- Jun 25, 2006
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Androgen Receptor Concentrations
Effects of Exercise and AAS
By definition a hormone is a chemical messenger that’s produced in one organ of the body, and is carried by the blood to others so that it may exert its activity. To do this, it needs to attach to a cellular target, or more specifically a “receptor site.” The receptor enables the hormone to be very specific in its actions, as it will be found only in those cells that need such stimulation. The number of receptor sites in a given cell can also be influenced in various ways, making the body capable of not only regulating where a hormone can exert its activity, but also how much. The concentration of androgen receptors in our muscle cells will, likewise, be important in determining how effective anabolic steroid administration will be. With this in mind, I thought it would be interesting to take an up-close look at two factors that strongly influence androgen receptor density: Exercise and the administration of anabolic steroids themselves. As you will see, these two factors have a strong impact on the body’s sensitivity to anabolic stimulus, perhaps much more so than you realized before.
Exercise
The physiological response to exercise is quite complex, and involves the interaction of numerous systems, all of which are necessary to the process of growth as a whole. It would, likewise, be incorrect to say any one factor was “the” cause of growth. Nonetheless, we can still point out some significant changes that result from exercise that would seem strongly related to muscle hypertrophy. One such factor involves the effect exercise has on cellular androgen receptor concentrations. Or to be more specific, there is an upregulation of receptor density that occurs in muscle cells in direct response to weight-lifting exercise. Such changes make cells much more responsive (sensitive) to testosterone and its related derivatives (steroids), greatly facilitating the anabolic (muscle-building) actions of these hormones. This fact is well-supported in a study published about two years ago, which looked at the effects of resistance exercise on local (muscle) IGF-1 levels in a group of 10 adult subjects.[1] Researchers wanted to know what effect weight-training stimulus would have on the local availability of IGF-1, a hormone known to be an important regulator of muscle growth. To check for androgen involvement (several studies suggest a link between androgen levels and local IGF-1 release), researchers measured changes in both testosterone levels and muscle androgen receptor density. The experiment also involved the separation of eccentric and concentric movements, so that the relative influence of each type of exercise could be considered separately. What resulted was quite interesting. Resistance training caused a 63 percent and 102 percent increase in skeletal muscle androgen receptor concentrations for the eccentric and concentric movements, respectively. IGF-1 levels were notably elevated during the study, while testosterone levels tended to fall slightly. The data did suggest a link between androgenic stimulation and IGF-1 release, but it would have been mediated through changes is androgen receptor concentrations instead of actual hormone levels.
AAS Use
Most of us are used to the explanation that hormones downregulate (lower) their own receptor site concentrations, as some type of intrinsic safety mechanism against overstimulation. When we take a particular drug for long durations, we usually expect that it will have a weaker effect over time. You may be familiar first-hand with the diminishing responsiveness that seems to occur rather quickly with the fat-loss agent clenbuterol, for example. Down regulation of beta-2 receptors is the cause of this phenomenon.[2] Otherwise, a given dose of clenbuterol would probably sustain thermogenesis much longer than the mere few weeks it does now. But, when it comes to anabolic steroids, receptor downregulation is not exactly what happens. In fact, it turns out that androgens actually tend to upreglate (increase) the concentrations of their own receptor sites, not decrease them. Higher concentrations of androgens in the blood therefore lead to increases in the density of receptors in muscle cells! You may be calling me crazy right now, but please don’t rip my article out of the magazine and tear it up just yet. With a little review of the literature you will see that the phenomenon is very well substantiated.For example, a study was published back in 1999, which looked at the anabolic effects of the oral steroid oxandrolone.[3] The study involved administering oxandrolone (15 milligrams per day) to a group of six healthy men for a period of five days. The researchers examined not only changes in protein synthesis and breakdown rates, but also what effect the drug would have on the number of androgen receptors present in muscle cells. The result was a striking increase in both protein synthesis rates and cellular androgen receptor concentrations (breakdown rates were unaffected). An analysis of the muscle biopsy data suggests that androgen receptor levels were approximately doubled during the course of the study. Researchers made note of several studies linking androgen receptor levels to muscle hypertrophy, commenting that in this case some of the enhanced protein synthesizing ability of muscle cells in response to oxandrolone was likely caused by enhanced concentrations of androgen receptors. Further studies with injectable testosterone show a similar result, with doses sufficient to increase androgens to physiological or even supraphysiological levels in older men causing significant elevations in androgen receptor concentrations compared to pretreated levels.[4]
Exercise/Androgen Synergy
When it comes to the combined effects of exercise and anabolic steroid administration on receptor concentrations, a strong synergy is likely to exist between the two. This seems to be supported by a recent study looking at the effects of steroids and exercise in the skeletal muscles of adult and aged rats.[5] The investigation involved the weekly administration of nandrolone decanoate at a dose of six milligrams per kilogram of weight (about 360 milligrams weekly for a 200-pound rat), alone or combined with overload stimulus (involving the surgical removal of supportive muscle tissue causing a much greater load to be placed on the muscle in question). In adult plantaris muscle (comprised primarily of fast-twitch fibers), combined overload and steroid administration increased androgen receptor concentrations three times above that achieved with nandrolone decanoate alone (nine times greater than control animals in total). The greatest result in this study was noted in the soleus muscle (comprised primarily of slow-twitch fibers) of aged rats, where the combined effects of overload and nandrolone decanoate increased androgen receptor levels an incredible 27 times above control values! I think there should be little doubt that a 27-fold, or even nine-fold, increase in AR density would directly and dramatically affect the growth rate of muscle tissue.
