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  1. #1
    FirstTimeRage's Avatar
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    Receptor downregualtion/ upregulation

    hey guys im just curious after a cycle of test and tren , how long would it take to have your receptors upregulate?

    in other words, assuming that one does not concider the negative effects of being on gear much too soon after PCT, how long should he wait?

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    ^^^ i think one of the neg effects of going on too soon after pct IS not allowing receptors to upregulate fully ..so in that context your question is a little off i think....

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    I do think you should “consider the negative effects of being on gear much too soon after PCT” before jumping on to an other cycle but to answer your question:

    I’ve done a fair bit of research and not found any convincing evidence of receptor down regulation.

    There is a very strong argument it does not even exist so with that being said you could get on a cycle as soon as you like (many people run back to back cycles, there is one guy on the board keep a very interesting log of his 18month cycle)

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    ^^^ mmm i cant speak directly to anabolics and recptor down regulation. I can however, based on what I do for a living, state it is a very real issue and concern when it comes to a great % of pharmaceutical medications. The continuing need to increase dosages of certain meds because of this is an ongoing area of concern because many medications ,to a certain degree, are toxic or exhibit increased unwanted side effects as dosages increase. Anyway....i'm not so sure about it being of no concern ...based on steroids mechanism of action in the body (receptor site binding) ...i would more wonder how long it takes....
    Last edited by jimmyinkedup; 12-05-2008 at 03:37 PM.

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    Quote Originally Posted by graeme87 View Post
    I do think you should “consider the negative effects of being on gear much too soon after PCT” before jumping on to an other cycle but to answer your question:

    I’ve done a fair bit of research and not found any convincing evidence of receptor down regulation.

    There is a very strong argument it does not even exist so with that being said you could get on a cycle as soon as you like (many people run back to back cycles, there is one guy on the board keep a very interesting log of his 18month cycle)
    thanks for the info, do you have any sources i could read on that? anything i google seems irrelevant.

    so assuming i started my next cycle 2 weeks following my PCT would i notice any reduction in gains? through other mechanisms other then down regulation of the receptors?

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    Mulciber is offline Scammer
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    your not concerned about recovery of HPTA before jumping back on...
    have any bloodwork done?

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    *L* I love it ...wait till someone gives the answer you want to hear...latch on to that ...and ask that person for reassurance...... who needs bloodwork???? dude on board said its cool ...oh brother....

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    ^^ thats always how it goes..

    i agree with your point of meds, but i think for steroids they are still so much more powerful than lifting naturally you won't really see the effects right away, so like you said, the time it takes is more the question.

    so if you go 500mg tren + 500mg test back to back (theoretically) you might gain like 12 pounds the first time and 10 the next. so no one will really complain with 10 pounds but it is a slight decrease.

    also, why even bother with a pct if you're going to shut yourself down again right away? very illogical..

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    Mulciber is offline Scammer
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    Quote Originally Posted by jimmyinkedup View Post
    *L* I love it ...wait till someone gives the answer you want to hear...latch on to that ...and ask that person for reassurance...... who needs bloodwork???? dude on board said its cool ...oh brother....
    LMAO.. sometimes you just gotta say WTF

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    MuscleScience is online now AR-Hall of Famer
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    Quote Originally Posted by jimmyinkedup View Post
    ^^^ mmm i cant speak directly to anabolics and recptor down regulation. I can however, based on what I do for a living, state it is a very real issue and concern when it comes to a great % of pharmaceutical medications. The continuing need to increase dosages of certain meds because of this is an ongoing area of concern because many medications ,to a certain degree, are toxic or exhibit increased unwanted side effects as dosages increase. Anyway....i'm not so sure about it being of no concern ...based on steroids mechanism of action in the body (receptor site binding) ...i would more wonder how long it takes....
    This is a response to a question in my Q@A thread about drug tolerance:

    The body has a mechanism that can render drugs inactive. If you think about it anytime you put something in your body you disrupt its normal physiology. The body wants to be in its normal operating range. The Liver specifically expresses a family of enzymes commonly know as the cytochrome P450 oxidases (CYP). This group of enzymes is very diverse and has important functions.

