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DJ_UFO
Banned
SKELETAL MUSCLE HYPERTROPHY
By Karl Hoffman
Old models and new with an emphasis on DHT
The traditional model of androgen stimulated muscle hypertrophy posits that androgens enter the muscle cell and activate genes coding for proteins such as the contractile protein myosin. While not questioned, a new model has emerged in which androgens drive adult stem cells (cells capable of maturing into varied tissue such as bone, muscle or fat cells) away from an adipocytic lineage towards becoming muscle tissue. This neatly explains how androgens and anabolic steroids reduce fat mass and build lean mass simultaneously.
A new "prohormone" to hit the market (ironically only shortly before the prohormone ban takes effect is an oral version of dihydrotestosterone, or methyl-DHT. What role if any does DHT play in the development of strength and muscle hypertrophy?
According to the traditional view, DHT is rendered inactive by intracellular enzymes shortly upon entering muscle tissue. Therefore it has little capability to stimulate protein synthesis. However, in the new paradigm (bear in mind that the old and new views of androgen action are not at odds with each other, but rather are complementary) DHT, like its parent compound testosterone, is fully capable of promoting the conversion of stem cells to adult muscle tissue and at much smaller concentrations than testosterone (1).
One action of DHT that may play an important role in this transformation process is the observed upregulation of the androgen receptor in muscle satellite cells when exposed to supraphysiological levels of DHT (as well as testosterone). Satellite cells are muscle precursor cells derived from stem cells that lie further along the path to myogenesis than do stem cells (2).
it is fully capable of demonstrating anabolism in the stem cell model of muscle growth
So while DHT may not exert an anabolic effect in the classical model of androgen induced protein synthesis, it is fully capable of demonstrating anabolism in the stem cell model of muscle growth.
Much is often made of the strength enhancing effects of DHT as well. In animals, exposure to androgenic steroids, but not estrogenic ones increase the size of motoneurons. Aromatization is not important to this process, so it may be one factor involved in the strength gains reported by DHT users (3).
Note however that in all the cases described above, testosterone exerts the same or nearly the same effect as does DHT, except for testosterone’s ability to directly stimulate protein synthesis in muscle.
Note also that numerous studies in humans have demonstrated that DHT is capable of suppressing endogenous testosterone production. For this reason, and the fact that DHT seems not to be able to stimulate muscle protein synthesis, it would not seem reasonable to employ DHT or the oral version methyl-DHT as a stand alone anabolic/androgenic agent.
Where its usefulness would seem to lie is in use in conjunction with other suppressive anabolic steroids or prohormones. In this case we reap the benefits of DHT as described above, while preserving the increase in protein synthesis associated with other anabolic agents such as nandrolone or its prohormone precursor. Since these other agents suppress the HPTA in any case, any additional suppression by oral DHT would seem to be moot.
There may or not be health issues involved with DHT use at least as far as the prostate is concerned. This is a hotly debated area of research. Many
but what is known is that DHT directly antagonizes the estrogen receptor as well as acting as an aromatase inhibitor
researchers believe that the intraprostatic conversion of testosterone to DHT is more important than circulating levels of DHT, and that by suppressing natural testosterone production exogenous DHT may even exert a beneficial effect on the prostate. Moreover, the role estrogens play in the development of benign prostatic hyperplasia and prostate cancer is debated, but what is known is that DHT directly antagonizes the estrogen receptor (4) as well as acting as an aromatase inhibitor (5).
DHT has also been claimed to stimulate penile erections. While the evidence for this is equivocal in man, in rats DHT does appear to be the active androgen involved in nitric oxide maintained penile erection (6).
So in summary we see as with all androgens and anabolic steroids or their prohormone precursors there are both potential positive and negative effects that should be carefully examined and weighed against each other before using any of these agents.
References Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology. 2003 Nov;144(11):5081-8
Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S. Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment. J Clin Endocrinol Metab. 2004 Oct;89(10):5245-55
Jordan CL, Watamura S, Arnold AP. Androgenic, not estrogenic, steroids alter neuromuscular synapse elimination in the rat levator ani. Brain Res Dev Brain Res. 1995 Feb 16;84(2):215-24.