In Closing
As you can see, the control of androgen receptor density is in many regards the “other half of the puzzle” when it comes to anabolic steroids. It’s an often-overlooked variable that has as much to do with the effectiveness of a particular drug as the actual blood level of the substance itself. In reviewing the research concerning androgen receptor proliferation, we find that exercise and steroid dose both positively influence receptor density. As a result, both will strongly increase cell sensitivity to the anabolic actions of steroids. Further evidence suggests that a strong synergy exists between the two, such that combined training and steroid administration create a cell much more primed for the actions of androgenic hormones than either is capable of alone. This is perhaps one reason explaining why training is always a necessity for any type of serious growth, even with the use of steroids, or why dramatic (seemingly “unnatural”) changes in body composition often accompany intense resistance exercise and anabolic steroid use.
References
[1] Mechanical load increases muscle IGF-1 and androgen receptor mRNA concentrations in humans. Bamman, Shipp et al. Am J Physiol. Endocrinol. Metab. 280: E383-90 2001
[2] Differential effects of dexamethasone and clenbuterol on rat growth and on beta2-adrenoceptors in lung and skeletal muscle. Huang H, Gazzola C, Pegg GG, Sillence MN. J Anim Sci 2000 Mar;78(3):604-8
[3] Short-term oxandrolone administration stimulated net protein synthesis in young men. Sheffield-Moore et al. J Clin Endocrinol Metab 84(8) 2705-11 (1999)
[4] Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Ferrando, Sheffield-Moore et al. Am J Physiol Endocrinol Metab 2002 Mar;282(3):E601-7
[5] Overload-induced androgen receptor expression in the aged rat hindlimb receiving nandrolone decanoate. Lee, McClung et al. J Appl. Physiol. 94 1153-61 2003.
Black Market Update
This month I’d like to highlight a new addition to the growing global steroid-manufacturing industry, British Dragon. Pictured here is their Boldabol product, a 200mg/ml injectable boldenone undecylenate. Boldabol comes in a clear 10ml vial, with a security hologram sticker (depicting the image of a dragon) affixed to the side of the label to deter counterfeiting. In addition, Dragon makes several other injectables including Durabol (100mg/ml nandrolone phenylpropionate), Trenabol (75 mg/ml trenbolone acetate), Testabol Propionate (100 mg/ml testosterone propionate) and Testabol Depot (200 mg/ml testosterone cypionate). In addition, they make a variety of oral steroids including Oxanabol (5 mg oxandrolone), Stanabol (5 mg and 50 mg stanozolol) and Parabolan Tablets (20mg trenbolone acetate). Reportedly they are working on expanding their line even further in the near future. The feedback on the Dragon products so far has been excellent, suggesting this is a very good company to come across when shopping. Definitely recommended. Just be sure the products carry a security hologram sticker, which are now placed on all items.
Also pictured this month is another in a long line of fake American steroids. This is supposedly a high-dosed testosterone propionate injectable, containing 100mg/ml of steroid; the upper limit of what you find with a human testosterone propionate product. Only a couple veterinary companies have ventured upwards of this dosage, and they needed to use a lot of alcohol to do it, as testosterone propionate is not soluble enough in oil to exceed the 100mg/ml mark. This product also comes in a nice fat 30 ml vial, which should raise suspicion, as vials this size were pretty rare even when companies in the U.S. were manufacturing testosterone propionate (they are not now). Furthermore, the company duplicated here, Geneva Pharmaceuticals, no longer even makes any anabolic steroid products in the U.S.