    When the body is exposed to a compound lets call it compound X. The body reacts to it by up regulating the expression of CYP that is specific to that compound. CYP will react with compound X rendering it chemically inactive. Usually by oxidizing the compound which is known as Phase I metabolism by pharmacologist. This leads to drug tolerance which requires more drug to get the same therapeutic effect.


    http://forums.steroid.com/showthread...=346777&page=5

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    wow that thread is pretty nice. i just read like half a page of questions with no relevance to me at all.. the one about catatonic people was very interesting. off topic, but did you ever see the movie based on that with robin williams? i forget the name

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    MuscleScience is online now AR-Hall of Famer
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    Quote Originally Posted by T_Own View Post
    wow that thread is pretty nice. i just read like half a page of questions with no relevance to me at all.. the one about catatonic people was very interesting. off topic, but did you ever see the movie based on that with robin williams? i forget the name
    You talking about Patch Adams?

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    no, Awakenings

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    MuscleScience is online now AR-Hall of Famer
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    Quote Originally Posted by T_Own View Post
    no, Awakenings
    I may have, sounds familiar.

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    Quote Originally Posted by MuscleScience View Post
    This is a response to a question in my Q@A thread about drug tolerance:

    The body has a mechanism that can render drugs inactive. If you think about it anytime you put something in your body you disrupt its normal physiology. The body wants to be in its normal operating range. The Liver specifically expresses a family of enzymes commonly know as the cytochrome P450 oxidases (CYP). This group of enzymes is very diverse and has important functions.
    http://forums.steroid.com/newreply.p...eply&p=4325018
    Anabolic Steroids - Steroid .com / Anabolic Review Forums - Reply to Topic
    When the body is exposed to a compound lets call it compound X. The body reacts to it by up regulating the expression of CYP that is specific to that compound. CYP will react with compound X rendering it chemically inactive. Usually by oxidizing the compound which is known as Phase I metabolism by pharmacologist. This leads to drug tolerance which requires more drug to get the same therapeutic effect.


    http://forums.steroid.com/showthread...=346777&page=5
    Glad u posted this as it jarred memory re hormones and this system. Good info and true that about 60% of all drugs are actually removed from our body via this mechanism. Didnt think explaining this was helpful UNTIL remembering that it applies to hormones as well (pretty sure based on female birth control meds(ethynyl estradiol) being removed via this mechanism) Only approx 6 specific cyp enzymes are responsible from removing drugs from the human system and 75-80% of all drugs that are removed via this mechanism are removed by 2 very specific cyp enzymes (sure u know fam/subfam /gene classification system)..then onto detox phase(aka phase 2). In retrospect as I said I rembered hormones are in fact removed via this mechanism (im 90 % sure-jump in if im wrong) SO the million dollar question IS how long will the cyp enzyme remain present after cessation of introduction exogenous test (or other anabolics) causing downregulation in receptor responsiveness? With most drugs longer term use results in longer term downregulation in recptor responsiveness. Based on that ..id hypothesize (and do) that the longer the cycle the longer it would take for upregulation of recpetor responsiveness.

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    Quote Originally Posted by Mulciber View Post
    your not concerned about recovery of HPTA before jumping back on...
    have any bloodwork done?
    Did bloodwork and everything is 100% within normal range.

    I am finishing my PCT so that i recover before i start again. Why not just stay on and bridge? id personally like my balls to remember how to produce test. Atleast if they restart then i know im good to go again.

    I will also test that i have had full recovery of my HPTA before i ever started.

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    Quote Originally Posted by jimmyinkedup View Post
    *L* I love it ...wait till someone gives the answer you want to hear...latch on to that ...and ask that person for reassurance...... who needs bloodwork???? dude on board said its cool ...oh brother....
    you didnt even understand my question... why would i have listened to anything you said.

    he was the only other one who had posted in this thread.


