




After fourteen days the researchers stopped administering testosterone propionate. The number of muscle cells in the mice’s muscle fibres remained the same, but the dimensions of the muscle fibres decreased.

After a period of three months the researchers forced the mice to exercise their muscles more than normal for a period of six days [Overload]. The muscles of the mice that had received testosterone grew faster than those of the mice in the other group.
“Our data demonstrate that in least in mice, an episode of testosterone use may recruit a long lasting pool of excess myonuclei, and a persistent increased ability to regain muscle mass by resistance exercise in the absence of further steroid exposure”, the Norwegians write. “Thus, the benefits of even episodic drug abuse might be long lasting if not permanent in athletes. Our data suggests that World Anti-Doping Code calling for only two years of ineligibility after a conviction for steroid use, should be reconsidered.”

The study was partly financed by Anti Doping Norway and the WADA.
A cellular memory mechanism aids overload hypertrophy in muscle long after an episodic exposure to anabolic steroids.

Egner IM, Bruusgaard JC, Eftestøl E, Gundersen K.
Source
University of Oslo, Norway;

Abstract
Previous strength training with or without the use of anabolic steroids facilitates subsequent re-acquisition of muscle mass even after long intervening periods of inactivity. Based on in vivo and ex vivo microscopy we here propose a cellular memory mechanism residing in the muscle cells. Female mice were treated with testosterone propionate for 14 days, inducing a 66% increase in the number of myonuclei and a 77% increase in fibre cross sectional area. Three weeks after removing the drug, fibre size was decreased to the same level as in sham treated animals, but the number of nuclei remained elevated for at least 3 months (>10% of the mouse lifespan). At this time, when the myonuclei-rich muscles were exposed to overload-exercise for 6 days, the fibre cross sectional area increased by 31% while control muscles did not grow significantly. We suggest that the lasting, elevated number of myonuclei constitutes a cellular memory facilitating subsequent muscle overload hypertrophy. Our findings might have consequences for the exclusion time of doping offenders. Since the ability to generate new myonuclei is impaired in the elderly our data also invites speculation that it might be beneficial to perform strength training when young in order to benefit in senescence.

PMID: 24167222 [PubMed - as supplied by publisher]


Testosterone propionate can have permanent effect on muscles, says animal study
Source: A cellular memory mechanism aids overload hypertro... [J Physiol. 2013] - PubMed - NCBI

Sorry links broken here are the photos in order, if PAIN could fix this

Good read.... The theory of muscle memory has been around for as long as I can remember, but is nice to see an up to date study on the subject.

Here is an article from 1996 on Muscle Memory.........

Muscle memory: scientific fact or bodybuilding fantasy?
by Jose Antonio Ph.D
(taken from july 1996 issue of Muscle Media 2000)

The concept of nuclear domain or DNA unit:

Dont' let the science jargon intimidate you. In order to understand how muscle fibers adapt, you'll need to undertand some basic biology. if that bores you then go ahead and turn the page. But if you want to know a little bit more than your average gym rat or meathead then read on.

So what makes skeletal muscle cells or fibers so special? Unlike most cells in the body, skeletal muscle fibers (I'll just refer to them as muscle fibers from now on) are multi-nucleated. That is, within one muscle fiber, you will find hundreds of nuclei. Think of the nucleus (plural nuclei) as the "brain"or "control center" of the fiber. Of course, if you have only one nucleus (e.g., skin tissue) in the cell, then you have only one control center. This control center regulates the amount of genetic material thats available to the cell. How much ribonucleic acid (RNA) and, hence, protien produced is determined by the nucleus.
Research indicates that untrained muscle, slow fibers have a greater myonuclear number than fast fibers even though fast fibers are larger. This is in part related to mitochondrial content. Thus, for a given part of cytoplasmic volume, the nuclei of slow fibers govern a much smaller territory than the nuclei of fast fibers.