Needless to say, this product immediately sticks out like a sore thumb. I don’t think I have to tell you to avoid all testosterone propionate products originating in the U.S. at this point, or probably even all U.S. steroid products completely, for that matter. Real American steroid products are a complete rarity now, and the few items still being manufactured are so scarcely diverted to the black market that your chance of finding them would be the equivalent of winning the steroid lottery. –WL
Effects of Exercise and AAS
By definition a hormone is a chemical messenger that’s produced in one organ of the body, and is carried by the blood to others so that it may exert its activity. To do this, it needs to attach to a cellular target, or more specifically a “receptor site.” The receptor enables the hormone to be very specific in its actions, as it will be found only in those cells that need such stimulation. The number of receptor sites in a given cell can also be influenced in various ways, making the body capable of not only regulating where a hormone can exert its activity, but also how much. The concentration of androgen receptors in our muscle cells will, likewise, be important in determining how effective anabolic steroid administration will be. With this in mind, I thought it would be interesting to take an up-close look at two factors that strongly influence androgen receptor density: Exercise and the administration of anabolic steroids themselves. As you will see, these two factors have a strong impact on the body’s sensitivity to anabolic stimulus, perhaps much more so than you realized before.
Exercise
The physiological response to exercise is quite complex, and involves the interaction of numerous systems, all of which are necessary to the process of growth as a whole. It would, likewise, be incorrect to say any one factor was “the” cause of growth. Nonetheless, we can still point out some significant changes that result from exercise that would seem strongly related to muscle hypertrophy. One such factor involves the effect exercise has on cellular androgen receptor concentrations. Or to be more specific, there is an upregulation of receptor density that occurs in muscle cells in direct response to weight-lifting exercise. Such changes make cells much more responsive (sensitive) to testosterone and its related derivatives (steroids), greatly facilitating the anabolic (muscle-building) actions of these hormones. This fact is well-supported in a study published about two years ago, which looked at the effects of resistance exercise on local (muscle) IGF-1 levels in a group of 10 adult subjects.[1] Researchers wanted to know what effect weight-training stimulus would have on the local availability of IGF-1, a hormone known to be an important regulator of muscle growth. To check for androgen involvement (several studies suggest a link between androgen levels and local IGF-1 release), researchers measured changes in both testosterone levels and muscle androgen receptor density. The experiment also involved the separation of eccentric and concentric movements, so that the relative influence of each type of exercise could be considered separately. What resulted was quite interesting. Resistance training caused a 63 percent and 102 percent increase in skeletal muscle androgen receptor concentrations for the eccentric and concentric movements, respectively. IGF-1 levels were notably elevated during the study, while testosterone levels tended to fall slightly. The data did suggest a link between androgenic stimulation and IGF-1 release, but it would have been mediated through changes is androgen receptor concentrations instead of actual hormone levels.
AAS Use
Most of us are used to the explanation that hormones downregulate (lower) their own receptor site concentrations, as some type of intrinsic safety mechanism against overstimulation. When we take a particular drug for long durations, we usually expect that it will have a weaker effect over time. You may be familiar first-hand with the diminishing responsiveness that seems to occur rather quickly with the fat-loss agent clenbuterol, for example. Down regulation of beta-2 receptors is the cause of this phenomenon.[2] Otherwise, a given dose of clenbuterol would probably sustain thermogenesis much longer than the mere few weeks it does now. But, when it comes to anabolic steroids, receptor downregulation is not exactly what happens. In fact, it turns out that androgens actually tend to upreglate (increase) the concentrations of their own receptor sites, not decrease them. Higher concentrations of androgens in the blood therefore lead to increases in the density of receptors in muscle cells! You may be calling me crazy right now, but please don’t rip my article out of the magazine and tear it up just yet. With a little review of the literature you will see that the phenomenon is very well substantiated.For example, a study was published back in 1999, which looked at the anabolic effects of the oral steroid oxandrolone.[3] The study involved administering oxandrolone (15 milligrams per day) to a group of six healthy men for a period of five days. The researchers examined not only changes in protein synthesis and breakdown rates, but also what effect the drug would have on the number of androgen receptors present in muscle cells. The result was a striking increase in both protein synthesis rates and cellular androgen receptor concentrations (breakdown rates were unaffected). An analysis of the muscle biopsy data suggests that androgen receptor levels were approximately doubled during the course of the study. Researchers made note of several studies linking androgen receptor levels to muscle hypertrophy, commenting that in this case some of the enhanced protein synthesizing ability of muscle cells in response to oxandrolone was likely caused by enhanced concentrations of androgen receptors. Further studies with injectable testosterone show a similar result, with doses sufficient to increase androgens to physiological or even supraphysiological levels in older men causing significant elevations in androgen receptor concentrations compared to pretreated levels.[4]
Exercise/Androgen Synergy
When it comes to the combined effects of exercise and anabolic steroid administration on receptor concentrations, a strong synergy is likely to exist between the two. This seems to be supported by a recent study looking at the effects of steroids and exercise in the skeletal muscles of adult and aged rats.[5] The investigation involved the weekly administration of nandrolone decanoate at a dose of six milligrams per kilogram of weight (about 360 milligrams weekly for a 200-pound rat), alone or combined with overload stimulus (involving the surgical removal of supportive muscle tissue causing a much greater load to be placed on the muscle in question). In adult plantaris muscle (comprised primarily of fast-twitch fibers), combined overload and steroid administration increased androgen receptor concentrations three times above that achieved with nandrolone decanoate alone (nine times greater than control animals in total). The greatest result in this study was noted in the soleus muscle (comprised primarily of slow-twitch fibers) of aged rats, where the combined effects of overload and nandrolone decanoate increased androgen receptor levels an incredible 27 times above control values! I think there should be little doubt that a 27-fold, or even nine-fold, increase in AR density would directly and dramatically affect the growth rate of muscle tissue.
