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goku_kakarot77
New member
^^^^^^
is receptor downregulation a myth?
- Thread starter goku_kakarot77
- Start date
goku_kakarot77 said:
borrowed from another --
The myth of Receptor Downgrade
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 muscle .
nzrodney
Banned
Good read Eddy. I think that there is more & more info coming out to support that AR's dont downgrade in the presence of increased testosterone availability. Of course this does then raise the question of why is it necessary to cycle on & off AAS usage? Shoot me down & then ban me!!
Powerbuilder333
Timeout? No, timeouts are for Plats
I've always believed in ramping up my dosages to continue making gains until contest day.
Increasing satellite cells which increases receptors could be why my system has always worked in the past.
That being said, I do believe receptors do down regulate. Post contest I go cold turkey for several months (or years), then when I've jumped back on I experience tremendous immediate results. Possibly because the old receptors have been refreshed, and the addition of the new receptors allows a great deal of the AAS to work it's magic?
Pure speculation on my part, but I do get results...
Increasing satellite cells which increases receptors could be why my system has always worked in the past.
That being said, I do believe receptors do down regulate. Post contest I go cold turkey for several months (or years), then when I've jumped back on I experience tremendous immediate results. Possibly because the old receptors have been refreshed, and the addition of the new receptors allows a great deal of the AAS to work it's magic?
Pure speculation on my part, but I do get results...
goku_kakarot77
New member
bump
Dissect it any way you want, the body has limitations. It may have nothing at all to do with down-regulation. After all, I've been on 100 mgs of T a week and my T is still around 800, which is what it was 5 years ago. But there's a finite ability for muscle fibers to expand. Think of it like plant food. It makes plants grow bigger and faster, but if it's in a pot, they'll come a time when it just won't grow any bigger no matter how much food you give it.
nzrodney said:
Rod I'd ban you but you would probably fly to Colorado and kick my ass.
My first thought (off the cuff) is that the sides of uninterrupted use at cycle dosages would be a problem (secondary polycythemia would be a virtual guaranteed and the only to fix it would be 120 days of no exogenous androgens).
There would also be the prostate issue—may be hard to pee when it becomes the size of a cantaloupe.
Also, the soft tissue needs time to catch up to the increase in muscle strength.
The latest research links chronically high blood pressure and high (and ldl/hdl ratio) cholesterol to Alzheimer’s.
The enlargement and thickening of left ventricular wall is still a point of argument among the docs and some studies link it to dose while others link it to cycle duration ---but I think the evidence is pretty conclusive .
There some evidence that the immune system is compromised and is correlated directly to the length of the cycle (but I notice that at 41 I can’t do a 16 week heavy cycle anymore—so maybe the immune system is compromised by just the intensity of workouts x length—but what the hell do I know)
Finally, gear decrease glucose tolerance and increases insulin resistance that can be very close the physiologic symptoms of Type II diabetes that can be reversed within months of ending the cycle.
but then again i am not a doc who is on more than i am off so what the hell do i know
goku_kakarot77
New member
eddymerckx said:Rod I'd ban you but you would probably fly to Colorado and kick my ass.
My first thought (off the cuff) is that the sides of uninterrupted use at cycle dosages would be a problem (secondary polycythemia would be a virtual guaranteed and the only to fix it would be 120 days of no exogenous androgens).
There would also be the prostate issue—may be hard to pee when it becomes the size of a cantaloupe.
Also, the soft tissue needs time to catch up to the increase in muscle strength.
The latest research links chronically high blood pressure and high (and ldl/hdl ratio) cholesterol to Alzheimer’s.
The enlargement and thickening of left ventricular wall is still a point of argument among the docs and some studies link it to dose while others link it to cycle duration ---but I think the evidence is pretty conclusive .
