AR downregulation myth- with scientific studies
- 01-20-2011, 08:31 PM
AR downregulation myth- with scientific studies
There is much talk on the net about roids some people know what they are talking about, and some well are just reinforcing myths. One thing I hear about all the time is the topic of androgen receptors or (ARs). It seems many people still believe that over the course of a cycle ARs downgrade this just isnt the case. People argue the downgrade point because of the fact there comes a time growth slows or stops though the dose of testosterone hasn't changed.
It also stems from the fact that we know other receptors of the body do downgrade. Take ephedrine for example, it binds to beta-receptors, over a period of time the number of receptors on a target cell 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 which leads to a decrease in the potency of a given dose.
The above happens with many substances and receptors but androgen receptors are very different. Many studies that are coming out these days show in the presence of high concentrations of testosterone receptors up regulate to consume the higher amounts of testosterone in the body. When you stop growing it is not because of down regulation and here is why.
Most everyone knows a little about how steroids work increased protein synthesis right? Well there is much more to it than that. They also increase the activity of satellite cells, GH and igf-1, also increase new myofiber formation.
In one study I read a 500mg injection of testosterone per week increased GH levels by 18% and IGF-1 levels by 15% that shows a powerful effect! Activation of satellite cells by testosterone requires IGF-1 and as a loop effect aromatized test that turns to estrogen again increases IGF-1 so each plays off the other with the end result being increased satellite cell production. This leads to a greater capacity for protein synthesis by increasing fusion of satellite cells to existing fibers.
Proliferation of satellite cells is needed 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.
So you see the increased test levels actually increase satellite cells which in turn down the road increase receptors. It also seems the higher the dose the more the activity of satellite cells increase. That doesn't mean jump right in to 2-3g doses of test you have to build up receptors over time. All jumping up to a huge amount of test will do is give you an estrogen level of a tranny queen who happens to have muscle lol.
Here are a few quotes to support my claims
Endocrinology (1990) 126 1165. In fibroblasts cultured from human genital skin which contained very low amounts of 5-alpha reductase, 2 nanomolar tritium-labeled testosterone [which is sufficient to saturate ARs] produced a 34% increase in androgen receptors as measured by specific AR binding, the best assay method known, and 20 nanomolar tritium-labeled testosterone produced an increase of 64% in number of ARs.
J Steroid Biochemistry and Molecular Biology (1990) 37 553. In cultured adipocytes, methyltrienolone and testosterone demonstrated marked up regulation of AR content upon administration of androgen. 10 nanomolar methyltrienolone increased AR content (as measured by binding to radiolabeled androgen) by more than five times, relative to zero androgen.
J Steroid Biochemistry and Molecular Biology (1993) 45 333. In cultured smooth muscle cells from the penis of the rat, mRNA production was found to be up regulated by high dose testosterone (100 nanomolar) or DHT. When 5-alpha reducatase was inhibited by finasteride, thus blocking metabolism to DHT, AR mRNA production was down regulated in response to testosterone. Blockage of the aromatization pathway to estrogen by fadrozole eliminated this downregulation effect. Estradiol itself was found to down regulate AR mRNA production in these cells.
Endocrinol Japan (1992) 39 235. One nanomolar DHT was demonstrated to increase AR protein by over 100% within 24 hours, relative to zero androgen level. The half life of the AR was demonstrated to increase from 3.3 h to 7.5 h as a result of the androgen administration.
Endocrinology (1996) 137 1385. 100 nanomolar testosterone was found to increase AR levels in vitro in muscle satellite cells, myotubes, and muscle-derived fibroblasts.
The main reason growth stops when the dose remains the same is the body doesn't like change, it will fight you every step of the way. When you increase the amount of anabolic hormones, catabolic hormones will rise as well. When the concentration of catabolic hormones is high enough growth is off set or even stops. When that happens you can do one of two things. Stop taking gear so the body can return to normal or increase the amount of test to once more be in an anabolic state. The increase in receptors is the reason you can use more and more test every cycle, and the funny thing is these receptors once built will hang around for a very long time even years ever increasing your ability to build muscleTest e/dbol/epi/winnie
- 01-21-2011, 02:34 PM
Bump this **** is important to crush the mythsTest e/dbol/epi/winnie
- 01-21-2011, 03:16 PM
hmmm, impressive schwell, you've come a long way bro.
so are you trying to say I dont know what im talking about and reinforce myths!