In Closing
As you can see, the control of androgen receptor density is in many regards the “other half of the puzzle” when it comes to anabolic steroids. It’s an often-overlooked variable that has as much to do with the effectiveness of a particular drug as the actual blood level of the substance itself. In reviewing the research concerning androgen receptor proliferation, we find that exercise and steroid dose both positively influence receptor density. As a result, both will strongly increase cell sensitivity to the anabolic actions of steroids. Further evidence suggests that a strong synergy exists between the two, such that combined training and steroid administration create a cell much more primed for the actions of androgenic hormones than either is capable of alone. This is perhaps one reason explaining why training is always a necessity for any type of serious growth, even with the use of steroids, or why dramatic (seemingly “unnatural”) changes in body composition often accompany intense resistance exercise and anabolic steroid use.
References
[1] Mechanical load increases muscle IGF-1 and androgen receptor mRNA concentrations in humans. Bamman, Shipp et al. Am J Physiol. Endocrinol. Metab. 280: E383-90 2001
[2] Differential effects of dexamethasone and clenbuterol on rat growth and on beta2-adrenoceptors in lung and skeletal muscle. Huang H, Gazzola C, Pegg GG, Sillence MN. J Anim Sci 2000 Mar;78(3):604-8
[3] Short-term oxandrolone administration stimulated net protein synthesis in young men. Sheffield-Moore et al. J Clin Endocrinol Metab 84(8) 2705-11 (1999)
[4] Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Ferrando, Sheffield-Moore et al. Am J Physiol Endocrinol Metab 2002 Mar;282(3):E601-7
[5] Overload-induced androgen receptor expression in the aged rat hindlimb receiving nandrolone decanoate. Lee, McClung et al. J Appl. Physiol. 94 1153-61 2003.
Black Market Update
This month I’d like to highlight a new addition to the growing global steroid-manufacturing industry, British Dragon. Pictured here is their Boldabol product, a 200mg/ml injectable boldenone undecylenate. Boldabol comes in a clear 10ml vial, with a security hologram sticker (depicting the image of a dragon) affixed to the side of the label to deter counterfeiting. In addition, Dragon makes several other injectables including Durabol (100mg/ml nandrolone phenylpropionate), Trenabol (75 mg/ml trenbolone acetate), Testabol Propionate (100 mg/ml testosterone propionate) and Testabol Depot (200 mg/ml testosterone cypionate). In addition, they make a variety of oral steroids including Oxanabol (5 mg oxandrolone), Stanabol (5 mg and 50 mg stanozolol) and Parabolan Tablets (20mg trenbolone acetate). Reportedly they are working on expanding their line even further in the near future. The feedback on the Dragon products so far has been excellent, suggesting this is a very good company to come across when shopping. Definitely recommended. Just be sure the products carry a security hologram sticker, which are now placed on all items.
Also pictured this month is another in a long line of fake American steroids. This is supposedly a high-dosed testosterone propionate injectable, containing 100mg/ml of steroid; the upper limit of what you find with a human testosterone propionate product. Only a couple veterinary companies have ventured upwards of this dosage, and they needed to use a lot of alcohol to do it, as testosterone propionate is not soluble enough in oil to exceed the 100mg/ml mark. This product also comes in a nice fat 30 ml vial, which should raise suspicion, as vials this size were pretty rare even when companies in the U.S. were manufacturing testosterone propionate (they are not now). Furthermore, the company duplicated here, Geneva Pharmaceuticals, no longer even makes any anabolic steroid products in the U.S.
Needless to say, this product immediately sticks out like a sore thumb. I don’t think I have to tell you to avoid all testosterone propionate products originating in the U.S. at this point, or probably even all U.S. steroid products completely, for that matter. Real American steroid products are a complete rarity now, and the few items still being manufactured are so scarcely diverted to the black market that your chance of finding them would be the equivalent of winning the steroid lottery. –WL