- Jun 25, 2006
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Prostaglandins and Protein Synthesis
When most of us think of the hormones in the body that are responsible for building muscle, usually testosterone, growth hormone (via IGF-1) and insulin come to mind. These are the “big three,” so to speak. By no coincidence, these are the same three hormones we find bodybuilders manipulating levels of or supplementing in various synthetic drug forms to aid in the pursuit of “hugeness.” But, when it comes to understanding the underlying mechanisms involved in muscle growth, there is more to it than just these three hormones. In fact, there is another class of hormonal compounds involved in the regulation of skeletal muscle protein that are necessary for the accumulation of new mass. These hormones are called prostaglandins and they are too often overlooked when it comes to discussions about what is controlling muscle growth in our bodies. As you will see, they are among the most vital components in the stimulation of protein synthesis and the support of skeletal muscle growth, and you couldn’t gain a single ounce of new muscle without them.Prostaglandins are derivatives of fatty acids produced in various tissues in the body including liver, adipose, and smooth and skeletal muscle. They are called prostaglandins, incidentally, because the first hormone labeled as such was isolated in semen back in the 1930s and was thought at the time to be originating from the prostate itself. Some time later, scientists realized how widely distributed hormones of this type are, and they’ve come to identify different prostaglandin compounds, about 20 in all, in almost every tissue of the body. As a group they have varying physiologic actions, such as modulating immune system function, inflammation, temperature, blood platelet aggregation, smooth muscle contraction and protein turnover in skeletal muscle tissue. The latter role is of primary interest to us, of course, and upon close inspection we see clearly that these hormones are much more than just simple peripheral supporters of protein synthesis. They are, in fact, right there at the very core of muscle growth.
Stretch Stimulus
Prostaglandins begin to exert their strong effects on muscle growth immediately following physical exertion. More specifically, it is the stretch stimulus provided by muscle contractions that first triggers the local release of prostaglandins. These, in turn, play a pivotal role in what will be going on in your muscle cells during the following 48 hours or so of recovery. A study published in 1990 in the American Journal of Physiology looked perhaps most closely at the relationship between prostaglandins, protein turnover and physical exercise.[1] In this investigation, various skeletal muscle cell preparations were incubated under stretch stimulus to replicate the damage induced by exercise. Protein turnover, as measured by the incorporation of the labeled amino acid phenylalanine, was quantified.During the first five hours of stimulation, PGE2 and PGF2alpha prostaglandin levels increased 101 and 41percent, respectively. PGE2, shown in other studies to play a role in increasing protein breakdown,[2] returned to normal levels within 24 hours of mechanical stimulation. PGF2, on the other hand, remained elevated for 48 hours and correlated with a 52-98 percent long-term increase in protein synthesis. The study suggests we are seeing the regulation of protein turnover in two different directions by prostaglandins. PGE2 is tied to the damage initially induced by resistance exercise, and PGF2alpha, the subsequent long-term increase in protein synthesis that rebuilds and strengthens muscle tissue.
Prostaglandin Inhibition
It is perhaps easiest to see just how vital prostaglandins are to muscle growth by looking at what happens when we inhibit their production. This was detailed extremely well in a study conducted in 2001 at the University of Arkansas.[3] In this investigation, a group of 24 recreationally active young male subjects were given maximum OTC doses of ibuprofen (1,200mg/day) or acetaminophen (4,000mg/day), or placebo, and subjected to resistance training. These two popular over-the-counter pain relief medications are known to exert their analgesic effects in the body by inhibiting the cyclooxygenase enzyme, which is responsible for prostaglandin production.[4] [5] Amino acid turnover was measured for 24 hours following the bout of exercise, which allowed the investigators to determine what effect, if any, these drugs would have on protein breakdown and synthesis. The results were startling, and would cause any bodybuilder to think twice before popping one of these OTC pain medications again. Both ibuprofen and acetaminophen effectively blunted the normal post-exercise rise in protein synthesis, which was increased 76 percent above baseline in the group taking only the placebo. This study showed us clearly, and for the first time, that the OTC drugs many of us routinely use to combat muscle soreness actually interfere with the basic process of muscle growth. It is almost as if the workout never even happened in the first place!After the stunning results of the first study, a follow-up investigation was conducted to look more closely at the underlying mechanisms in which ibuprofen and acetaminophen were interfering with post-exercise protein synthesis.[6] Every effort was used to replicate the conditions of the first study, including the use of the same exact group of male subjects (24 in total). The same drug and exercise protocols were followed as well, which entailed maximum daily OTC doses of ibuprofen or acetaminophen and 10-14 sets of Cybex machine knee extensions to failure. This time, however, they did not look at changes in protein turnover, probably because they were already established on these men under the same conditions. Instead, they looked at what effect these drugs would have on the levels of those prostaglandins normally thought to play a role in protein turnover. The results probably could have been expected given what we learned from the earlier stretch stimulus study. Both OTC analgesics strongly blunted the normal post-exercise rise in— you guessed it— PGF2alpha. Acetaminophen additionally suppressed levels of PGE2, while Ibuprofen and placebo both did not interfere with PGE2 release. As was the case with the 1990 study, the end results pointed to PGF2alpha as being the prostaglandin most closely tied to the stimulation of post-exercise protein synthesis.
