AAS tolerance

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  1. AAS tolerance


    So given that one needs increasing dosages of AAS to create the same effects as time passes, this must mean that the body is devloping tolerance to it.

    I do have a few questions regarding that

    1) how does this tolerance work? Is it the body's tolerance to the AAS itself, or simply because after a cycle, the body attins more muscle and hencem it is harder to gain more muscle WITH more mucle?

    2) if one stops AAS usage for an extended period of time (say a year), KEEPS the msucle, and then begins anotehr cycle, would teh second cycle be as good as teh first?

    3) if one stops AAS usage for an extended period of time (say a year), LOSES the msucle, and then begins anotehr cycle, would the second cycle be as good as the first?

    4) if one's body devlopes tolerance, then wouldnt people who are on long term TRT feel the effects of their TRT decline over time?


  2. a lot of variables here.

    genetic limit is one. once u pass ur genetic limit u basically have to stay on AAS to stay that size. gains, even on AAS, are hard to produce once passed ones limit. this is when most incorporate HGH.

    many have done cycles of test only at moderate doses and still see great gains 10 cycles later at the same dose. this is mainly diet and goal dependent.

    as long as u take an adequate break after PCT to allow ur body to recover etc. then gains on ur next cycle should be just as good as ur first.
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  3. Whao ok hold on thats a lot of good stuff there.

    The thing is, I am on TRT for good now, but only at 200mg/week. Durnig my 'on cycle' I want to stack it with 150mg more TNE per week.

    When I go off cycle, and continue with the 200mg/wk TRT, would that be not giving my body a break or?

    What I propose to do is this: cycle of 8-12 weeks. Off (still on TRT) for 4-6 weeks, then on again. Repeat until I believe my genetic potential is reached (I have trained for 7 years already, but not much progress due to low testsoterone that required me to seek TRT). WHen I say genetic poetntial, I mean stagnant gains no matter how smart or hard I train.

    Does that sound 'ok'?

  4. have u every heard of "blasting" and "cruising"? what u want to do is basically that. except that u will NEVER need to run a PCT, which personally i think is nice.

    what u have planned looks fine. what is TNE though?

  5. Quote Originally Posted by nosnmiveins View Post
    over-saturation of receptors is the main culprit for slowed/stopped gains on cycle.
    What do you mean "over-saturation of receptors"? If all the receptors are bound to a ligand, that would produce an effect, not explain the lack of an effect.

    Do you mean that the main culprit is down-regulation of the androgen receptor? Because that's also not the case. Unlike clen and the adrenoreceptor, steroids actually up-reguate the androgen receptor.
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  6. Blasting and cruising. O I like the sound of that. Cruise is to give teh body a break while preserving gained mass right?

    Sweet.

    TNE = testosterone no ester (test base, test suspension).

    Yes receptor down regulation makes no sense also because if they are downregulated, then no matter how much yo increasse dosages, it shoudl not work, as theer are less recptors. Once a receptor is bound, it is bound, adding mroe will not make it bind 'more'.

    I think it could possibly be beucase when you run cycle after cycle, you are taxing your msuckes. I think maybe it is the musckles themelsves that need a break, AAS or no AAS. Ofcourse,m thats just an airy assumption..

  7. i blast and cruise, it works but the constant pinning gets pretty annoying, and if i have to travel its a task to bring an amp or often much more with me. only had this problem one time, where i had to miss a pin for over a week due to a vacation which ended in me losing my sex drive at a very important time :P

  8. i think you must consider that the first time you do a cycle, you probably was less strong, smaller; so when you begin at 180 lb you put 15 lb (for example) but when you stay at 200 is more difficoult to put another 15. the same without Roids, in the first years with a normal diet and normal training you get result, than you must train more or eat better to improve. because you're reaching the limit.

    the example you posted (like a man lose his muscle or not, in a couple of years, can't explain a lot, because even the other variable are changed, like receptor for example).

    for what I know, the androgen receptor don't downregulate for the presence of Androgens, but probably bigger muscle need more androgen (if 10kg of muscle need 100 ng/l testo to survive, probably 50 kg muscle need 500ng/l testo)

  9. Quote Originally Posted by Conciliator View Post
    What do you mean "over-saturation of receptors"? If all the receptors are bound to a ligand, that would produce an effect, not explain the lack of an effect.