So what is the DNA unit? It's defined as "the theoretical volume of cytoplasma associated with a single myonucleus." We know that during postnatal development, nuclei are added to muscle fibers via the proliferation and fusion of satellite cells. Remember, satellite cells are the reserve or stem cells in skeletal muscle involved in repair and growth processes.
Why is this DNA unit so important? Well, some scientists believe that modulating the number of myonuclei may consequently impact the atrophic or hypertrophic response of the muscle.

DNA unit and muscle growth

Recently, scientists examined how myonuclear number and density change in response to muscle hypertrophy. Using a model of compensatory hypertrophy, UCLA scientists removed the gastrocnemius and soleus muscles of cats. This would functionally overload the synergist planaris muscle. This method produced a 152% and 177% increase in slow and fast fibers cross-sectional area, respectively. There was no signifigant difference in the cytoplasmic volume to myonuleus ratio in enlarged slow fibers. This means that as slow fibers hypertrophied, there was a proportional increase in myonuclei. Where did these nuclei come from? The answer is satellite cells.

The picture was different for fast fibers. In this case, there was a signifigant decrease in the cytoplasmic volume to myonulceus ratio. This is due to the fact that myonulcear number increased proportionately more than fiber size. Thus, the DNA unit decreased 25% in fast fibers that were hypertrophied. So now you have a greater absolute number of myonuclei, and these myonuclei govern a much smaller territory. Why is this important?

Scientific speculation

Now you have more nuclei (control centers) governing much smaller local territories. This may represent a possible mechanism for regulating the hypertrophic response. In essence, you have a "better" control over a particular region.

You can use the analogy of how state and local governments work. You can either control how a state parcels out resources via central location, or you can have more local control in that you let city and county governments determine how best to allocate resources. Who would know better how resources in your particular city or county should be distributed? the state (with its control center located far away) or local government (where people have a better idea of what resources are needed)? (Socialists need not answer this.)
I'll assume you answered "local." With an increase in myonuclear density, you now have more "local" control over how a muscle fiber adapts. That is, each region of the muscle knows best how to adapt, depending on the stressors that are imposed on it. This may be important in the hypertrophic response of muscle.

Regional adaption of skeletal muscle:

Weight training, stretch overload, and removal of synergist muscles all result in overall muscle hypertrophy. But we know that not all parts of the muscle adapt equally well. In response to stretch overload, muscle will enlarge more in the proximal and middle regions in comparison to the distal region, while fiber number is greater in the middle region in comparison to either the distal or proximal regions of the muscle belly. Leg extension exercises in humans produce greater hypertrophy in the upper region of the thigh than in the region closest to the knee. Older men who do various biceps exercises have greater hypertrophy near the mid belly of the muscle than in the proximal or distal region. This regionalized response may be related to how each nucleus "senses" how a particular stress is affecting a specific part of the muscle.

Muscle memory at work!:

In one study, a group of women weight trained for 20 weeks, detrained for about 30 weeks, and then retrained for 6 weeks. The 20 weeks of training increased fiber size 16%-47%, while the 30 week detrained period resulted in only a small loss of fiber size (1%-14%). A mere 6 weeks of retraining increased muscle fiber size to levels similar to what were found after the intial 20 weeks of training! Thus, gains made from training seem to be retained for extened periods of detraining, and this, of course, plays a part in the quick return to the highly trained and competetive state of many of the athletes.

What happens to muscle-fiber number?":

There have been no definitive studies in humans (at least at the time this article was published) to determine how fiber number changes in response to detraining; however, our avian friends may have shed some light on the subject. Some of you may remember a previous MM2K article I wrote on muscle fiber hyperplasia [Jan. 96]. In that article, I mentioned the work of several scientists (myself included) who did some work using a stretch model of muscle overload. In essence, one wing has a weight attached to it (about 10% of a birds weight), while the other wing served as the control. In this model of avian weight training (I know I'll get in trouble with other scientists about this, but it's just an analogy, OK?), 30 days of constantly holding a weight resutled in large increases in muscle mass, muscle fiber area, and muscle fiber number! But guess what happened when you removed the weight? Of course, muscle mass goes down. But which decreases the most, muscle fiber area of muscle fiber number? The answer will suprise you.