In Closing
The buildup and breakdown of skeletal muscle mass in the human body is controlled by the complex interaction of a myriad of different components too numerous to cover in a single article, and all too vital to the process as a whole to ignore. When it comes to the level of hormonal regulation specifically, however, we still see that there is not one, but several, hormones integral to what is going on. Given the recent attention to the role prostaglandins play in this process, we can say for certain that no discussion about the underlying hormonal controls of muscle growth could be complete without their mention. It’s also worth noting that a synthetic drug form of PGF2alpha, sold in the U.S. as Lutalyse (diniprost), has recently started eking its way into the gym bags and medicine cabinets of bodybuilders across the country. Although a discussion of its implementation, benefits and potential side effects goes well beyond the scope of this article, it can be said that many people have been reporting extremely positive results with this drug. We can likewise expect its use will be well explored as we go further into the twenty-first century. In the end, we see that prostaglandins, or perhaps more specifically PGF2alpha, indeed do deserve a place right next to the “big three” muscle-builders, testosterone, GH and insulin, as without all four of these hormones doing their part, there simply is no muscle growth.
References
[1] Stretch-induced prostaglandins and protein turnover in cultured skeletal muscle. Vandenburgh et al. Am J Physiol v.259 pg.C232-40
[2] Rodemann, Goldberg et al. J Biological Chem 257(4) 1632-38 1982
[3] Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Trappe, White et al. Am J Physiol Endocrinol Metab. 2002 Mar;282(3):E551-6.
[4] Mechanism of acetaminophen inhibition of cyclooxygenase isoforms. Ouellet M, Percival MD. Arch Biochem Biophys 2001 Mar 15;387(2):273-80
[5] Inhibition of cyclooxygenase-1 and -2 by R(-)- and S(+)-ibuprofen. Boneberg EM, Zou MH, Ullrich V. J Clin Pharmacol 1996 Dec;36(12 Suppl):16S-19S
[6] Skeletal muscle PGF(2)(alpha) and PGE(2) in response to eccentric resistance exercise: influence of ibuprofen acetaminophen. Trappe, White et al. J Clin Endocrinol Metab. 2001 Oct;86(10):5067-70.
Black Market Update
The world supply of Oxymetholone took another big hit recently. Hemogenin, which was at one time one of the most popular forms of oxymetholone (Anadrol®) to be imported into the U.S., is no longer being manufactured. This preparation was made by the Brazilian company Sarsa, which licensed the rights to it from Syntex, the world’s first and leading producer of the drug. It was sold in blisters of 10 tablets in both the U.S. and Brazilian markets for a very reasonable price. Apparently, a lot of public attention has been given to anabolic steroids in this country in recent years, and the government felt there was no longer any legitimate medical need to keep the drug around. At one time oxymetholone was readily used for certain anemic conditions, where it was quite successful at increasing red blood cell production due to the action steroids have on erythropoiesis (the process of red blood cell production). The advent of synthetically manufactured erythropoietin (a hormone much more directly tied to blood cell production) made oxymetholone obsolete, however. So the drug remains now in only a few corners of the world where it is either used for HIV+ muscle wasting, or continues to be sold solely because of its popularity with athletes. Pictured here also is an underground generic Anadrol (labeled simply oxymetholone 50) from the firm Alpha Tech. The tablets themselves are light blue in color, and contain an imprinted 50 to indicate the dosage. There are 50 tablets in each bottle. Additionally, the company made a five-milligram version of Dianabol (methandrostenolone) and a whopping 50-milligram version of Winstrol (stanozolol). These come 100 and 50 tablets to bottle, respectively, all of which are stamped with their respective dosages. Don’t let the less than sparkling looking labels fool you. The company may simply have invested its time and effort more into obtaining raw materials and producing quality steroids than worrying about having a “pretty” appearance. If you find these steroids, rest assured they are legit. If you haven’t noticed, though, I am writing in the past tense for a reason. This month, oxymetholone takes a double hit, and I have the displeasure of reporting that this relatively new and seemingly reputable underground operation has been busted. Alpha Tech oxymetholone therefore gets the thumbs up, but unfortunately you won’t be able to find it on the black market much longer. —WL
When most of us think of the hormones in the body that are responsible for building muscle, usually testosterone, growth hormone (via IGF-1) and insulin come to mind. These are the “big three,” so to speak. By no coincidence, these are the same three hormones we find bodybuilders manipulating levels of or supplementing in various synthetic drug forms to aid in the pursuit of “hugeness.” But, when it comes to understanding the underlying mechanisms involved in muscle growth, there is more to it than just these three hormones. In fact, there is another class of hormonal compounds involved in the regulation of skeletal muscle protein that are necessary for the accumulation of new mass. These hormones are called prostaglandins and they are too often overlooked when it comes to discussions about what is controlling muscle growth in our bodies. As you will