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    Quote Originally Posted by MuscleScience View Post
    This is a response to a question in my Q@A thread about drug tolerance:

    The body has a mechanism that can render drugs inactive. If you think about it anytime you put something in your body you disrupt its normal physiology. The body wants to be in its normal operating range. The Liver specifically expresses a family of enzymes commonly know as the cytochrome P450 oxidases (CYP). This group of enzymes is very diverse and has important functions.

    When the body is exposed to a compound lets call it compound X. The body reacts to it by up regulating the expression of CYP that is specific to that compound. CYP will react with compound X rendering it chemically inactive. Usually by oxidizing the compound which is known as Phase I metabolism by pharmacologist. This leads to drug tolerance which requires more drug to get the same therapeutic effect.


    http://forums.steroid.com/showthread...=346777&page=5

    reading it now, thanks.

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    Mulciber is offline Scammer
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    ///////nevermind..

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    Quote Originally Posted by jimmyinkedup View Post
    Glad u posted this as it jarred memory re hormones and this system. Good info and true that about 60% of all drugs are actually removed from our body via this mechanism. Didnt think explaining this was helpful UNTIL remembering that it applies to hormones as well (pretty sure based on female birth control meds(ethynyl estradiol) being removed via this mechanism) Only approx 6 specific cyp enzymes are responsible from removing drugs from the human system and 75-80% of all drugs that are removed via this mechanism are removed by 2 very specific cyp enzymes (sure u know fam/subfam /gene classification system)..then onto detox phase(aka phase 2). In retrospect as I said I rembered hormones are in fact removed via this mechanism (im 90 % sure-jump in if im wrong) SO the million dollar question IS how long will the cyp enzyme remain present after cessation of introduction exogenous test (or other anabolics) causing downregulation in receptor responsiveness? With most drugs longer term use results in longer term downregulation in recptor responsiveness. Based on that ..id hypothesize (and do) that the longer the cycle the longer it would take for upregulation of recpetor responsiveness.
    I actually asked a toxicologist this question the other day, as far as how long CYP is expressed for a particular drug. I asked him if there was a residual memory say if you took a drug for however long and then stopped and did not retake it again for a long period of time. If CYP would be expressed or upregulated faster much like the immune system does for pathogens and antibody expression.

    He told me there was no residual memory and the length of time for CYP to be de-expressed in a cell was dependent on how much of the drug had been used and for how long. He explained in general it only takes a few weeks for CYP expression to return to normal after cessation of a drug regime such as typically prescribed by an MD for short term conditions.

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    It's actually been found that androgen receptors in muscle cells don't downregulate.

    In the presence of superphysiological amounts of androgens, cells actually grow and increase MORE receptors in muscle cells. So, even if there was downregulation going on, it wouldn't matter because more receptors are being created as more androgens are added.

    This is why many believe the decrease in gains in a cycle and subsequent cycles occurs is because of other factors such as SHBG increases, cortisol increases, genetic limitations being reached when more muscle is built, etc.

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    Quote Originally Posted by FirstTimeRage View Post
    Did bloodwork and everything is 100% within normal range.

    I am finishing my PCT so that i recover before i start again. Why not just stay on and bridge? id personally like my balls to remember how to produce test. Atleast if they restart then i know im good to go again.

    I will also test that i have had full recovery of my HPTA before i ever started.
    How did you get bloodwork done when your still in pct?? You should have bloodwork done 2 months after completion of pct to make sure your liptids and hpta has fully recovered.

    Disclaimer-BG is presenting fictitious opinions and does in no way encourage nor condone the use of any illegal substances.
    The information discussed is strictly for entertainment purposes only.


    Everything was impossible until somebody did it!

    I've got 99 problems......but my squat/dead ain't one !!

    It doesnt matter how good looking she is, some where, some one is tired of her shit.

    Light travels faster then sound. This is why some people appear bright until you hear them speak.

    Great place to start researching ! http://forums.steroid.com/anabolic-s...-database.html


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    Quote Originally Posted by Atomini View Post
    It's actually been found that androgen receptors in muscle cells don't downregulate.