Thirty days after the removal of the weight, the cross-sectional area or size of the enlarged muscle fibers shrunk back to their original sizes; however, fiber number was higher than the control even 120 days after the removal of the weight! So it seems that, in birds at least, a hypertrophied muscle seems to "want" to keep some of the newly formed formed fibers despite the lack of an overload stimulus. Apparently, losing muscle fiber size is no big deal, but losing newly formed muscle fibers is!

The bottom line:

OK, enough of this science babble. What does this mean to you and your training program? Because each myonulceus governs a small domain, it makes sense that the adaptive response of a muscle fiber is region specific. For example, one study showed that leg extension exercises cause greater growth in the proximal region vs. the distal region. Thus, the myonuclei in the region may have been "stimulated" to increase the synthesis of new muscle protiens. This would suggest that different exercises are needed to stimulate different regions of a muscle in order to produce a maximal increase in muscle volume. That is, there is no single best exercise for producing muscle hypertrophy.

Secondly, the addition of myonuclei to enlarging muscle occurs through the proliferation and fusion of satellite cells to existing muscle fibers. One very important factor in the activation of satellite cells is the exercise-induced damage to muscle fibers. Eccentric contractions seem to do that quite well.

Thirdly, it's not entirely known what happens to myonuclei added to an enlarged muscle fiber when an overload stimulus is removed. Let's say you've lifted hard and heavy for years and, for one reason or another, you take a few months off. You then resume training and find that it takes only a few weeks to recover to your original strength and size. Why? Perhaps when a previously hypertrophied muscle fiber shrinks, it retains a greater proportion of myonuclei (i.e., proportionately greater loss of muscle fiber mass than myonuclei). So now you have a smaller muscle (but still larger than sedentary pencilnecks) but one with proportionately more nuclei. Maybe the muscle fiber is now more sensitized to an internal stimulus (e.g., high tension, injury, exercise) and will respond more quickly by increasing in size. In addition, there may be a neural component to strength that is likely retained when you embark on a retraining program. It's kind of like once you learn to ride a bike, you never forget how.

Why bulking up may be best:

It seems that when you increase the size of a muscle fiber, a period of detraining will shrink it. Nonetheless, it may be more sensitized to regain its original size. Also, when fiber number goes up, your muscle apparently prefers keeping these new fibers in spite of the loss of total muscle fiber mass. Thus, it may be best for bodybuilders to gain as much weight as possible ("by any means necessary") and put as on as much muscle as possible. The drawback is, of course, added fat.

However, the use of anrogens or anabolic steriods may preclude this. One the other hand, if you are natural, eating well, doing no aerobic exercise, and lifting heavy weights (i.e., low volume, high intensity), you'll accrue signifigant muscle mass. The next step after this bulking-up period is the attempt to lose the added fat while sparing muscle. Then you embark on a lowerfat, lower caloric diet; do a little bit of aerobic exercise, and do higher volume, lower intensity weight training. You'll lose fat and perhaps a little bit of muscle. But remember, if your muscle had memory, it will want to keep any newly formed fibers and retain added myonuclei. Then when you resume the low-volume, high-intensity phase of your weight training program, you will regain that lost muscle mass much quicker than if you had never bulked up to begin with. I personally believe it's easier to lose fat than it is to gain muscle (some women would probably disagree). So put on muscle now, and lose fat later.

This may explain why heavy androgen users can maintain a high degree of muscularity after a long period of detraining. They've previously put on so much muscle mass, they're just sensitized to regain lost muscle mass once an intense training regimen comences.

Of course, in bulking up, you may run into a problem. Let's not hope that fat cells have memory.