The argument for AR down-regulation sounds pretty straightforward on the surface. After all, we know that receptor down-regulation happens with other messenger-mediated systems in the body such as adrenergic receptors. It has
been shown that when taking a beta agonist such as Clenbuterol, the number of
beta-receptors on target cells begins to decrease. (This is due to a decrease in the half-life of receptor proteins without a decrease in the rate that the cell is making new receptors.) This leads to a decrease in the potency of a given dose. Subsequently, with fewer receptors you get a smaller, or diminished, physiological response. This is a natural way for your body to maintain equilibrium in the face of an unusually high level of beta-agonism.

In reality this example using Clenbuterol is not an appropriate one. Androgen receptors
and adrenergic receptors are quite different.
Nevertheless, this is the argument for
androgen receptor down-regulation and the reasoning behind it. The differences in the
regulation of ARs and adrenergic receptors in part show the error in the view that AR
down-regulate when you take steroids. Where adrenergic receptor half-life is decreased
in most target cells with increased catecholamines, AR receptors half-live's are actually increased in many tissues in the presence of androgens.1

Let me present a different argument against AR down-regulation in muscle tissue. I feel
that once you consider all of the effects of testosterone on muscle cells you come to
realize that when you eventually stop growing (or grow more slowly) it is not because
there is a reduction in the number of androgen receptors.

Testosterone: A multifaceted anabolic
Consider the question, "How do anabolic steroids produce muscle growth?" If you were to ask the average bodybuilding enthusiast I think you would hear, "steroids increase
protein synthesis." This is true, however there is more to it than simple increases in
protein synthesis. In fact, the answer to the question of how steroids work must include
virtually every mechanism involved in skeletal muscle hypertrophy. These mechanisms
include:

Enhanced protein synthesis

Enhanced protein synthesis

Enhanced growth factor activity (e.g. GH, IGF-1, etc.)

Enhanced activation of myogenic stem cells (i.e. satellite cells)

Enhanced myonuclear number (to maintain nuclear to cytoplasmic ratio)

New myofiber formation

Starting with enhanced growth factor activity, we know that testosterone increases GH and IGF-1 levels. In a study by Fryburg the effects of testosterone and stanozolol were compared for their effects on stimulating GH release.2 Testosterone enanthate (only 3 mg per kg per week) increased GH levels by 22% and IGF-1
levels by 21% whereas oral stanozolol (0.1mg per kg per day) had no effect whatsoever
on GH or IGF-1 levels. This study was only 2-3 weeks long, and although stanozolol did
not effect GH or IGF-1 levels, it had a similar effect on urinary nitrogen
levels.

What does this difference in the effects of testosterone and stanozolol mean? It means
that stanozolol may increase protein synthesis by binding to AR receptors in existing myonuclei, however, because it does not increase growth factor levels it is much less effective at activating satellite cells and therefore may not increase satellite cell activity nor myonuclear number directly when compared to testosterone esters. I will explain the importance of increasing myonuclear number in a moment, first lets look at how increases in GH and IGF-1 subsequent to testosterone use effects
satellite cells.

Don't forget Satellite cells!
Satellite cells are myogenic stem cells, or pre-muscle cells, that serve to assist
regeneration of adult skeletal muscle. Followingproliferation (reproduction) and
subsequent differentiation (to become a specific type of cell), satellite cells will fuse with one another or with the adjacent damaged muscle fiber, thereby increasing the number of myonuclei for fiber growth and repair. Proliferation of satellite cells is necessary in order to meet the needs of thousands of muscle cells all potentially requiring additional nuclei. Differentiation is necessary in order for the new
nucleus to behave as a nucleus of muscle origin. The number of myonuclei directly
determines the capacity of a muscle cell to manufacture proteins, including androgen
receptors.

In order to better understand what is physically happening between satellite cells and muscle cells, try to picture 2 oil droplets floating on water. The two droplets represent a muscle cell and a satellite cell. Because the lipid bilayer of cells are hydrophobic just like common oil droplets, when brought into proximity to one
another in an aqueous environment, they will come into contact for a moment and
then fuse together to form one larger oil droplet. Now whatever was dissolved within
one droplet (i.e. nuclei) will then mix with the contents of the other droplet. This is a
simplified model of how satellite cells donate nuclei, and thus protein-synthesizing
capacity, to existing muscle cells.

Enhanced activation of satellite cells by testosterone requires IGF-1. Those androgens that aromatize are effective at not only increasing IGF-1 levels but also the sensitivity of satellite cells to growth factors.3 This action has no direct effect on protein synthesis, but it does lead to a greater capacity for protein
synthesis by increasing fusion of satellite cells to existing fibers. This increases the
number of myonuclei and therefore the
capacity of the cell to produce proteins. That is why large bodybuilders will benefit significantly more from high levels of androgens compared to a relatively new user.

Testosterone would be much less effective if it were not able to increase myonucleation.
There is finite limit placed on the cytoplasmic/nuclear ratio, or the size of a muscle cell in relation to the number of nuclei it contains.4 Whenever a muscle grows in response to training there is a coordinated increase in the number of
myonuclei and the increase in fiber cross sectional area (CSA). When satellite cells are prohibited from donating viable nuclei, overloaded muscle will not grow.5,6 Clearly,
satellite cell activity is a required step, or prerequisite, in compensatory muscle hypertrophy, for without it, a muscle
simply cannot significantly increase total protein content
or CSA.
More myonuclei mean more receptors So it is not only true that testosterone increases protein synthesis by activating genetic expression, it also increases the capacity of the muscle to grow in the future by leading to the accumulation of myonuclei which are required for protein synthesis. There is good reason to believe that testosterone in high enough doses may even encourage new fiber formation. To quote the authors of a recent study on the effects of steroids on muscle cells:

"Intake of anabolic steroids and strength-training induce an increase in muscle size by both hypertrophy and the formation of new muscle fibers.
We propose that activation of satellite cells is a key process and is enhanced by the
steroid use."7

Simply stated, supraphysiological levels of testosterone give rise to increased numbers of myonuclei and thereby an increase in the number of total androgen receptors per muscle
fiber. Keep in mind that I am referring to testosterone and testosterone esters. Not the
neutered designer androgens that people take to avoid side effects. This is not an
argument to rapidly increase the dosages you use. It takes time for these changes to
occur and the benefits of higher testosterone levels will not be immediately realized.

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What the mind of the man can conceive and believe, it can achieve

WOW!!!

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What the mind of the man can conceive and believe, it can achieve

And Edge, this is a LONG running thing with some of us mods (and a number of members as well). You have the Test camp, and then you have the Other camp. We never miss an opportunity to jab each other on this.

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LAte

It is also against big dosages of test for newbies and also says that big dosages are useless for a beginner.

That's the primary reason why i recommend relatively high (500+mg/week) doses for beginers.

quote:

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This does not mean that all you need is massive doses to get huge. Recruitment of satellite cells and increased myonucleation requires consistent "effective" training, massive amounts of food, and most importantly, time. Start out with reasonable doses. Then, as you get bigger you can adjust your doses upwards.

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This means high dosage are not useful until you have cycled for a while with moderate dosages. Please read carefully as to not argue over a moot point.

Seems as though E2 has been right the whole time.

Check it out my 2on/4off experiment...
http://www.elitefitness.com/ubb/Archives/Forum1/11-2000/037352.html

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What the mind of the man can conceive and believe, it can achieve

So the bottom line is that the more you gain, the harder it is to gain. Just like that max bench - in the beginning the progress is great, but then later, every five pounds is killer.

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LAte