    In the presence of superphysiological amounts of androgens, cells actually grow and increase MORE receptors in muscle cells. So, even if there was downregulation going on, it wouldn't matter because more receptors are being created as more androgens are added.

    This is why many believe the decrease in gains in a cycle and subsequent cycles occurs is because of other factors such as SHBG increases, cortisol increases, genetic limitations being reached when more muscle is built, etc.
    yes x2. If receptors didnt constantly regenerate guys like Cutler and Victor would not be able to maintain their size.

    Disclaimer-BG is presenting fictitious opinions and does in no way encourage nor condone the use of any illegal substances.
    The information discussed is strictly for entertainment purposes only.


    Everything was impossible until somebody did it!

    I've got 99 problems......but my squat/dead ain't one !!

    It doesnt matter how good looking she is, some where, some one is tired of her shit.

    Light travels faster then sound. This is why some people appear bright until you hear them speak.

    Great place to start researching ! http://forums.steroid.com/anabolic-s...-database.html


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    Quote Originally Posted by BG View Post
    How did you get bloodwork done when your still in pct?? You should have bloodwork done 2 months after completion of pct to make sure your liptids and hpta has fully recovered.
    I didnt check for hpta.

    i was checking everything else.

    when i am done my pct i will check hpta. i would not start another cycle untill i am fully recovered from the last one.

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    Quote Originally Posted by Atomini View Post
    It's actually been found that androgen receptors in muscle cells don't downregulate.

    In the presence of superphysiological amounts of androgens, cells actually grow and increase MORE receptors in muscle cells. So, even if there was downregulation going on, it wouldn't matter because more receptors are being created as more androgens are added.

    This is why many believe the decrease in gains in a cycle and subsequent cycles occurs is because of other factors such as SHBG increases, cortisol increases, genetic limitations being reached when more muscle is built, etc.
    Hmm ...again im no expert in the area of hormones per say but re pharmaceuticals or even other drugs ..take for example nicotine ...while # of receptors increase (not that uncommon) there is still an expressed downregulation. The new # of increassed receptors cannot offset downregulation of existing receptors. Downregulation def is for real and is proven to take place....if i had to hypothicize i would be hard pressed to believe the body mechanism behaves differently with hormones since the same mechanism (cyp enzyme) metabolizes both (albeit possibly diff cyp enzyme - possibly not - only about 6 total responsible for all drug metabolization in body) however it is the human body so who knows. This is an interesting topic and i bet theories abound both ways. I do however think that most people are prob best served waiting appropriate lengths between cycles ..but you know what people are gonna do what they wanna do anyway and then they will find out what best works (or doesnt for them). I think to say downregulation 100% doesnt exist with anabolics would require quite a bit of speculation as would saying it 100 % does exist. My personal opinion based on limited knowledge and my own speculation based on bodies reaction to other chemicals (medications/drugs) is it does ...but you know what they say about opinions!

    Oh and muscle science the info you posted above about the cyp enzyme presence time being dependant on amount of substance used and dosage maske alot of sense and ties in with real world example. Thanks!
    Last edited by jimmyinkedup; 12-07-2008 at 12:17 PM.

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    Quote Originally Posted by FirstTimeRage View Post
    you didnt even understand my question... why would i have listened to anything you said.

    he was the only other one who had posted in this thread.

    sorry ..i guess i just cant quite grasp what you meant ...gave alot of info i thought MIGHT be pertinent and helpful ...if not in your opinion cool . Sorry I couldnt help - best of luck. Oh btw no one can give u a 100% difinitive answer to your question. Its pretty obvious what u want to believe ..and thats cool ...best of luck.

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    Quote Originally Posted by MuscleScience View Post
    This is a response to a question in my Q@A thread about drug tolerance:

    The body has a mechanism that can render drugs inactive. If you think about it anytime you put something in your body you disrupt its normal physiology. The body wants to be in its normal operating range. The Liver specifically expresses a family of enzymes commonly know as the cytochrome P450 oxidases (CYP). This group of enzymes is very diverse and has important functions.