There some evidence that the immune system is compromised and is correlated directly to the length of the cycle (but I notice that at 41 I can’t do a 16 week heavy cycle anymore—so maybe the immune system is compromised by just the intensity of workouts x length—but what the hell do I know)
Finally, gear decrease glucose tolerance and increases insulin resistance that can be very close the physiologic symptoms of Type II diabetes that can be reversed within months of ending the cycle.
but then again i am not a doc who is on more than i am off so what the hell do i know
very good point and if ur a young punk u wont be shooting much loads aka no kids ,when u stay on for life
goku_kakarot77
New member
goku_kakarot77 said:
yea good read--bill roberts is one smart dude--shame he has the last name stolen by "he who should not be named"
eddymerckx said:Rod I'd ban you but you would probably fly to Colorado and kick my ass.
My first thought (off the cuff) is that the sides of uninterrupted use at cycle dosages would be a problem (secondary polycythemia would be a virtual guaranteed and the only to fix it would be 120 days of no exogenous androgens).
There would also be the prostate issue—may be hard to pee when it becomes the size of a cantaloupe.
Also, the soft tissue needs time to catch up to the increase in muscle strength. Never say SOFT tissue to anyone over 40.
The latest research links chronically high blood pressure and high (and ldl/hdl ratio) cholesterol to Alzheimer’s. Mine's 1.48. Healthy range 1.00 - 3.64 ...........Now.... what was the question ????
The enlargement and thickening of left ventricular wall is still a point of argument among the docs and some studies link it to dose while others link it to cycle duration ---but I think the evidence is pretty conclusive . Typical in many atheletes who NEVER use AAS.
There some evidence that the immune system is compromised and is correlated directly to the length of the cycle (but I notice that at 41 I can’t do a 16 week heavy cycle anymore—so maybe the immune system is compromised by just the intensity of workouts x length—but what the hell do I know)..... Not much!
Finally, gear decrease glucose tolerance and increases insulin resistance that can be very close the physiologic symptoms of Type II diabetes that can be reversed within months of ending the cycle. Glucose 84. Heathy range 70-100
but then again i am not a doc who is on more than i am off so what the hell do i know
You are 0 for 5 good thing you're a LAWYER!!!
halfcenturian said:eddymerckx said:Rod I'd ban you but you would probably fly to Colorado and kick my ass.
My first thought (off the cuff) is that the sides of uninterrupted use at cycle dosages would be a problem (secondary polycythemia would be a virtual guaranteed and the only to fix it would be 120 days of no exogenous androgens).
There would also be the prostate issue—may be hard to pee when it becomes the size of a cantaloupe.
Also, the soft tissue needs time to catch up to the increase in muscle strength. Never say SOFT tissue to anyone over 40.
The latest research links chronically high blood pressure and high (and ldl/hdl ratio) cholesterol to Alzheimer’s. Mine's 1.48. Healthy range 1.00 - 3.64 ...........Now.... what was the question ????
The enlargement and thickening of left ventricular wall is still a point of argument among the docs and some studies link it to dose while others link it to cycle duration ---but I think the evidence is pretty conclusive . Typical in many atheletes who NEVER use AAS.
There some evidence that the immune system is compromised and is correlated directly to the length of the cycle (but I notice that at 41 I can’t do a 16 week heavy cycle anymore—so maybe the immune system is compromised by just the intensity of workouts x length—but what the hell do I know)..... Not much!
Finally, gear decrease glucose tolerance and increases insulin resistance that can be very close the physiologic symptoms of Type II diabetes that can be reversed within months of ending the cycle. Glucose 84. Heathy range 70-100
but then again i am not a doc who is on more than i am off so what the hell do i know
You are 0 for 5 good thing you're a LAWYER!!!
see but your numbers don't count because you died three years ago and only come out at night.
eddymerckx said:see but your numbers don't count because you died three years ago and only come out at night.
300 years ago....
.
nzrodney said:
yea, but the problem is when the hematocrit gets too high (b/c both the red blood cells don;t break down as easy and extra are produces) the sides go from troublesome to dangerous--killed a bunch of cyclists in the mid 90s when they went overboard on epo (which is just a faster way of raising the hc level than androgens). when my hc hit 54 i was not a happy camper.
