Androgen Receptors (AR) - The main determinant of progress

We all likely know someone who frequently goes the gym, maintains a healthy diet, and has extensive knowledge about lifting and bodybuilding but still appears weak and makes little progress even after years of training. They might even be using AAS, but all it does to their body is back acne with little factual benefits. Unless they are competing in a sport where muscle development and strength are unimportant, we may attribute their lack of progress to "poor genetics." However, what does it really mean to have these so-called "bad genes"?

"Bad genes" - under this phrase, are hidden diverse factors:
> low expression of genes, which are responsible for muscle growth, e.g., 582Ser or high expression of genes responsible for, i.a., myostatin secretion like MSTN (read more about genes in sport in the following article: https://www.patreon.com/posts/age-of-gene-role-36882973
> high cortisol and low secretion of androgens (which may be regulated via i.a., lifestyle and diet)
> low response of androgen receptors in muscles and bones (due to their low sensitivity, density / quantity in the muscle tissue)

ANDROGEN RECEPTORS (AR) - belongs to the group of nuclear receptors (ligand-responsive transcription regulators family) that are activated by binding with any of the androgenic hormones (testosterone, DHT, DHEA, and their derivatives). It means that every time one of the androgenic hormones binds to the receptor, it becomes activated and translocated to the hormones-responsive part located in the nucleus (illustrated in the picture below)

The entire process results in up/down-regulation of specific gene transcription. It means that at this moment, it becomes possible to induce all of the effects associated with masculinization, so response to androgens, e.g., production of proteins responsible for muscle growth (indirectly improved synthesis), increased IGF-1 production, body hair growth, etc.

THE LOCATION OF ANDROGEN RECEPTORS

Androgen receptors are located in the tissues of the whole body (bone / muscle / skin / hair / fat tissue / testes / prostate / brain) and therefore have a vast influence on the entire organism (immune / cardiovascular / nervous / reproductive system / cognition) and will also be related to the occurrence of i.a. acne, balding, or enlarged prostate gland.

The fact that ARs are located around the whole body with diverse density and in various quantity determines which tissue will respond to their activity.

A person with more ARs in the muscle tissue will progress much faster and easier than someone with a low quantity of ARs in the muscle tissue. If someone has more of highly responsive ARs in skin tissue he will be much more prone i.a. skin disorders, e.g., acne or skin tumor.

Many ARs are often located on deltoid muscles. Therefore, a person highly responsive to androgens will often have well-defined, rounded delts (even without training regularly). Also, most athletes who use AAS (anabolic-androgenic steroids) will first notice rapid changes in this body part.

THE SENSITIVITY OF ANDROGEN RECEPTORS

The second primary determinant of how efficiently ARs respond is their sensitivity. The N-terminal domain, which is essential for the proper functioning of AR, can be arranged in several combinations in various length. It depends on the trinucleotide - CAG (cytosine, adenine, guanine). This CAG combination is usually repeated 11 up to 33 times - The shorter it is, the faster information can be transferred (between androgen and DNA)  and with higher precision. The more this sequence is repeated, the slower information pieces will be transferred, and the worse result will be obtained.

Worth knowing: men with low sensitivity of their androgen receptors (so a high amount of CAG repetitions) will have low testosterone symptoms, i.a.: infertility, low bone mineralization, insulin resistance, worsened well-being (prone to depression), higher body fat. On the other hand, men with highly sensitized androgen receptors may be inclined to balding, more aggressive, or have a low HDL level.

These two factors: density and sensitivity, will determine how a person reacts to androgens activity (including hormonal doping) and how fast they progress (in the context of sport). It can be easily noticed if you know two guys who are "on gear" (even better if they inject the same agents of the same brand, e.g., 500mg of testosterone cypionate per week). One of them can progress twice or even faster than the other while being on the same caloric surplus and performing the same well-planned training.

AFFINITY TO ANDROGEN RECEPTORS

Androgens have various affinities to androgen receptors. What does it mean?

[analogy] Imagine that you are playing darts, and your nickname is Testosterone (androgen). You have one dart (affinity), and are trying to hit the bullseye (androgen receptor). When you hit it, you receive 50 points (the strength of the androgenic effect). Unluckily, your opponent is the famous Trenbolone (androgen). He has 5 darts (affinity), and every time he hits the bullseye (androgen receptor), he receives 250 points (the strength of the androgenic effect)... quite unfair, isn't it?

That is how affinity works. The higher affinity of androgen, the higher chance that it will join to a particular androgen receptor (the more darts / more shots you have). The higher its anabolic-androgenic potential (the more points you get), the stronger effects it induces whenever it activates the receptor (hit bullseye).

Following the example - The higher sensitivity of androgen receptors, the bigger the bullseye is. The highest density, the more bullseyes can be found on a dartboard (correct, in this beta game, there can be more of them). Therefore, if the bullseye is small, and is only a single one located in the middle of the dart board, even a great player like Trenbolone will have a hard time hitting it despite having many darts.

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If you have trouble understanding the scientific terms, read the above analogy starting with "Imagine." 

I tried to provide as brief explanation as I could. After reading the whole article, I hope that it is in 95% clear how ARs work and why they determine the progress in sports. If you have questions, freely ask me in the comment section.