receptor saturation and tren

[BITTAPART2]

lets say someone has been taking a longer estered testosterone like enanthate for around 20 weeks and they feel as if there receptor sites have been saturated. Could that person add tren Ace to this cycle and expect anything or would the saturation factor diminish the effects of tren as well as it does the testosterone????

[BITTAPART2]

im gonna bump this

[Alpha-Male]

i'm gonna say no, it wouldn't help...but i base that purely on speculation...

bump for more insightful response

AM

[symatech]

First let me ask you why or how you know that your receptors are saturated. The AR is dissolved in the cytosol, when it binds to a steroid molecule it goes inside the cell nucleus where it starts making new proteins etc, which in turn make new muscle cells which in turn create more AR. So to say that your AR receptors are saturated is something I find very hard to believe.

I'm guessing your gains have slowed down and you want them to come back and that's why you wish to add tren, am I correct?

[Pinnacle]

First let me ask you why or how you know that your receptors are saturated. The AR is dissolved in the cytosol, when it binds to a steroid molecule it goes inside the cell nucleus where it starts making new proteins etc, which in turn make new muscle cells which in turn create more AR. So to say that your AR receptors are saturated is something I find very hard to believe.

I'm guessing your gains have slowed down and you want them to come back and that's why you wish to add tren, am I correct?

I don't know symatech.I've been on long cycles and growth totally stopped around week 18 or so.I know several other guys that run real long cycle of Test alone,and they don't put on an ounce of muscle after a ceratin period of time.I'd have to say some sort of saturation is taking place.There's def a reason for the halt in growth.What it is exactly,I'm not certain.

~Pinnacle~

[symatech]

I don't know symatech.I've been on long cycles and growth totally stopped around week 18 or so.I know several other guys that run real long cycle of Test alone,and they don't put on an ounce of muscle after a ceratin period of time.I'd have to say some sort of saturation is taking place.There's def a reason for the halt in growth.What it is exactly,I'm not certain.

~Pinnacle~

don't get me wrong, everything in the body tries to maintain homeostasis so down regulation of the AR is possible, I just doubt that's the reason for the lack of gains. Allow me to relate an article which has been posted here several times:

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Receptor Down Regulation

Brian Haycock


There is as much misinformation about steroids as there is good information had among bodybuilding enthusiasts. Go to any gym and you will hear some kid spouting off to his buddies about how steroids do this, or how they do that, or whatever. This soon starts somewhat of a pissing contest (excuse the expression) as to who knows more about steroids. It’s the same kind of titillating and infectious banter that adolescent boys get into about girls and sex. With steroid banter you hear all the popular terms like Deca, Test, GH, gyno, zits, raisins, "h-u-u-u-ge", roid, freak, monster, roid-rage, "I knew this guy once", etc., etc.. If by some rare chance they are smart and have been reading this or some other high quality bodybuilding site on the net, they may actually get a few details right. More often than not they know just enough to be dangerous. Fortunately steroids haven’t proven to be all that dangerous. Not only that, but most of these guys who are infatuated with steroids won’t ever use or even see them except in magazines.

This kind of ego driven gym talk doesn’t really bother me until they begin giving advice to other clueless people who actually have access to them. Spewing out steroid lingo gives other less experienced kids the impression that these kids actually know what they are talking about. That’s how all of the psuedo-science folklore about steroids perpetuates. This is also why most people who actually use steroids know little about them. This last fact should bother anyone who cares about bodybuilding and/or bodybuilders.

I started out with this article planning on giving some textbook style explanation as to why using steroids doesn’t down regulate androgen receptors (AR). Then after considering some of my critics views that I tend to write articles that hardly anyone can read, I decided to write an easy to read, yet informative explanation about what androgens actually do and how this precludes androgen receptor down regulation. I still have a few references but not so many that it looks like a review paper.

Androgen receptors down-regulate….Don’t they?

One misunderstood principle of steroid physiology is the concept of androgen receptors (AR), sometimes called "steroid receptors", and the effects of steroid use on their regulation. It is commonly believed that taking androgens for extended periods of time will lead to what is called AR "down regulation". The premise for this argument is; when using steroids during an extended cycle, you eventually stop growing even though the dose has not decreased. This belief has persisted despite the fact that there is no scientific evidence to date that shows that increased levels of androgens down regulates the androgen receptor in muscle tissue.