    Do you mean that the main culprit is down-regulation of the androgen receptor? Because that's also not the case. Unlike clen and the adrenoreceptor, steroids actually up-reguate the androgen receptor.

    good point, my mistake. dunno what i was thinking at the time, reps

  10. "test susp (base) should be shot ED..."

    Does this also apply if I am stacking it with test E shot twice weekly?

  11. Quote Originally Posted by rombusempire View Post
    "test susp (base) should be shot ED..."

    Does this also apply if I am stacking it with test E shot twice weekly?

    yes because test base has no ester attached to it, so it basically kicks in immediately. most people will pin twice a day, but im sure once is good

  12. So if I ran phera at 45/60/60/45 right now, will I still be able to make gains on a later cycle with phera lets say at 15/30/30/45?

  13. Quote Originally Posted by rombusempire View Post
    Blasting and cruising. O I like the sound of that. Cruise is to give teh body a break while preserving gained mass right?

    Sweet.

    TNE = testosterone no ester (test base, test suspension).

    Yes receptor down regulation makes no sense also because if they are downregulated, then no matter how much yo increasse dosages, it shoudl not work, as theer are less recptors. Once a receptor is bound, it is bound, adding mroe will not make it bind 'more'.

    I think it could possibly be beucase when you run cycle after cycle, you are taxing your msuckes. I think maybe it is the musckles themelsves that need a break, AAS or no AAS. Ofcourse,m thats just an airy assumption..
    Conciliator and I disagree on this one and I am sure he will rush in to debate me but here is the deal:

    A molecule of steroid binds to a receptor. Two receptors bind together to form a homodimer which then binds a "receptor" on DNA called a hormone response element. These response elements can either increase or decrease the expression of the genes that they regulate. So, for every nucleus (muscle cells are multinucleated) you have the genome of DNA and the "receptors" (HRE's) for the steroid-receptor complex. As you increase muscle size, you also increase the number of myonuclei and therefore, the body increases the number of androgen receptors to ensure that there is adequate stimulation per unit of DNA (so for example, you increase one unit of DNA and one unit of receptor but there is still a 1:1 ratio). This is the "upregulation" that a lot of papers mention. There is also another form of upregulation where the number of receptors per unit DNA is increased - this is true upregulation and occurs in the absence of androgen (for instance, castrated animals, women, and chemically castrated men). It is the bodies response to try to increase the likelihood of androgen receptor activation and The corollary also occurs, that is, the number of androgen receptors per unit DNA is decreased -- this occurs in response to androgenic stimulation. So, in the end, you could get an increase in the number of receptors but still have a net downregulation due to the ratio of androgen receptors to unit DNA actually being lower.

  14. Quote Originally Posted by sethroberts View Post
    A molecule of steroid binds to a receptor. Two receptors bind together to form a homodimer which then binds a "receptor" on DNA called a hormone response element. These response elements can either increase or decrease the expression of the genes that they regulate. So, for every nucleus (muscle cells are multinucleated) you have the genome of DNA and the "receptors" (HRE's) for the steroid-receptor complex. As you increase muscle size, you also increase the number of myonuclei and therefore, the body increases the number of androgen receptors to ensure that there is adequate stimulation per unit of DNA (so for example, you increase one unit of DNA and one unit of receptor but there is still a 1:1 ratio). This is the "upregulation" that a lot of papers mention. There is also another form of upregulation where the number of receptors per unit DNA is increased - this is true upregulation and occurs in the absence of androgen (for instance, castrated animals, women, and chemically castrated men). It is the bodies response to try to increase the likelihood of androgen receptor activation and The corollary also occurs, that is, the number of androgen receptors per unit DNA is decreased -- this occurs in response to androgenic stimulation. So, in the end, you could get an increase in the number of receptors but still have a net downregulation due to the ratio of androgen receptors to unit DNA actually being lower.
    I think you raise some interesting issues, but get into semantics when you argue what "true" upregulation is. The total number of androgen receptors is increasing. With the addition of myonuclei, there might not be an increase of AR per unit DNA, but there would be an increase of AR per muscle fiber.

    I'd argue that what matters is the total number of androgen binding sites. Androgens increase the number of myonuclei in muscle fibers, which in turn increase the total number of androgen binding sites. This makes muscle more susceptible to androgens.

    Keep in mind that an increase in myonuclei is not the only mechanism of action for AR upregulation. There's research showing that androgens also increase the half life of the androgen receptor. So not only is there an increase in de novo receptor synthesis, but existing receptors are stabilized.

