T Nation

The AR Gene Polymorphism

I searched about and couldn’t seem to find anything related to these ideas on T-Nation.

I was wondering if any had read this article or had heard of these paticular phenomenas. I would certainly be interested in your feedback -either way.

The following is an article I found here:
steroidsprofiles.com/article/info/246

STEROIDS…RISK?
It is a fact that each bodybuilder reacts differently to anabolic steroids. On the one hand, we have bodybuilders whose health seems to improve while on steroids. They grow muscle, lose fat, feel better and much more confident.

On the other hand, some lifters do not seem to react in any positive way. They lose hair, turn purple, get easily upset, experience problems with urination and suffer from hypertension. As far as muscle gains are concerned, they seem completely insensitive to the anabolic actions of steroids.

The androgen receptor gene polymorphism

These discrepancies in reactions to anabolic steroids are not an unexplained phenomenon. A high density of muscles’ androgen receptors (AR) predisposes the gear users to more fully benefit from steroids. But if all your cells except your muscles are endowed with a high density of androgen receptors, the incidence of side effects are likely to be high.

Steroid metabolism or destruction is another important variable. Testosterone can be converted into plenty of different hormones such as estrogens or dihydrotestosterone. The higher the conversion rate, the more side effects you will suffer from and the lesser anabolic actions you will benefit from. But there is more to it!

Many assume that an androgen receptor is an androgen receptor. AR are supposed to be all alike and equally effective. Recent studies suggest that each individual does not possess the exact same androgen receptors. Polymorphisms do exist. One of the most studied polymorphism is the CAG repeats.

Long or short CAG repeats?

The gene ordering the production of the androgen receptors is polymorphic as it can contain a various number of CAG repeats. C stands for cytosine, A for adenine and G for guanine. In normal people, the CAG repeats can range from 6 to 39.

It means that in our gene encoding androgen receptors, the CAG triplets can be repeated 6 times up to 39 times. It seems obvious that each polymorphism will produce a slightly different kind of androgen receptors.
Up to 23 repeats, one is considered as having short CAG while above 23 one belongs to the long repeat group.

What does that mean for me?

People with short repeats are the most sensitive to the androgenic actions of testosterone. If, at a young age, you suffered from acne, hirsutism and baldness, then your CAG repeat is likely to be short. People having the longest repeats are less sensitive to the androgenic actions of testosterone. If you never suffered from the above described side effects of your own testosterone, chances are you belong to the long CAG repeat group.

You may have heard of insulin resistance You may say you are testosterone resistant because of a mutation of your androgen receptors. They do not like testosterone as much as the androgen receptors encoded by the gene carrying shorter repeats. This hyposensitivity does not sound good. Or does it?

CAG repeat length and muscle mass

Men with long CAG repeats may be expected to carry less muscle mass due to this more or less pronounced testosterone resistance. Surprisingly, scientific studies do not concur. In fact, they demonstrate the opposite. Untrained men with long CAG repeats carry around 6% more fat free mass than men with short CAG repeats. It suggests that men with long CAG repeats are testosterone insensitive all over their body except on their muscle cells.

As a result, their own testosterone will produce less side effects but more anabolic activity. Due to their partial insensitivity to androgens, those men tend to produce more testosterone, too. So, natural bodybuilders with a long profile are luckier than bodybuilders with short CAG repeats.

What will happen while on steroids? The fact they will benefit more from their anabolics is controversial. Bhasin found that in testosterone users, “the length of CAG tract was only a weak predictor of change in lean body mass”.

But do not be surprised to experience more side effects due to steroids if you fit the short CAG profile. The muscle mass gain/side effects ratio is likely to be better in bodybuilders with long CAG repeats.

Think long term!

Men with short CAG repeats are more likely to suffer from prostate cancer and cardiovascular diseases as they grow older. So, they should really think twice before using steroids. In any case, protect yourself by using a potent 5-alpha reductase inhibitor (except maybe while on Nandrolone).

Studies have shown that men with long CAG repeats have a higher risk of suffering from breast cancer compared to men with short repeats. This is probably due to the fact that estrogen production tends to be higher in men with long CAG repeats. So, do not take any risk! If you choose to use steroids, a strong anti-aromatase may help you reduce the incidence of gynecomastia and future estrogen-related cancers. Men with long repeats also experience a higher incidence of reproductive problems. If you do and if it is a trouble, a 5-alpha reductase inhibitor may not be a good idea as it may exacerbate erectile problems. If it does not, use one if you can afford it.

Practical applications for bodybuilders with a short CAG repeat profile :

One cannot alter its repeat profile as your number of CAG triplets is genetically determined.
You can only attempt to fight the androgenic side effects.
If you experienced visible side effects out of your own testosterone at an early age, think twice before using steroids. You are at risk in the long run even if you stay steroid free.

It is not because your muscles do not seem to respond much to steroids that damages are not induced to the rest of your body. Try to play it safe and use as much protective measures as possible.

