T Nation

Reduced Density of Androgen Receptors?

I just read an article with the following quote:

“The first steroid cycle you will do is usually the most effective in terms of muscle mass gains. Your muscles are full of testosterone receptors. They are therefore very sensitive to extra male hormones. Your second cycle will be a bit less effective. And it gets worst and worst. In order to counteract this diminishing effect of steroids, your only solution is to increase the dosages.”

Could the reduction in the sensitivity of testosterone receptors be permanent/long-term following a cycle, as the quote above suggests? Is that really the reason that a first cycle seems to be the best? I was thinking that the first cycle was the best simply because by the time of the second cycle, the user is already well past his natural maximum. This quote suggests otherwise. It seems to predict that someone who has previously done many cycles, but subsequently lost all his gains, would now be less sensitive to testosterone. Does that seem likely? If so, do you just accept it as one of the drawbacks of using steroids?

Or if the receptors’ sensitivity returns, then how quickly might it return? It sounds like it might take a lot longer that it takes testosterone production to return, if this is the reason that subsequent cycles are less productive than the first.

Thanks guys.

Receptor downregulation was something I was thinking about lately.

I always kind of dismissed the idea as bunk to be honest and, like you, believed that the reason people did not experience the same gains from their subsequent cycles was that with each cycle they were getting further past their genetic limit and it became more difficult for them to gain…but I have experienced evidence to suggest the theory may have some merit…

I do recall one cycle in particular where post cycle I got sick and within 8 weeks had dropped back to about the same level that I had been pre-cycle. Mosst things were the same as the pre-cycle starting point (bodyfat, strength, weight)

So, I decided that I would go back on the same cycle again expecting that I would get the very same gains this time. (I mean, the receptor downregulation theory is bunk, right?)Everything else (diet, training, lifestyle etc) was the same as when I was on before also. It was also the same gear I was using (I know it was the very same as I brew all my own gear)

Guess what? The cycle was not NEARLY as succesful as it was the first time round. The gains were not even remotely as good as they were the first time. It surprised me a LOT.

Was this due to receptor downregulation? I dont know, but it certainly got me thinking that there may be something behind it…

Perhaps instead of having receptors permanently down-regulated after beginning AAS, the speed and efficiency of adaptation is greater. This makes more sense and mimics other physiological phenomena than does permanent downregulation.

If I start using AAS and my receptors are down-regulated, then after the cycle they should not return to “normal,” meaning I shouldn’t be able to gain nearly any muscle or have any appreciable response to AAS in any tissues (sex drive also seems to be boosted greater during the first cycle, as does other AAS-induced side effects). However, after coming off the cycle you return to your normal pre-cycle functioning. Unfortunately the next cycle doesn’t seem as strong.

I think this sort of acts like the immune system. You may get the flu the first time and be miserable. The next time you get the flu you will get sick, but not nearly to the extent as the first time, and it certainly doesn’t last as long. This sort of mirrors subsequent AAS cycles, so it suggests there is an enhanced adaptation response, or quickened attainment of homeostasis with higher androgen levels, after the first cycle.

I won’t get it it, but this idea uses the same principles as does Prisoner’s test taper protocol. Unfortunately we don’t know for sure what the mechanism really is, only speculation based on physiological principles in other systems.

That’s my take on it at least.

don’t receptors upregulate?

[quote]Schwarzenegger wrote:
Perhaps instead of having receptors permanently down-regulated after beginning AAS, the speed and efficiency of adaptation is greater. This makes more sense and mimics other physiological phenomena than does permanent downregulation.

If I start using AAS and my receptors are down-regulated, then after the cycle they should not return to “normal,” meaning I shouldn’t be able to gain nearly any muscle or have any appreciable response to AAS in any tissues (sex drive also seems to be boosted greater during the first cycle, as does other AAS-induced side effects). However, after coming off the cycle you return to your normal pre-cycle functioning. Unfortunately the next cycle doesn’t seem as strong.

I think this sort of acts like the immune system. You may get the flu the first time and be miserable. The next time you get the flu you will get sick, but not nearly to the extent as the first time, and it certainly doesn’t last as long. This sort of mirrors subsequent AAS cycles, so it suggests there is an enhanced adaptation response, or quickened attainment of homeostasis with higher androgen levels, after the first cycle.

I won’t get it it, but this idea uses the same principles as does Prisoner’s test taper protocol. Unfortunately we don’t know for sure what the mechanism really is, only speculation based on physiological principles in other systems.

That’s my take on it at least.[/quote]

interesting…

[quote]Schwarzenegger wrote:
Perhaps instead of having receptors permanently down-regulated after beginning AAS, the speed and efficiency of adaptation is greater.
[/quote]

Let’s hope so, anyway! I searched PubMed, but couldn’t find any evidence one way or another. But whichever explanation is correct (long-term reduction in sensitivity to testosterone vs. long-term reduction in sensitivity to supra-physiological levels of testosterone), it seems pretty likely that AAS causes long-term changes to receptors.

I’m going ahead with my cycle regardless, of course, but I think this issue is worth noting. It’s humbling to see how much about physiology remains unknown.

Does anyone have further information on the long-term effects of AAS on receptors?