Androgen Receptor Regulation

Jun 26, 2020

Androgen Receptor Regulation

Having in mind the importance of androgen receptors in processing steroids, it is no wonder that many steroid users and athletes are concerned about the amount of receptors they can activate and if steroid usage will lead to the decreasing number of AR. The fact is that we have fewer ARs in our body than we probably imagine. Their number is finite and they are either completely activated or completely passive, there is no mode which is somewhere in-between. Many theories suggested that increased doses of steroids can lead to androgen receptors downregulation, which is a nightmare for a regular steroid user. Since this topic causes so much fuss and worry, it’s time we address it from a scientific point of view.

Science and AR Downregulation

One of the most frequent theories about using steroids, especially in larger doses, is that the androgen receptors, necessary for binding AAS, downregulate as a result of steroid consumption. If you try to lookup this topic online, you will find many articles about it, and many forums where people discuss this topic. The main issue is the fact that users base their steroid consumption pattern on these false theories without looking into actual research.

This article will go into details regarding ARs regulation, and explain why such theories don’t have the basis in science and shouldn’t be taken for granted. With regards to this topic, you will be able to understand the following:

• There is no scientific evidence that androgen receptors downregulate in the muscle tissue as a result of taking steroids in greater than recommended doses

• In the cases where downregulation was noticed, the probable cause was estrogen level or inaccurate method of establishing AR regulation. Therefore, the results of the test were either inapplicable to supraphysiological use of androgens or inaccurate.

• In fact, different reliable methods and experiments have concluded that overuse of AAs leads to upregulation instead of downregulation of ARs.

• AR downregulation as a result of supraphysiological use of androgens does not agree with real world results obtained by professional athletes in practice, whereas upregulation perfectly fits real world results. It is also worth mentioning that a neutral position, where levels in human muscle might be observed as unchanged as a result of high levels of steroids, is not disproven.

• The arguments trying to point out to the ARs downregulation are based on false theory which are easily overturned in practice. Every user who ever tried intense consumption of steroids can testify to the fact that results were greater. Also, researchers who actually followed what happens inside our organism at the times of greater usage of steroids concluded that ARs either stay on the same level or upregulate.

Meaning of Regulation

"Regulation" of androgen receptors refers to the control over the number of receptors per cell. On the other hand, "sensitivity," refers to the degree of activity each receptor is able to accomplish. It is possible in certain cases for the receptors to be sensitized or desensitized to a substance or hormone, independently of the number of receptors. Also, it is actually possible for the receptors to upregulate or downregulate and to increase or decrease in number, independently of any changes in sensitivity. If sensitivity remains on the same level, then upregulation will yield higher response to the same amount of substance or hormone, and downregulation will result in decreased response.

In this article, we are addressing the issue of androgen receptor regulation, which means how many ARs exist per cell and how this can change and under which circumstances.

Changes in regulation have to happen between two different states of, for example, levels of hormones or substances. In the case of bodybuilding, we are interested in supraphysiological levels vs. normal levels. If you have a look at the research which is published on this or similar topic so far, you will be able to see that the comparison is most frequently 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 depends on context, but the meaning remains the same, as long as the direction of change in level is understood as increasing or decreasing.

If upregulation happens in the case of levels dropping from normal to zero, as is could be the case in some tissues, this would suggest nothing about what could probably happen as a consequence of levels going up beyond normal. It does not prove that downregulation would occur. It would be a serious error to have a look at the research which compares normal levels and zero levels and then use this research to explain the effect of supraphysiological levels. And yet, these logical fallacies frequently happen among authors who write about steroids and bodybuilding.

Forms of Regulation

In general, there are three things that are able to control the number of ARs. In order to understand the process of regulation, we need to take into the account the life-cycle of an any androgen receptor.

Only one gene is our DNA chain in our cells codes for the AR. During the transcription process, the DNA code gets copied onto mRNA. The speed and frequency of this process can be either increased-promoted or decreased-repressed). Which one of these occurrences will happen, will depend on other kinds of proteins which are bound to the DNA at the time of the process. Increase or decrease of this frequency can be a form of regulation: the more AR mRNA is produced, if other factors remain unchanged, the more ARs there will be. However, other factors rarely remain completely unchanged.

If efficiency on its maximum of 100%, each mRNA will be used by a ribosome to produce an androgen receptor, which is in its essence, a protein molecule. The process of making protein from the mRNA code is called translation. In practice efficiency doesn’t reach 100%. Changes in efficiency of translation can also be one of the forms of regulation of ARs.

The third important contributing factor to regulation is the rate of loss of androgen receptors. If the cell produces certain amount of receptors per hour, and their half-life is around 8 hours, then the number of available receptors will be higher than if receptors are produced at that same rate but their half-life is shorter, for example only 4 hours. This means that the control of rate of turnover, or in increase or decrease in half- life, can be one of the possible forms of AR regulation.

Summary

Androgen receptors are crucial for processing steroids and getting the results we want from them. The fact that these receptors are limited in their amount per cells makes them even more precious. Therefore, it is no wonder that so many authors writing about bodybuilders addressed the topic of downregulation and upregulations of ARs. However, many of them concluded that intense use of steroids leads to downregulation which in turns causes decreasing effects of steroids. This is an unfounded conclusion which is easily refuted in practice. The real issue with such claims is that many steroid users will base their steroid cycles and consumption plan on the false facts. This is why it is so important to understand ARs regulation and how upregulation and downregulation works in practice.

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