    When the body is exposed to a compound lets call it compound X. The body reacts to it by up regulating the expression of CYP that is specific to that compound. CYP will react with compound X rendering it chemically inactive. Usually by oxidizing the compound which is known as Phase I metabolism by pharmacologist. This leads to drug tolerance which requires more drug to get the same therapeutic effect.


    http://forums.steroid.com/showthread...=346777&page=5
    Ok, about two weeks, now my question is another.

    After how much time did the CYP oxidize the hormone at such a high percentage that it's no more effective or after how much time the CYP activity may became liver toxic ?

    I'm obviously referring to bridging and cruising procedures.

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    Androgen Receptors Downregulate - Don't They? Part 1
    By Bryan Haycock MS

    Please send us your feedback on this article.

    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.

    Androgen Receptors Downregulate - Don't They? Part 2
    By Bryan Haycock MS

    Please send us your feedback on this article.

    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.

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    Quote Originally Posted by sergioitalian View Post
    Ok, about two weeks, now my question is another.

    After how much time did the CYP oxidize the hormone at such a high percentage that it's no more effective or after how much time the CYP activity may became liver toxic ?

    I'm obviously referring to bridging and cruising procedures.
    Thats a good question and to tell you the truth I do not know. I browsed about 250 papers and never once found any time frame of up regulation in humans. The only thing I could find that may have any relevance is that CYP activity and testosterone is tissue specific. Meaning that the liver, heart and muscles will all metabolize testosterone differently, which is probably no surprise.

    I did find a few papers in animal models that showed CYP activity increase in two weeks in hamsters, which are often used in cancer studies.

    http://carcin.oxfordjournals.org/cgi...etype=HWCIT#T2

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    so 2 weeks, got a nice solid answer right there, where did you get this info from so i can go check it out?

    now the next question is the same as you stated above regarding CYP activity... soooooo BUMPPP

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    Quote Originally Posted by FirstTimeRage View Post
    so 2 weeks, got a nice solid answer right there, where did you get this info from so i can go check it out?

    now the next question is the same as you stated above regarding CYP activity... soooooo BUMPPP
    I referenced one of the papers I talked about.

    I did a lit search on highwire.org, it has a lot of free journals for those that dont have full journal rights like I do at school.

    My search keywords were cytochrome p450 testosterone just as it appears. There was over 3900 papers just with those key words.

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    Here is a thread a couple of threads with similar questions.

    http://forums.steroid.com/showthread.php?t=365103

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    atomini and muscle science..not my thread but great info /reads / and opinions. Good Stuff. I already expressed my opinion re downregulation but I can def see both sides...my biggest question is if the above theory re new recptor sites created (which i agree they prob are) is #1 does it happen a rate that offsets downreg (or if u dont buy the doenreg theory at all - at a rate that keeps compound equally as effective ) OR #2 How long does it take for new recptor sites to be created - for example it happens with nicotine but takes months and months and months of continuous use(most aas users do cycles, not year round high dose administration-year after year). I see haycocks theory on why anabolic hormones are diff but there is an equal amount of specualiton in his theory as well. You can substantiate either theory with an abundance of scientific studies. At any rate great info and great thread....in spite of my not understanding the original question *L*
    obviously the other consideration pointed out early in thread is the effect on hpta and how not waiting could adveresly effect return of functionality.
    Last edited by jimmyinkedup; 12-09-2008 at 04:15 PM.

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    He told me there was no residual memory and the length of time for CYP to be de-expressed in a cell was dependent on how much of the drug had been used and for how long. He explained in general it only takes a few weeks for CYP expression to return to normal after cessation of a drug regime such as typically prescribed by an MD for short term conditions.

    How do you guys get 2 weeks from this? do you consider steroid cycle comparable in time /dosage to a typical drug regime prescribed by md for short term condition??? Far from the same. Id pay much more heed to italicized info ...even though it isnt what you want to hear....
    Last edited by jimmyinkedup; 12-09-2008 at 07:16 PM.