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  16. Quote Originally Posted by Conciliator View Post
    I think you raise some interesting issues, but get into semantics when you argue what "true" upregulation is. The total number of androgen receptors is increasing. With the addition of myonuclei, there might not be an increase of AR per unit DNA, but there would be an increase of AR per muscle fiber.

    I'd argue that what matters is the total number of androgen binding sites. Androgens increase the number of myonuclei in muscle fibers, which in turn increase the total number of androgen binding sites. This makes muscle more susceptible to androgens.

    Keep in mind that an increase in myonuclei is not the only mechanism of action for AR upregulation. There's research showing that androgens also increase the half life of the androgen receptor. So not only is there an increase in de novo receptor synthesis, but existing receptors are stabilized.
    In the end, what it comes down to for me is that androgen receptor antagonists and castration seem to result in greater sensitivity of the system (i.e. upregulation) while stimulation results in decreased sensitivity which is a basic tenant of receptor physiology as stated in several standard texts on the subject.

  17. A molecule of steroid binds to a receptor. Two receptors bind together to form a homodimer which then binds a "receptor" on DNA called a hormone response element. These response elements can either increase or decrease the expression of the genes that they regulate. So, for every nucleus (muscle cells are multinucleated) you have the genome of DNA and the "receptors" (HRE's) for the steroid-receptor complex. As you increase muscle size, you also increase the number of myonuclei and therefore, the body increases the number of androgen receptors to ensure that there is adequate stimulation per unit of DNA (so for example, you increase one unit of DNA and one unit of receptor but there is still a 1:1 ratio). This is the "upregulation" that a lot of papers mention. There is also another form of upregulation where the number of receptors per unit DNA is increased - this is true upregulation and occurs in the absence of androgen (for instance, castrated animals, women, and chemically castrated men). It is the bodies response to try to increase the likelihood of androgen receptor activation and The corollary also occurs, that is, the number of androgen receptors per unit DNA is decreased -- this occurs in response to androgenic stimulation. So, in the end, you could get an increase in the number of receptors but still have a net downregulation due to the ratio of androgen receptors to unit DNA actually being lower.
    Reps.

    With the addition of myonuclei, there might not be an increase of AR per unit DNA, but there would be an increase of AR per muscle fiber.
    If new nuclei are made and fuse with existing cells while those cells are down regulating the androgen receptor, wouldn't you just be breaking even in terms of net androgen receptor availability?

  18. Quote Originally Posted by LSU Gladiator View Post
    If new nuclei are made and fuse with existing cells while those cells are down regulating the androgen receptor, wouldn't you just be breaking even in terms of net androgen receptor availability?
    What do you mean that "those cells are down regulating the androgen receptor"? The half life of the receptor is increased and you're synthesizing new receptors. You're not "just breaking even". There's a net increase in androgen receptor binding sites. As several studies state, that leads to an increase in susceptibility to androgens.

    There are plenty of other possible explanations for the apparent functional loss seen with extended steroid use. Receptor down-regulation is simply not one of them.

  19. Quote Originally Posted by Conciliator View Post
    What do you mean that "those cells are down regulating the androgen receptor"? The half life of the receptor is increased and you're synthesizing new receptors. You're not "just breaking even". There's a net increase in androgen receptor binding sites. As several studies state, that leads to an increase in susceptibility to androgens.

    There are plenty of other possible explanations for the apparent functional loss seen with extended steroid use. Receptor down-regulation is simply not one of them.
    In general what are you referring to here? Insulin sensitivity (I was thinking this was more diet related)?
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  20. Quote Originally Posted by sethroberts View Post
    In the end, what it comes down to for me is that androgen receptor antagonists and castration seem to result in greater sensitivity of the system (i.e. upregulation) while stimulation results in decreased sensitivity which is a basic tenant of receptor physiology as stated in several standard texts on the subject.
    Sounds like you're conflating functional downregulation with receptor downregulation. Just because there's decreased functionality does not entail that the androgen receptor has not upregulated (i.e. increased in density). The research clearly shows in vitro and in vivo that androgens upregulate the androgen receptor in humans.

    If you want to talk about the apparent reduction in general androgen effectiveness, there's definitely more to it than reduced androgen functionality. You need to address antecedant issues that affect androgen availability, such as metabolization by aromatase and 5-alpha-reductase, binding to SHBG, etc.

  21. Quote Originally Posted by Royd The Noyd View Post
    In general what are you referring to here? Insulin sensitivity (I was thinking this was more diet related)?
    No, I was referring to homeostatic changes in androgen availability due to metbolization or binding. There's probably also posttranslational regulation.

