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by Dharkam
Disclaimer: Discussion of pharmaceutical agents below is presented for
information only. Nothing here is meant to take the place of advice
from a licensed health care practitioner. Consult a physician before
taking any medication.
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.
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.
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.
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.
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 building tools.
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.
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