+ 1 Up regulation of androgen receptors - Discussion
Just bored so I would put a thought up.
Its a well known myth that steroid use down regulates androgen receptors (AR). Steroids actually do the opposite – they up-regulate your androgen receptors. There are more than a few indirect studies on this (if you care http://www.ncbi.nlm.nih.gov/pubmed/21427060 , Endocrinology (1990) 126 1165 ect).
The premise of such findings are that AR are constantly being turned over. When unattached to an androgen they have a 1/2 life of 3 hours and are ultimately replaced with new ones. But the presence of an androgen they become more sensitive, their half life is doubled and the amount of new receptors being formed also increases substantially. Thus steroid use increases the number and sensitivity of AR's.
So if steroids upregulate AR, then should we be concerned post PCT when baseline T levels are lower than before steroid use (when I mean lower, I mean lower but still within range). If AR are 'extra' sensitive post cycle, then T levels would be lower than previous baselines, as less T is needed to achieve the same baseline effects. Thats is, pre-steroids you had levels of 600 (300-1200), but after using steroids you can only ever achieve (off-cycle) say 400 (300-1200). In these circumstances we are not talking about someone 'shut down' just with lower baseline T levels.
Does this explain why so many guys who do gear have lower T levels when they are 'going natural', but feel fine?
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im not the most versed in endocrinology but i have a basic understanding...to start with, i believe that lower t levels after cycle are due to decreased production of endogenous androgens like the article says (decreased steroidogenesis in leydig cells). i presume the reason why some people feel fine at lower levels is due to the amount of free testosterone. This feeling could be do in part by the extra AR available to bind but i believe after cycle there is a down regulation of AR production so when exogenous androgen decreases then the rate of production and total number of the AR's also decreases. now on to the whole binding/sensitization thing. I think people confuse up regulation/downregulation with binding affinity or desensitization sensitization. when you inject exo test you up regulate receptor production and increase binding affinity, or the ability of the target hormone to processed by the receptor. as with any body process, constant up regulation cannot be supported due to protein damage. after this damage has occured the AR will desensitize or lose its binding affinity while the transcription errors are attempted to be fixed. During this time they are either fixed or disposed of. If you keep administering more and more exo androgens there will be a point in which the repair/reproduction of receptors will not be able to keep up. I expect that when people talk about diminishing gains towards the end of a long cycle, this is the underlying cause. If you want to read more about the subject check out nuclear receptor regulation. Androgen receptors are from the larger class, nuclear receptors. Since there are not too many in vivo studies of androgen receptors, anything on nuclear receptors can be studied for the same mechanism. Like I said, i am not expert on the subject but from my research this is my understanding and my .02