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 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…

In part 2 we will discuss the role of satellite cells and myonuclei and how testosterone (androgens) activates these systems to create muscle growth far beyond what simple activation of the androgen receptor can produce.

In part 1 of this article we discussed the mistake of thinking about androgen receptors (testosterone receptors) in the same way we think of other receptors such as beta-receptors. Beta-receptors down regulate in response to beta-adrenergic stimulation whereas there is good evidence that androgen receptors increase in numbers in response to androgens. We also discussed the various affects of testosterone on muscle growth. Testosterone does far more than simply increase the rate of protein synthesis!

Now in part 2 we will finish our discussion of androgen receptor regulation as it pertains to the way muscle cells grow. The very mechanism of real muscle growth opens the door for increased androgen receptor number in response to testosterone treatment.

Don’t forget Satellite cells!

Satellite cells are myogenic stem cells, or pre-muscle cells, that serve to assist regeneration of adult skeletal muscle. Following proliferation (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.

Another group of researchers are quoted as saying:

"…it is intriguing to speculate that the upregulation of AR levels via the administration of pharmacological amounts of androgens might convert some muscles that normally have a minor or no response to muscles with enhanced androgen responsiveness"(8)

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. It does shed some light however on the proportional differences between natural and androgen assisted bodybuilders physiques.

Maintenance of the kind of muscle mass seen in top-level bodybuilders today requires a given level of androgens in the body. That level will vary from individual to individual depending on their genetics. Nevertheless, if the androgen level drops, or if they were to "cycle off" the absolute level of lean mass will also drop. Likewise, as the level of androgens goes up, so will the level of lean mass that individual will be able to maintain. All of this happens without any evidence of AR down regulation. More accurately it demonstrates a relationship between the amount of androgens in the blood stream and the amount of lean mass that you can maintain. 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.

References:

1. Kemppainen JA, Lane MV, Sar M, Wilson EM. Androgen receptor phosphorylation, turnover, nuclear transport, and transcriptional activation. Specificity for steroids and antihormones. J Biol Chem 1992 Jan 15;267(2):968-74

2. Fryburg DA., Weltman A., Jahn LA., et al: Short-term modulation of the androgen milieu alters pulsatile, but not exercise- or growth hormone releasing hormone-stimulated GH secretion in healthy men: Impact of gonadal steroid and GH secretory changes on metabolic outcomes. J Clin Endocrinol. Metab. 82(11):3710-37-19, 1997

3. Thompson SH., Boxhorn LK., Kong W., and Allen RE. Trenbolone alters the responsiveness of skeletal muscle satellite cells to fibroblast growth factor and insulin-like growth factor-I. Endocrinology. 124:2110-2117, 1989

4. Rosenblatt JD, Yong D, Parry DJ., Satellite cell activity is required for hypertrophy of overloaded adult rat muscle. Muscle Nerve 17:608-613, 1994

5. Rosenblatt JD, Parry DJ., Gamma irradiation prevents compensatory hypertrophy of overloaded extensor digitorum longus muscle. J. Appl. Physiol. 73:2538-2543, 1992

6. Phelan JN, Gonyea WJ. Effect of radiation on satellite cell activity and protein expression in overloaded mammalian skeletal muscle. Anat. Rec. 247:179-188, 1997

7. Kadi F, Eriksson A, Holmner S, Thornell LE. Effects of anabolic steroids on the muscle cells of strength-trained athletes. Med Sci Sports Exerc 1999 Nov;31(11):1528-34

8. Antonio J, Wilson JD, George FW. Effects of castration and androgen treatment on androgen-receptor levels in rat skeletal muscles. J Appl Physiol. 1999 Dec;87(6):2016-9.

[punchrf]

I don't know symatech.I've been on long cycles and growth totally stopped around week 18 or so.I know several other guys that run real long cycle of Test alone,and they don't put on an ounce of muscle after a ceratin period of time.I'd have to say some sort of saturation is taking place.There's def a reason for the halt in growth.What it is exactly,I'm not certain.

