Receptor Theroy

Yo you a hockey player or soccer... Anyway, I have been on for 9 months or so and found that I am increasing strength/size/weight but at a much slower rate than when I first started. If I had stopped and cycled, then I would have lost muscle and had to regain it again. I have also recently heard that receptor saturation is a myth, but not for sure. I will come off next month for 1-2 months and see what happens...

if receptor saturation was a myth then u could stay on a cycle indefinitely and gain at the same rate all the time, of course this is not the case

true you would have to use a higher dose if you always stayed on , but then you would have to do the same even if you went off and and then went back on another cycle a month or 2 later... I guess it depends on everbodies genetics..

OK...I am a soccer GK 🙂 Next...if you have really been on 9 months..can I ask what it is that you are taking. While you may start to gain more slowly, then at least you wont shrink.

if receptor saturation was a myth then u could stay on a cycle indefinitely and gain at the same rate all the time, of course this is not the case The body needs time to get use the new grow and it fights u every step of the way...in my opinion the receptor theory is bunk. read this

The Androgen Receptor Now, having a broad view of the process, let's take a closer look at the AR itself. The AR is a large protein molecule, produced from one and only one gene in DNA. There aren't lots of different kinds of receptors, as some authors claim. There are not, for example, ARs specific for oral or injectable anabolics, nor for different esters of testosterone, nor for any different kinds of AAS. The first important question to ask is, "How many ARs do you have? Is the number small or large? Can it be changed?" Since these are, in effect, little machines which are either on or off, and their effect is greater as more are activated, we want as many of them switched on as possible. There are far fewer ARs than most people realize. Some authors who are opposed to AAS doses beyond 200 mg/week say that only this amount will be accepted by the receptors in muscle, and everything past that will "spill over" and go into receptors in the skin and elsewhere. Research shows that muscle tissue has, roughly, 3 nanomoles of ARs per kg. Then your body probably has less than 300 nanomoles of ARs, grand total, let's say. Well, one 2.5 mg tab of oxandrolone supplies about 8000 nanomoles of AAS. Clearly, that's far more molecules than your body has receptors. A little math shows that all those receptors combined could bind only a small percentage of the molecules of AAS in one little 2.5 mg tab. So binding to ARs cannot appreciably reduce the concentration of AAS in the blood. Therefore, the ideas that ARs will bind most of whatever dose some author recommends, or that "spill-over" will occur beyond that, are entirely wrong. There just aren't that many receptors. Typical doses of AAS are high enough that a high percentage of the ARs are bound to AAS, whether the dose is say 400 mg/week or 1000 mg/week. If similar percentages of ARs are active – close to 100% in each case -- then why do higher doses give more results? It's a fact that they do, but there is not any large percentage of unoccupied receptors at the moderate dose. Thus, there is little room for improvement there. So at least part of the cause must be something other than simply occupying a higher percentage of receptors. And why did I pick those doses, rather than comparing normal levels with say 400 mg/week? The fact that the ARs must form dimers to be active has an interesting consequence. The mathematics are such that if two ARs must join together to form an activated dimer, and both must bind a molecule of AAS, then the square must be taken of the percentage. This means that if say 71% of receptors are binding steroid, only 50% of the dimers will be activated. Thus, at low levels, there is more room for improvement than one would think. But if say 95% are occupied, then even after squaring that, there would still only be 10% room for improvement. But actual improvement – increase in effect – seems to be much more than 10%. Anabolism increases even as the dose becomes more than sufficient to ensure virtually complete binding. Why? One popular explanation is that high doses of AAS block cortisol receptors and are thus anti-catabolic. But if this were an adequate explanation, then one could use anti-cortisol drugs together with low doses of AAS and get the same results as with high doses of AAS. This isn't the case. In fact, if cortisol is suppressed, this simply results in painful joint problems. And if the cortisol-blocking theory were true, we also would expect that persons with abnormally low cortisol ought to be quite muscular. That isn’t the case either. Three other possibilities come to mind: Possible Explanations for the Effect of High Dose Anabolic- Androgenic Steroids High doses of AAS could upregulate AR production Although activity cannot be greatly increased by increasing occupancy of existing receptors, it might potentially be greatly increased by increasing the number of receptors. This is mentioned here as a possible explanation for the effects of high dose AAS, not as an established observed fact in muscle tissue of bodybuilders. I am not aware of any such studies. Upregulation is observed from supraphysiological doses of nonaromatizing AAS in other tissues, and is observed in humans in response to resistance exercise. High doses of AAS could stimulate growth independently of the AR In muscle tissue, androgen has been observed to activate the immediate-early gene zif268 in a process not involving the AR. This activity is almost certainly related to muscle growth, and it requires high doses. Testosterone is observed to increase the efficiency of mRNA translation of cellular proteins, and this may be mediated by a mechanism independent of the AR. Nerve tissue has been observed to respond almost instantly to androgen. This cannot be a result of the AR mediated process I have described here, because that process takes much more time. Generally speaking, the hypothesis that a drug acts by only one mode of action can be tested by examining the dose/response curve. If an effect is dependent only upon the activity of a receptor, then the log response should follow a sigmoidal function (an S shaped curve). The graph would be nearly flat both at low and high doses, and approximately linear at moderate doses. At moderate doses the linear function is indeed seen. The problem is, for the range of approximately 100 to 1000 mg/week, the graph remains linear regardless of dose! By the way, this does not mean that twice the dose gives twice the effect. Rather, about four times the dose is required to give twice the effect. This response is not consistent with a simple receptor-only model; such a model is not supported by the dose/response curve. But this type of response is to be expected if there are other variables besides receptor binding. This can be explained if one or more of the mechanisms is saturated at lower levels of drug, and one or more other mechanisms do not become saturated until much higher levels of drug are used. High doses of AAS might improve the efficiency of action of ARs Not only the number of ARs is important, but also their efficiency of operation. The entire process, as was partially described above, involves many proteins, some of which may be limiting. Increases in the amounts of these proteins might increase activity dramatically. For example, ARA70 is a protein which can improve the activity of the AR by ten times. I am not aware of any study determining how ARA70 may be regulated by high doses of AAS. I cite this as an example of the type of pharmacology that may be going on, and also, incidentally, as a potential target. If you happen to see where some other drug has been seen to increase ARA70, that might be very interesting! Other proteins which can affect efficiency include RAF, which enhances the binding of the AR to DNA by about 25-fold; GRIP1, and cJun. None of these, unfortunately, could themselves be taken as drugs. But you can see that there are many ways by which AR activity could change besides any "upregulation" or "downregulation" of receptors. Authors who make such claims as the be-all and end-all of their steroid theories essentially do not know what they are talking about. Without specific evidence – without actual measurement of AR levels – it is always unjustified to claim that "androgen receptor downregulation must have occurred," especially on the basis of anecdotal evidence. Actual measurements are always lacking from such claims. Nor is it justified to assume that increasing the occupancy of ARs is the only way to increase the effect of androgens, as we have seen. It is justified, on the basis of real world results, to say that high dose AAS are more effective than low dose AAS, and certainly more effective than natural levels of AAS. This is true even if use is sustained over time. That however is not consistent with any claims of downregulation of androgen receptors in response to high doses of AAS. It also is justified both from bodybuilding experience and from scientific evidence that low AAS doses, such as 100 or 200 mg/week, will generally not give much results for male athletes. Next, we will consider regulation of the androgen receptor more closely. There have been many opposing claims concerning this. Which claims are valid? How should these theories affect an athlete’s planning? Overview of Regulation Meaning of regulation "Regulation" of a receptor refers to control over the number of receptors per cell. "Sensitivity," in contrast, refers to the degree of activity each receptor has. It is a possible in many cases for the receptors of a cell to be sensitized or desensitized to a drug or hormone, independently of the number of receptors. Similarly, it is possible for the receptors to upregulate or downregulate, to increase or decrease in number, independently of any changes in sensitivity. If sensitivity remains the same, then upregulation will yield higher response to the same amount of drug or hormone, and downregulation will result in less response. So if we are discussing androgen receptor regulation, we are discussing how many ARs are present per cell, and how this may change. Changes in regulation must, of necessity, be between two different states, for example, levels of hormone. In the case of bodybuilding, we are interested in supraphysiological levels vs. normal levels (or perhaps, a higher supraphysiological level vs. a lower supraphysiological level.) In most research that is done, the comparison is often between normal levels and zero levels, or the castrated state. We may describe regulation with the two levels being in either order. Upregulation as levels decrease from normal to zero is the same thing, but in the reverse direction, as downregulation as levels increase from zero to normal. The term which would be used will depend on context, but does not change meaning, so long as the direction of change in level of hormone is understood. If upregulation occurs as levels decrease from normal to zero, as is probably the case in some tissues, this would imply nothing about what may happen as levels increase beyond normal. It does not prove that downregulation would occur. It would be a serious error to take a study comparing normal levels and zero levels and use that study to argue the effect of supraphysiological levels. Unfortunately, such mistakes are commonly made by authors in bodybuilding. Forms of regulation Broadly speaking, there are three things that control the number of receptors. To understand them, let’s quickly review the life-cycle of an individual AR. There is a single gene in the DNA of each cell that codes for the AR. In the transcription process, the DNA code is copied to mRNA. The rate (frequency) of this process can be either increased (promoted) or decreased (repressed) depending on what other proteins are bound to the DNA at the time. Increase or decrease of this rate can be a form

