In the January 1999 issue of the American Journal of Physiology, a new study performed on astronauts during spaceflight demonstrates the key role played by prostaglandins in maintaining the strength of muscles. A major problem during spaceflight is the rapid loss of lean muscle mass in both animals and humans. This prevents the space agencies from sending men into space for extended periods without threatening their health. It is, of course, the lack of resistance and weight due to the weightlessness that is the cause of muscle atrophy. The million dollar question is: how does this lack of resistance alter the intracellular environment so that muscle wasting is free to take place?
Why are these experiments relevant to bodybuilders? Simply because the pathways triggering the muscle wasting in space flight are the same that make our muscle grow when we train. They just work in opposite directions in each case.
Hormone fluctuations during spaceflight
Hormones are obvious candidates as possible mediators of this wasting process. The favored hypothesis is that spaceflight induces some major alterations in our hormone levels. Two main pathways could be involved. First, the levels of catabolic hormones could rise and so be the cause of this wasting. Second, the level of the anabolic hormones could drop so that the constant basal renewal of muscle protein could not take place at a sufficient rate, resulting in a net negative balance.
Cortisol
The study by Dr. Peter Stein [1] of the University of Medicine and Dentistry of New Jersey consisted of measuring the key hormones in astronauts during a space shuttle mission. Cortisol, a known wasting hormone, was one of the favorite candidates. Unfortunately, a consistent pattern of fluctuations in cortisol level was not apparent. Cortisol increased in some but not all subjects. As all of them experienced significant muscle loss, cortisol excess does not explain the consistent wasting. Another paradox is that, once back on the ground, the astronauts regained lean body mass while cortisol level was at its peak.
This means that you can waste away while having a normal cortisol level, and you can put on lean mass despite a high cortisol level. It should be a major eye-opener for bodybuilders.
Catecholamines
Next on the list of candidates were the catecholamines (epinephrine and norepinephrine). Depending on whom you listen to, catecholamines are either anti-catabolic or catabolic. Whatever their effect, every scientist would agree that it is at best mild. The expected drops and rebounds of catecholamines were detected during the flight and the post flight periods, respectively. To explain the lean mass fluctuations, it would mean that catecholamines are very potent anabolic or anti-catabolic substances — information that no research has ever demonstrated even at high doses in humans. So they are not the mediator the scientists were looking for.
Anabolic Hormones and Growth Factors
The next substances to be measured were the anabolic hormones and growth factors such as GH, IGF-1 or insulin. Stein did not find any significant alteration of their levels taking place during the phase of wasting or regrowth. He did notice that T3 (an active thyroid hormone) level dropped during the flight, to rebound after landing. T3 fluctuations concur with the mass loss and regain, so Stein suggests that T3 could be one of the mediators of the lean mass fluctuation. As T3 drops during the flight, so would the rate of muscle protein synthesis. After landing, the increased T3 would boost anabolism and therefore muscle growth.
I disagree with Stein on this point. I consider the space-induced drop in T3 as a protective mechanism against excessive muscle wasting rather than a mediator of the growth inhibition. T3 is both an anabolic and catabolic hormone. A minimal amount of T3 is required for muscle to grow at an optimal rate, but as the T3 level increases, its catabolic actions start to predominate and overwhelm its anabolic properties.
This is why you’ll never meet a bodybuilder claiming to have gained muscles by taking only T3. In fact, bodybuilders using T3 start to lose both lean and adipose mass. Studies performed in bed-rested people which attempt to duplicate weightlessness showed that in this situation, exogenous T3 promoted protein degradation and not anabolism. Therefore, T3 is unlikely to be the mass modulator we are looking for.
Prostaglandins
Stein’s genuine breakthrough came from the fact that he measured the levels of prostaglandins in both the blood and urine and compared them with the degree of muscle wasting.
Both measures were used for better accuracy as the levels of prostaglandins are very hard to evaluate, prostaglandins being mainly a local and not systemic growth modulator. Skeletal muscles and bones are both net producers of prostaglandins with muscles being the major site of manufacture. Those locally produced prostaglandins will eventually pass into the blood before being quickly destroyed. So the blood level of prostaglandins roughly reflects the rate of production of prostaglandins inside the muscles. With urine prostaglandins, results tend to be harder to interpret as prostaglandins produced in the kidney tend to bias the figures. Nevertheless, Dr. Stein found out that both measures agreed anyway.
To the surprise of the scientific community (but not to bodybuilders), the levels of the prostaglandins measured dropped during the flight — especially the PGE2.
After landing, there was a significant rebound of the prostaglandin levels, especially of the PGF2. Those fluctuations closely reflected the observed changes in lean muscle mass.
The major cause of this drop is the lack of resistance placed on both the muscles and bones. As we flex our muscles, a local formation and release of prostaglandins is taking place. The harder we flex, the more the local level of prostaglandins is elevated. Weightlessness prevents the astronauts from flexing their muscles against a resistance. Therefore, a significant drop in muscle prostaglandins can be expected. As less prostaglandins are produced in our muscles, the drop will quickly be reflected by the blood measurements.
This may explain the well known development of insulin resistance occuring during space flight as prostaglandins mediate many of the actions of insulin on muscles. This resistance also contributes to the muscle protein loss and again we find prostaglandins as key mediators of this phenomenon.