~Pinnacle~

i don't think that this is entirely true. what about the people on hrt? the effects diminish but will still be there. if you stop growing completely during a cycle it sounds like you need to up the calories or mix up the workouts. but also if your gains are halting at a certain point then that would be a good length for you to stop cycles at. everyones different though. i made most of my gains in the last 4-5 weeks before i stopped my last 22 week cycle, but then again i upped the test also because i didn't want to get small gains. the sickness in the start of the last cycle didn't help me either.

[shortie]

Good article-thanks for puttin it up Symatech.

[Pinnacle]

i don't think that this is entirely true. what about the people on hrt? the effects diminish but will still be there. if you stop growing completely during a cycle it sounds like you need to up the calories or mix up the workouts. but also if your gains are halting at a certain point then that would be a good length for you to stop cycles at. everyones different though. i made most of my gains in the last 4-5 weeks before i stopped my last 22 week cycle, but then again i upped the test also because i didn't want to get small gains. the sickness in the start of the last cycle didn't help me either.

I disagree.I've ran HRT doses more than once.They are maintenance doses.You don't grow on HRT.I have way more cycles under my belt than I care to admit.It's not the training,cals,or dose.There's more to it than that.I don't have time right now to read the article posted.I'll get to that later.

~Pinnacle~

[symatech]

I disagree.I've ran HRT doses more than once.They are maintenance doses.You don't grow on HRT.I have way more cycles under my belt than I care to admit.It's not the training,cals,or dose.There's more to it than that.I don't have time right now to read the article posted.I'll get to that later.

~Pinnacle~

there is an article or study which does promote the idea of ar down regulation, I have been having trouble finding it though. I like to post all sides of the issues so I'll keep looking.

[punchrf]

I disagree.I've ran HRT doses more than once.They are maintenance doses.You don't grow on HRT.I have way more cycles under my belt than I care to admit.It's not the training,cals,or dose.There's more to it than that.I don't have time right now to read the article posted.I'll get to that later.

~Pinnacle~

i've known people that stay on year round and make consistent gains all year. i've also known some that are also on year round but have gains stop or diminish as you stated. i think that genetics among other reasons are the culprit but there is just to many variables to pin point one. you found what works for you so go with it. by your stats in your profile it sounds like it's working well for you. everyones different. i usually can get my growth to go quite awhile into cycle by adding more sets to my workouts or increasing calories but i have always been able to put on weight fairly easily, it's the fat coming off thats tough for me.

[Drummerboy]

test is known to increase receptor sites, and if you add tren it will only compete for receptors, not make more. tren is also very androgenic in many tissues, and works awsome for strength/hardness. If your plateau'd on your test, adding tren will up your weights, reps and harden up your gains for sure. starting at 50-75 mg ed really, really works. max 100 a day for me...

[Drummerboy]

I don't know symatech.I've been on long cycles and growth totally stopped around week 18 or so.I know several other guys that run real long cycle of Test alone,and they don't put on an ounce of muscle after a ceratin period of time.I'd have to say some sort of saturation is taking place.There's def a reason for the halt in growth.What it is exactly,I'm not certain.

~Pinnacle~

i dont have studies, but i can say from experience that when i reach a certain weight, usually according to the size of my dose, i stop growing. I think your body will quickly get to the size you will be according to dose, then slow down. this has been the case with every cycle ive ever done. Fast esters, like Prop and NPP put on gains SO fast, and stop gaining after about 6 weeks, maybe less for me. I then ramp up till the end, say week 10-12 for short esters or 16 for long esters... just my experience though

[Drummerboy]

just to be clear about my previous post... if im on say 700mg prop a week, with 500 tren... i grow real fast for 3 weeks. then, week 4 and 5 slow, then i plateau. Doesnt matter how hard i train, mix it up, or eat more. I will only get marginal gains after this point. On this dose, i can hit like 215 fairly lean... then stop dead... i up my dose, eat more accordingly, i ALWAYS mix up my gym routines, and i start to gain again... i really thing the upper plateau is dose dependant...

[BITTAPART2]

I couldnt agree more drummerboy, a lot of people are anti higher doses after a plateau, and I will admit it is probably the wiser thing to not do it when taking your overall health into consideration, although IMO it will produce more gains when combined w/ a caloric increase, in fact this is a whole other topic but if those calories are upped in the way of carbs rather than upping protien, the benefits are far greater.