see, they are among the most vital components in the stimulation of protein synthesis and the support of skeletal muscle growth, and you couldn’t gain a single ounce of new muscle without them.Prostaglandins are derivatives of fatty acids produced in various tissues in the body including liver, adipose, and smooth and skeletal muscle. They are called prostaglandins, incidentally, because the first hormone labeled as such was isolated in semen back in the 1930s and was thought at the time to be originating from the prostate itself. Some time later, scientists realized how widely distributed hormones of this type are, and they’ve come to identify different prostaglandin compounds, about 20 in all, in almost every tissue of the body. As a group they have varying physiologic actions, such as modulating immune system function, inflammation, temperature, blood platelet aggregation, smooth muscle contraction and protein turnover in skeletal muscle tissue. The latter role is of primary interest to us, of course, and upon close inspection we see clearly that these hormones are much more than just simple peripheral supporters of protein synthesis. They are, in fact, right there at the very core of muscle growth.
Stretch Stimulus
Prostaglandins begin to exert their strong effects on muscle growth immediately following physical exertion. More specifically, it is the stretch stimulus provided by muscle contractions that first triggers the local release of prostaglandins. These, in turn, play a pivotal role in what will be going on in your muscle cells during the following 48 hours or so of recovery. A study published in 1990 in the American Journal of Physiology looked perhaps most closely at the relationship between prostaglandins, protein turnover and physical exercise.[1] In this investigation, various skeletal muscle cell preparations were incubated under stretch stimulus to replicate the damage induced by exercise. Protein turnover, as measured by the incorporation of the labeled amino acid phenylalanine, was quantified.During the first five hours of stimulation, PGE2 and PGF2alpha prostaglandin levels increased 101 and 41percent, respectively. PGE2, shown in other studies to play a role in increasing protein breakdown,[2] returned to normal levels within 24 hours of mechanical stimulation. PGF2, on the other hand, remained elevated for 48 hours and correlated with a 52-98 percent long-term increase in protein synthesis. The study suggests we are seeing the regulation of protein turnover in two different directions by prostaglandins. PGE2 is tied to the damage initially induced by resistance exercise, and PGF2alpha, the subsequent long-term increase in protein synthesis that rebuilds and strengthens muscle tissue.
Prostaglandin Inhibition
It is perhaps easiest to see just how vital prostaglandins are to muscle growth by looking at what happens when we inhibit their production. This was detailed extremely well in a study conducted in 2001 at the University of Arkansas.[3] In this investigation, a group of 24 recreationally active young male subjects were given maximum OTC doses of ibuprofen (1,200mg/day) or acetaminophen (4,000mg/day), or placebo, and subjected to resistance training. These two popular over-the-counter pain relief medications are known to exert their analgesic effects in the body by inhibiting the cyclooxygenase enzyme, which is responsible for prostaglandin production.[4] [5] Amino acid turnover was measured for 24 hours following the bout of exercise, which allowed the investigators to determine what effect, if any, these drugs would have on protein breakdown and synthesis. The results were startling, and would cause any bodybuilder to think twice before popping one of these OTC pain medications again. Both ibuprofen and acetaminophen effectively blunted the normal post-exercise rise in protein synthesis, which was increased 76 percent above baseline in the group taking only the placebo. This study showed us clearly, and for the first time, that the OTC drugs many of us routinely use to combat muscle soreness actually interfere with the basic process of muscle growth. It is almost as if the workout never even happened in the first place!After the stunning results of the first study, a follow-up investigation was conducted to look more closely at the underlying mechanisms in which ibuprofen and acetaminophen were interfering with post-exercise protein synthesis.[6] Every effort was used to replicate the conditions of the first study, including the use of the same exact group of male subjects (24 in total). The same drug and exercise protocols were followed as well, which entailed maximum daily OTC doses of ibuprofen or acetaminophen and 10-14 sets of Cybex machine knee extensions to failure. This time, however, they did not look at changes in protein turnover, probably because they were already established on these men under the same conditions. Instead, they looked at what effect these drugs would have on the levels of those prostaglandins normally thought to play a role in protein turnover. The results probably could have been expected given what we learned from the earlier stretch stimulus study. Both OTC analgesics strongly blunted the normal post-exercise rise in— you guessed it— PGF2alpha. Acetaminophen additionally suppressed levels of PGE2, while Ibuprofen and placebo both did not interfere with PGE2 release. As was the case with the 1990 study, the end results pointed to PGF2alpha as being the prostaglandin most closely tied to the stimulation of post-exercise protein synthesis.