Stein’s interpretations of these new findings are somewhat less convincing. Scientists are expected to accurately measure the results they obtained during an experiment, but also they are also expected to interpret their results. Sometimes, their discussion is well researched and documented which provides a worthwhile reading. Unfortunately, many times it is not so well researched and the discussion is a big step backward. This is the case in the above mentioned study. The basic ideas are bright and the results original but the comments made by the team of scientists is at the very least poor. Paradoxally, they reached a good conclusion with a biased reasoning.
The discussion part of this study is based on a very selective reading of the scientific literature while the bottom line conclusion is very good. It concludes that “the inflight data support a major role for decreased prostaglandin production in the protein loss by muscles.” This is very refreshing as the average scientist considers prostaglandins as mediators of wasting and certainly not of muscle growth. Stein’s conclusion fits very well with his findings. The fall in muscle prostaglandins induced by the lack of resistance during the spaceflight results in a sharp fall in protein synthesis.
For a quick recap:
- Our muscles are subjected to a constant protein turnover. This means that the old proteins composing the contractile tissue of each cell are constantly destroyed (catabolism) and replaced by new proteins (anabolism).
- If you are a sedentary person between 20 to 40 year old, this constant basal turnover is neutral. The rate of catabolism is roughly equal to the rate of anabolism.
- Young growing adolescents acquire their muscle mass as anabolic rate exceeds catabolism.
- Elderly people slowly waste away as anabolism is slower than degradation.
- During spaceflight, anabolism is reduced, causing the rebuilding mechanisms to be overwhelmed by the catabolic pathways. A loss of lean mass ensues.
The big issue is to understand which hormones or factors are involved in the drop of anabolism.
Stein based his reasoning on the common belief concerning prostaglandins, i.e., that PGF2 is anabolic and PGE2 is catabolic. From there, he tries to explain how PGE2, a catabolic factor according to him, could make our muscle grow. Good luck! Also, if PGE2 is a key mediator of muscle wasting as many believe, how to explain its drop while catabolism is intense? This belief concerning the so-called wasting effect of PGE2 is due to some old, badly conducted, and flawed studies which other laboratories have been unable to reproduce. Other newer and more comprehensive studies have shown that PGE2 has an overall positive influence on the protein turnover [2]. In other words, PGE2 is an anabolic mediator rather than a catabolic one.
This fits better into the NASA findings. During the flight, muscle prostaglandins fall, which depresses anabolism. After the flight, muscle prostaglandin production bounces back as astronaut muscles are once against submitted to the resistance of gravity. The extra prostaglandins strongly stimulate anabolism which explains the fast muscle rebuilding.
Let’s speculate a little!
With this major role of prostaglandins in mind, let’s try to go a bit further. Scientists specializing in Aeronautics have spent years trying to combat space-induced wasting. In fact, the main research on bodybuilding hormones has mostly been conducted by those scientists. They have tried to administer hormones such as GH or IGF-1 during spaceflights in order to combat the muscle loss. They have had little success — hardly surprising in light of recent findings. As the levels of these peptide hormones hardly fluctuate, administering some more does not appear to be the optimal solution. Usage of anabolic steroids during weightlessness has achieved some but not exceptional results. The next step is now to administer prostaglandins during a flight and see what will happen.
The lack of effects of the tested anabolic hormones on muscles suggests that their receptors failed to function normally. In other words, the lack of muscle contractions rapidly produce a receptor insensitivity. What if it was the level of muscle prostaglandins that was one of the major controllers of the sensitivity of the main anabolic hormones? I’ve mentioned that the potency of steroids was enhanced by exogenous PGF2. By the same token, PGF2 sensitivity is enhanced by androgens.
So:
- Prostaglandins control androgen and IGF-1 receptor activities.
- Androgens control prostaglandin receptor expression.
- IGF-1 and anabolics are major controllers of the level of muscle prostaglandins.
This looks like a righteous anabolic cycle. Therefore, the major issue for the scientists of the third millennium is to figure out how, at which part of the cycle and where to enter this anabolic cycle for maximal effectiveness of our muscle
References:
- Stein TP. 1999 Jan. Endocrine relationships during human spaceflight. Am J Physiol. 276:E155-62.
- Fagan JM, Goldberg AL. 1986 Apr. Inhibitors of protein and RNA synthesis cause a rapid block in prostaglandin production at the prostaglandin synthase step. Proc Natl Acad Sci U S A. 83(8):2771-5.
About the author
The true identity of the infamous Michalovich Dharkam Greutstein cannot be revealed. The obscurity relating to "Dharkam", is due to certain European laws governing writing about drugs and medicines. Freedom of speech is by no means universal. When a scientist sees an interesting topic relating to his area of expertise, but cannot publish on it due to this sort of repression, sometimes he publishes under a pseudonym. In fact, publishing tracts under a pseudonym is a centuries-old tradition in Europe, and was prevalent in the U.S. until the Revolution secured this freedom for U.S. citizens.
"Dharkam. That’s not his real name, but he’s a really smart guy. He’s one of the two or three people that I really trust. Now, he is probably the only one, outside of myself, that gets really creative with the research. It seems that everybody else is timid with the research, and you have to have a little bit of recklessness to be able to push the state-of-the-art of bodybuilding forward... "
"If Dharkam says it works, it probably does work. I know there is no research on it, but he’s probably right. I have known this man for at least three or four years. He’s always been thought provoking, and many times, when people disrespect him and say he’s full of shit, he always pulls a reference to validate whatever he said. " -- Dan Duchaine, January 2000
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