01-21-2011, 03:35 PM
Man, you just need to step away from the keyboard. You are seriously going to plagiarize priests work and claim it your own?
Please explain to me your quotes that support your claims. Considering the very article that priest hijacked from is contradictory in that it mentions the science isn't solid since all the research is done on cultured cells relieving the cells of having any type of natural homeostasis. Cultured cells are free of floating test, estrogen, cortisol, so essentially there is no such thing as supra physiological levels to cultured cells. Just a FYI, Priests work is direct pull from Bill Roberts work.
You could very well be right... but have the know how on how to present a compelling case instead of copying and pasting a flawed article.
you copied and pasted that whole thing attempting to claim it as your own work.
The Historic PES Legend
01-21-2011, 04:43 PM
I never said it was my own- no where NO WHERE did i say it was my own
lol cmon now i DID NOT write this
01-21-2011, 04:44 PM
01-21-2011, 05:01 PM
Plagiarism is one of my biggest pet peeves, especially on a forum that you share idea's and discuss theory. It is dishonest and discredits the perpetrators past and future information.
The Historic PES Legend
01-21-2011, 05:17 PM
01-21-2011, 05:47 PM
well, we know that schwell, just remember to cite your source if your not speaking from memory.
no need to go all eng 101 on it like your publising a book, just be like "source: anabolics 09" for example.
no harm no foul, your still a little new.
but come to know, if your going to talk about theroies such as this, you're going to have to be prepared for critics, and the only logical way is to quote your sources as your info.
and it's always important to read the studies if you can, that your source quotes.
01-21-2011, 07:36 PM
good point jbryand- i read the article and found it very interesting- i do need to read the studies cited before i denounce AR downregulation though you are correct
01-21-2011, 09:29 PM
01-21-2011, 09:51 PM
the point is people being able to read the studies for themselves and come up with their own conclusion.
this article is just one persons opinion on the subject matter.
if you just believe everything people say that sounds good, I've got some magic beans that will make you gain 20lbs of lean muscle....
01-21-2011, 09:53 PM
01-21-2011, 09:54 PM
01-21-2011, 09:56 PM
01-21-2011, 09:57 PM
01-21-2011, 10:10 PM
The original information was contested by Bill Roberts who provided the original information and studies but also said the information was flawed and presented studies that showed AR down regulation.
The proliferating studies were all done on cultured muscle and fat cells (Grown in a lab), so a real observation can't exactly be drawn.
The Historic PES Legend
01-21-2011, 10:28 PM
schwell should be the vollunteer to inject 600mg of test, lift, then allow multiple muscle bi-opsies & tissue samples from various parts of the body, then we'd be getting somewhere.
01-21-2011, 10:31 PM
01-21-2011, 11:24 PM
i will do so, yuhz send it to dadams and jbryand for analysis
01-22-2011, 12:36 AM
01-22-2011, 07:02 AM
I have stated before that there really isn't definitive proof either way and that I lean towards downregulation - the fact that stem cells need AR is true however the absolute number of AR is irrelevent but rather the number of AR per DNA unit is what is really important since AR must bind to response sites on DNA to elicit an effect and AR/DNA is therefore a functional unit. Simply showing increased number of receptors, especially in a situation of myonucleation doesn't mean anything other than the fact that hypertrophy/hyperplasia is occuring. It is accepted that increased receptor density (when expressed as receptor quantiy per DNA) dicates the responsiveness of a tissue or organ system to androgen. For example, the prostate has many fold higher density of androgen receptor compared to skeletal muscle and is therefore more androgen responsive. Therefore, if you increase the density you are making a tissue more responsive. In the context of an AAS cycle, does skeletal muscle get more or less responsive to the drugs being utilized?
In any case, I have also said that it really doesn't matter. What is important is that desensitization occurs - whether it be through downregulation of AR, upregulation of GR, increase in cortisol, or some other mechanism. I always find it funny how strongly people will argue about uprgeulation but usualy I find the reason that they do so is because somehow in their minds it justifies the use of higher doses of AAS.
01-22-2011, 06:16 PM
01-22-2011, 07:09 PM
i really like high doses of aas yes sir i do
01-22-2011, 11:27 PM
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