Use the weakest anabolics possible and stay away from the potent androgenic ones.

Use a 5-alpha reductase inhibitor while on and while off steroids.

Practical applications for long CAG repeat bodybuilders:

Do not assume that with this profile, you will never suffer from steroid side effects. You are only statistically less at risk.

Your priority is to inhibit estrogen
If it does not induce any erectile problem, you may want to use a 5-alpha reductase inhibitor, too.

REFERENCES:

Buchanan G, Yang M, Cheong A, Harris JM, Irvine RA, Lambert PF, Moore NL,
Raynor M, Neufing PJ, Coetzee GA, Tilley WD. Structural and functional
consequences of glutamine tract variation in the androgen receptor.
Hum Mol Genet. 2004 Aug 15;13(16):1677-92
Sawaya ME, Shalita AR. Androgen receptor polymorphisms (CAG repeat lengths)
in androgenetic alopecia, hirsutism, and acne.
J Cutan Med Surg. 1998 Jul;3(1):9-15.
Walsh S, Zmuda JM, Cauley JA, Shea PR, Metter EJ, Hurley BF, Ferrell RE,
Roth SM.
Androgen receptor CAG repeat polymorphism is associated with fat-free mass
in men.
J Appl Physiol. 2005 Jan;98(1):132-7
Krithivas K, Yurgalevitch SM, Mohr BA, Wilcox CJ, Batter SJ, Brown M,
Longcope C, McKinlay JB, Kantoff PW. Evidence that the CAG repeat in the androgen
receptor gene is associated with the age-related decline in serum androgen
levels in men.
J Endocrinol. 1999 Jul;162(1):137-42.
MacLean HE, Brown RW, Beilin J, Warne GL, Zajac JD. Increased frequency of
long androgen receptor CAG repeats in male breast cancers.
Breast Cancer Res Treat. 2004 Dec;88(3):239-46.

Genetic polymorphisms are different than receptor polymorphisms (more commonly called isoforms). It is true that there are varying isoforms of all androgen (and estrogen, etc.) receptors, and that each one has a slightly different response once “activated.” I haven’t read any of the references yet (I definitely will as it sounds interesting), but from my experience in the field it seems like the author read the “conclusion” portion of the abstracts and didn’t fully understand what he was reading. He’s mostly got the right idea, but definitely doesn’t understand what he’s actually saying. If I get around to checking them out (perhaps this weekend) then I’ll post my comments.

Speaking of prostate cancer and receptor isoforms, this is a good read that may open up many peoples’ eyes to the complexity of this topic.

If anyone is seriously interested in the full text I can send them a copy, solely for educational purposes via copyright laws.

This post was flagged by the community and is temporarily hidden.

Orgh, my name ish john merrick, I’m very pleeashed to meet you

(do I win?)

[quote]bushidobadboy wrote:

Yesh Pleash![/quote]

Sent.

Thanks for the replies thus far.

I suppose what I found intriguing about the article, was the idea that some folks may just be ‘non-responders’ to the anabolic inducing properties of AAS.

I mean I’m sure we have all seen this phenomenon before, haven’t we?

Some folks simply do not seem to benefit from gear -at least not to the extent that their training partners or others might.

I just find it strange that some guys ‘blow-up’ on the smallest amounts of AAS while other guys just cannot seem to put on a pound.

Now typically we might want to say that the diet of these ‘non-responders’ is way off or their training lacks the appropriate intensity. And indeed those may be valid points.

However, considering that many of these compounds were designed for and tested on subjects suffering from muscle wasting type diseases…one would think that the responsible use of AAS would promote at least modest growth in healthy individuals for sure. That’s not always the case though.

Perhaps the author of this article did get the science all wrong. I do hope you get the chance to look over the references Schwarzenegger. I am greatly interested in your opinion.

I do tend to think there is some validity to what the author has pointed out though. Even if he has misunderstood the reasons it occurs.

[quote]Schwarzenegger wrote:
Genetic polymorphisms are different than receptor polymorphisms (more commonly called isoforms). It is true that there are varying isoforms of all androgen (and estrogen, etc.) receptors, and that each one has a slightly different response once “activated.” I haven’t read any of the references yet (I definitely will as it sounds interesting), but from my experience in the field it seems like the author read the “conclusion” portion of the abstracts and didn’t fully understand what he was reading. He’s mostly got the right idea, but definitely doesn’t understand what he’s actually saying. If I get around to checking them out (perhaps this weekend) then I’ll post my comments.

Speaking of prostate cancer and receptor isoforms, this is a good read that may open up many peoples’ eyes to the complexity of this topic.

If anyone is seriously interested in the full text I can send them a copy, solely for educational purposes via copyright laws.[/quote]

Kinda my assessment as well. But I’d really like that full text!

It’s conceivable that the gene polymorphism could lead to receptor isoform differences, but not really a direct cause and effect thing.

@Aragorn

PM me your e-mail if you want the article.