  22. Quote Originally Posted by rombusempire View Post
    So given that one needs increasing dosages of AAS to create the same effects as time passes, this must mean that the body is devloping tolerance to it.

    I do have a few questions regarding that

    1) how does this tolerance work? Is it the body's tolerance to the AAS itself, or simply because after a cycle, the body attins more muscle and hencem it is harder to gain more muscle WITH more mucle?

    2) if one stops AAS usage for an extended period of time (say a year), KEEPS the msucle, and then begins anotehr cycle, would teh second cycle be as good as teh first?

    3) if one stops AAS usage for an extended period of time (say a year), LOSES the msucle, and then begins anotehr cycle, would the second cycle be as good as the first?

    4) if one's body devlopes tolerance, then wouldnt people who are on long term TRT feel the effects of their TRT decline over time?
    My experience has been, long periods in between cycles (6-12 months), and I respond very well. However, I have only done 4 cycles in the past 5 year, so in this sense I am somewhat unexperienced.

  23. Quote Originally Posted by Gixxer82 View Post
    test susp (base) should be shot ED...
    I agree, that is a strange protocol for HRT. It seems like you would have some major peaks and valleys with that dosing. Depending on your weight, you should be on something like 100mg of test cyp/week. I know some guys who stop their TRT during the cycle, and build up a small cache Test from the TRT that they should have been using during that time, and cruise at a higher dose for a while to preserve gains.

  24. Quote Originally Posted by Conciliator View Post
    Sounds like you're conflating functional downregulation with receptor downregulation. Just because there's decreased functionality does not entail that the androgen receptor has not upregulated (i.e. increased in density). The research clearly shows in vitro and in vivo that androgens upregulate the androgen receptor in humans.

    If you want to talk about the apparent reduction in general androgen effectiveness, there's definitely more to it than reduced androgen functionality. You need to address antecedant issues that affect androgen availability, such as metabolization by aromatase and 5-alpha-reductase, binding to SHBG, etc.
    All of those things do play a role along with a few others. The literature is not quite as one sided as you make it seem. There is one paper in particular that I know you like to reference as support for upregulation (Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment). I have torn it apart in the past and in reality it supports exactly what I am saying, that androgen activation of pluripotent satellite cells results in terminal differentiation to a muscle cell and incorpation into existing myofibers. With this comes an increase in receptor number in this cell - their evidence for this is even somewhat spurious(in one measure, they are looking at the percentage of myonuclei that stain positive for AR -- of course you are going to get a greater number of nuclear androgen receptor with androgen therapy since nuclear enrichment is a direct result of androgen receptor acrtivation). In fact they show no significant increase in androgen receptor quantity in muscle fiber cytoplasm which is where you would expect to see enrichment of new androgen receptors since that is were they are expressed in their pre-bound state.

    In their cellular assays they are using GAPDH as a single housekeeping gene. It is well know that you must use more than one housekeeping gene (usually people use three), particularly with nuclear hormones because they can activate many of these so-called housekeeping genes and change their expression. Even using this flawed method in a culture of almost pure staellite cells, they only saw a smal lincrease in AR quantity that was only significant at the 0.05 level and only with DHT, not testosterone.

    The sad part is, a lot of papers say upregulation when they are really speaking about nuclear enrichment. The way that you state that upregulation is accepted fact smacks of bro-lore. There is some contention surrounding this topic among some of the best minds in nuclear hormone physiology (even though the experts that write textbooks agree with downreguation) but the bros on the boards have it all figured out. Just because you have a calculator does not make you a mathematician.

  25. Oh. nono

    The test base is not part of the HRT, only the 200mg/wk of test E is.

    The test base is soemthing I added in personally as I figured the HRT dosage is not enough for a true cycle.

    As for peaks and valleys, it is actually ok so far because I shoot test E twice a week (once per week indeed does suck towards then end of the week)

    The test base I use as a 'booster' b4 work outs.

    So no one here thinks that that is a good idea?

    Quote Originally Posted by LilPsychotic View Post
    I agree, that is a strange protocol for HRT. It seems like you would have some major peaks and valleys with that dosing. Depending on your weight, you should be on something like 100mg of test cyp/week. I know some guys who stop their TRT during the cycle, and build up a small cache Test from the TRT that they should have been using during that time, and cruise at a higher dose for a while to preserve gains.
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