the rest is too long but this the conclusion Conclusions from Bodybuilding Observations I find it rather unreasonable to think that the most likely thing is that athletes who have been on high dose AAS for years, and are far more massive than what they could be naturally, and who are maintaining that mass or even slowly gaining more, could possibly have less androgen receptor activity than natural athletes or low-dose steroid users. It might, hypothetically, be possible that their AR activity is the same, and the extra size due to steroids is due entirely to non-AR mediated activities of the androgens. However there is no evidence for that and it seems unlikely. I believe the most logical possibility is that these athletes are experiencing higher activity from their androgen receptors than natural athletes, or low dose steroid users, are experiencing. Since the majority of androgen receptors are occupied at quite moderate levels of AAS, the explanation cannot be simply that a higher percentage of receptors is occupied, with the receptor number being the same. That would not allow much improvement. In contrast, upregulation would allow substantial improvement, such as is apparently the case (unless non-AR mediated activities are largely or entirely responsible for improved anabolism, which would be an entirely unsupported hypothesis.) Upregulation in human muscle tissue, in vivo, is not directly proven but seems to fit the evidence and to provide a plausible explanation for observed results. I leave the matter, however, to the reader. Weigh the evidence, and decide if downregulation, as popularly advocated, is supported by science, or by what is experienced in bodybuilders.

Good post Dotres.....from what I have seen and experienced so far I think the upregulation theory is the most viable explanation..........