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    Quote Originally Posted by jimmyinkedup View Post
    He told me there was no residual memory and the length of time for CYP to be de-expressed in a cell was dependent on how much of the drug had been used and for how long. He explained in general it only takes a few weeks for CYP expression to return to normal after cessation of a drug regime such as typically prescribed by an MD for short term conditions.

    How do you guys get 2 weeks from this? do you consider steroid cycle comparable in time /dosage to a typical drug regime prescribed by md for short term condition??? Far from the same. Id pay much more heed to italicized info ...even though it isnt what you want to hear....
    I wasnt talking about steroids , i was meaning that the typical prescription period he mentioned to me was a week or two, For most pain killers and anti-biotics.

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    ^^^^ no, no i understand what u said and meant however i think at least 2 posts by 2 diff people after yours applied this info to aas (when clearly increased dosage and increased duration alone with make the comparision not very sound IMO). I knew exactly what u meant and appreciated you going out of your way to ask someone who would know and provide the info you did. Hope that clarifies...seamus
    Last edited by jimmyinkedup; 12-09-2008 at 07:24 PM.

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    Quote Originally Posted by jimmyinkedup View Post
    ^^^^ no, no i understand what u said and meant however i think at least 2 posts by 2 diff people after yours applied this info to aas (when clearly increased dosage and increased duration alone with make the comparision not very sound IMO). I knew exactly what u meant and appreciated you going out of your way to ask someone who would know and provide the info you did. Hope that clarifies...seamus
    Ok.....LOL,

    just making sure....

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    This is good reading. I hope this thread stays open and more people chime in. Maybe it should be made a sticky in the educational threads. I do agree with the process of down regulation with regards to prescription meds and other substances. I think the kicker question is how and if down regulation occurs with regards to a natural occuring hormone such as testosterone when it introduced supplementally for extended periods of time off and on? Thanks Automini for providing the informative post.

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    Quote Originally Posted by Gym Freak View Post
    This is good reading. I hope this thread stays open and more people chime in. Maybe it should be made a sticky in the educational threads. I do agree with the process of down regulation with regards to prescription meds and other substances. I think the kicker question is how and if down regulation occurs with regards to a natural occuring hormone such as testosterone when it introduced supplementally for extended periods of time off and on? Thanks Automini for providing the informative post.
    It does, but not by receptor down regulation. There is a concept called negative feedback inhibition (aka: negative feedback loop) in regards to hormone regulation in the body. For example when testosterone is high in the body. The pituitary gland (anterior pituitary) senses this and decreases the secretion of Luteinizing hormone, which acts on the Leydig cell of the testis to produce testosterone. The process works in reverse when testosterone is low.

    Keep in mind this is a very simplistic example and there are of course other process the affect circulating testosterone. In general this is a good way to describe how the body self regulates itself.

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    Quote Originally Posted by MuscleScience View Post
    It does, but not by receptor down regulation. There is a concept called negative feedback inhibition (aka: negative feedback loop) in regards to hormone regulation in the body. For example when testosterone is high in the body. The pituitary gland (anterior pituitary) senses this and decreases the secretion of Luteinizing hormone, which acts on the Leydig cell of the testis to produce testosterone. The process works in reverse when testosterone is low.

    Keep in mind this is a very simplistic example and there are of course other process the affect circulating testosterone. In general this is a good way to describe how the body self regulates itself.
    But this process will happen whether your injecting a small or large amount of supplemental test. You can run your test at 100mg a week or 1000mg a week and the process of this negative feedback loop will take place. You can also run a cycle for 2 weeks or 12 weeks and the process will still be the same. As you said prior, if you are introducing supplemental test. your leydig cells will stop producing testosterone no matter the cycle length or dose of testosterone. Please correct me if I am wrong. That's why we run PCT so as to stimulate those leydig cells. I know this is simplified but isn't that the just of it.

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