Mooradian AD, Morley JE, Korenman SG. Biological actions of androgens. Endocr Rev. 1987 Feb;8(1):1-28
Perel E, Stolee KH, Kharlip L, Blackstein ME, Killinger DW The intracellular control of aromatase activity by 5 alpha-reduced androgens in human breast carcinoma cells in culture. J Clin Endocrinol Metab 1984 Mar;58(3):467-72
Lugg JA, Rajfer J, Gonzalez-Cadavid NF. Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat Endocrinology 1995 Apr;136(4):1495-501
By Karl Hoffman
Old models and new with an emphasis on DHT
The traditional model of androgen stimulated muscle hypertrophy posits that androgens enter the muscle cell and activate genes coding for proteins such as the contractile protein myosin. While not questioned, a new model has emerged in which androgens drive adult stem cells (cells capable of maturing into varied tissue such as bone, muscle or fat cells) away from an adipocytic lineage towards becoming muscle tissue. This neatly explains how androgens and anabolic steroids reduce fat mass and build lean mass simultaneously.
A new "prohormone" to hit the market (ironically only shortly before the prohormone ban takes effect is an oral version of dihydrotestosterone, or methyl-DHT. What role if any does DHT play in the development of strength and muscle hypertrophy?
According to the traditional view, DHT is rendered inactive by intracellular enzymes shortly upon entering muscle tissue. Therefore it has little capability to stimulate protein synthesis. However, in the new paradigm (bear in mind that the old and new views of androgen action are not at odds with each other, but rather are complementary) DHT, like its parent compound testosterone, is fully capable of promoting the conversion of stem cells to adult muscle tissue and at much smaller concentrations than testosterone (1).
One action of DHT that may play an important role in this transformation process is the observed upregulation of the androgen receptor in muscle satellite cells when exposed to supraphysiological levels of DHT (as well as testosterone). Satellite cells are muscle precursor cells derived from stem cells that lie further along the path to myogenesis than do stem cells (2).
it is fully capable of demonstrating anabolism in the stem cell model of muscle growth
So while DHT may not exert an anabolic effect in the classical model of androgen induced protein synthesis, it is fully capable of demonstrating anabolism in the stem cell model of muscle growth.
Much is often made of the strength enhancing effects of DHT as well. In animals, exposure to androgenic steroids, but not estrogenic ones increase the size of motoneurons. Aromatization is not important to this process, so it may be one factor involved in the strength gains reported by DHT users (3).
Note however that in all the cases described above, testosterone exerts the same or nearly the same effect as does DHT, except for testosterone’s ability to directly stimulate protein synthesis in muscle.
Note also that numerous studies in humans have demonstrated that DHT is capable of suppressing endogenous testosterone production. For this reason, and the fact that DHT seems not to be able to stimulate muscle protein synthesis, it would not seem reasonable to employ DHT or the oral version methyl-DHT as a stand alone anabolic/androgenic agent.
Where its usefulness would seem to lie is in use in conjunction with other suppressive anabolic steroids or prohormones. In this case we reap the benefits of DHT as described above, while preserving the increase in protein synthesis associated with other anabolic agents such as nandrolone or its prohormone precursor. Since these other agents suppress the HPTA in any case, any additional suppression by oral DHT would seem to be moot.
There may or not be health issues involved with DHT use at least as far as the prostate is concerned. This is a hotly debated area of research. Many
but what is known is that DHT directly antagonizes the estrogen receptor as well as acting as an aromatase inhibitor
researchers believe that the intraprostatic conversion of testosterone to DHT is more important than circulating levels of DHT, and that by suppressing natural testosterone production exogenous DHT may even exert a beneficial effect on the prostate. Moreover, the role estrogens play in the development of benign prostatic hyperplasia and prostate cancer is debated, but what is known is that DHT directly antagonizes the estrogen receptor (4) as well as acting as an aromatase inhibitor (5).
DHT has also been claimed to stimulate penile erections. While the evidence for this is equivocal in man, in rats DHT does appear to be the active androgen involved in nitric oxide maintained penile erection (6).
So in summary we see as with all androgens and anabolic steroids or their prohormone precursors there are both potential positive and negative effects that should be carefully examined and weighed against each other before using any of these agents.
References Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology. 2003 Nov;144(11):5081-8
Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S. Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment. J Clin Endocrinol Metab. 2004 Oct;89(10):5245-55
Jordan CL, Watamura S, Arnold AP. Androgenic, not estrogenic, steroids alter neuromuscular synapse elimination in the rat levator ani. Brain Res Dev Brain Res. 1995 Feb 16;84(2):215-24.
Mooradian AD, Morley JE, Korenman SG. Biological actions of androgens. Endocr Rev. 1987 Feb;8(1):1-28
Perel E, Stolee KH, Kharlip L, Blackstein ME, Killinger DW The intracellular control of aromatase activity by 5 alpha-reduced androgens in human breast carcinoma cells in culture. J Clin Endocrinol Metab 1984 Mar;58(3):467-72
Lugg JA, Rajfer J, Gonzalez-Cadavid NF. Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat Endocrinology 1995 Apr;136(4):1495-501