In Closing
The buildup and breakdown of skeletal muscle mass in the human body is controlled by the complex interaction of a myriad of different components too numerous to cover in a single article, and all too vital to the process as a whole to ignore. When it comes to the level of hormonal regulation specifically, however, we still see that there is not one, but several, hormones integral to what is going on. Given the recent attention to the role prostaglandins play in this process, we can say for certain that no discussion about the underlying hormonal controls of muscle growth could be complete without their mention. It’s also worth noting that a synthetic drug form of PGF2alpha, sold in the U.S. as Lutalyse (diniprost), has recently started eking its way into the gym bags and medicine cabinets of bodybuilders across the country. Although a discussion of its implementation, benefits and potential side effects goes well beyond the scope of this article, it can be said that many people have been reporting extremely positive results with this drug. We can likewise expect its use will be well explored as we go further into the twenty-first century. In the end, we see that prostaglandins, or perhaps more specifically PGF2alpha, indeed do deserve a place right next to the “big three” muscle-builders, testosterone, GH and insulin, as without all four of these hormones doing their part, there simply is no muscle growth.
References
[1] Stretch-induced prostaglandins and protein turnover in cultured skeletal muscle. Vandenburgh et al. Am J Physiol v.259 pg.C232-40
[2] Rodemann, Goldberg et al. J Biological Chem 257(4) 1632-38 1982
[3] Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Trappe, White et al. Am J Physiol Endocrinol Metab. 2002 Mar;282(3):E551-6.
[4] Mechanism of acetaminophen inhibition of cyclooxygenase isoforms. Ouellet M, Percival MD. Arch Biochem Biophys 2001 Mar 15;387(2):273-80
[5] Inhibition of cyclooxygenase-1 and -2 by R(-)- and S(+)-ibuprofen. Boneberg EM, Zou MH, Ullrich V. J Clin Pharmacol 1996 Dec;36(12 Suppl):16S-19S
[6] Skeletal muscle PGF(2)(alpha) and PGE(2) in response to eccentric resistance exercise: influence of ibuprofen acetaminophen. Trappe, White et al. J Clin Endocrinol Metab. 2001 Oct;86(10):5067-70.
Black Market Update
The world supply of Oxymetholone took another big hit recently. Hemogenin, which was at one time one of the most popular forms of oxymetholone (Anadrol®) to be imported into the U.S., is no longer being manufactured. This preparation was made by the Brazilian company Sarsa, which licensed the rights to it from Syntex, the world’s first and leading producer of the drug. It was sold in blisters of 10 tablets in both the U.S. and Brazilian markets for a very reasonable price. Apparently, a lot of public attention has been given to anabolic steroids in this country in recent years, and the government felt there was no longer any legitimate medical need to keep the drug around. At one time oxymetholone was readily used for certain anemic conditions, where it was quite successful at increasing red blood cell production due to the action steroids have on erythropoiesis (the process of red blood cell production). The advent of synthetically manufactured erythropoietin (a hormone much more directly tied to blood cell production) made oxymetholone obsolete, however. So the drug remains now in only a few corners of the world where it is either used for HIV+ muscle wasting, or continues to be sold solely because of its popularity with athletes. Pictured here also is an underground generic Anadrol (labeled simply oxymetholone 50) from the firm Alpha Tech. The tablets themselves are light blue in color, and contain an imprinted 50 to indicate the dosage. There are 50 tablets in each bottle. Additionally, the company made a five-milligram version of Dianabol (methandrostenolone) and a whopping 50-milligram version of Winstrol (stanozolol). These come 100 and 50 tablets to bottle, respectively, all of which are stamped with their respective dosages. Don’t let the less than sparkling looking labels fool you. The company may simply have invested its time and effort more into obtaining raw materials and producing quality steroids than worrying about having a “pretty” appearance. If you find these steroids, rest assured they are legit. If you haven’t noticed, though, I am writing in the past tense for a reason. This month, oxymetholone takes a double hit, and I have the displeasure of reporting that this relatively new and seemingly reputable underground operation has been busted. Alpha Tech oxymetholone therefore gets the thumbs up, but unfortunately you won’t be able to find it on the black market much longer. —WL