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Androgen, PA, mTOR Relationship Question


#1

I feel like an idiot.

I’m so fascinated with the biochemical science of muscle growth, but I’m finding that I am simply not very adept yet at deciphering the technical documentation available out there. My biochemistry and biology prowess is sorely lacking.

As an engineer, I see things systematically. But to understand the system, one has to understand some of the nitty gritty details, details that are specific to the genre one is trying to analyze systematically. I see things as I/O signals, mathematical transfer functions, and computational logic. Amazingly, so much biology can also be seen this way, but the technical documentation isn’t written with engineering in mind (as it shouldn’t) and the jargon requires alot of interesting research.

For the life of me, I am having a hard time knowing if what I’m researching is being properly interpreted by me. In this case, its the relationship between androgen (testosterone for example) and mTOR.

The more I look at mTOR, it appears that it is the primary governor of protein synthesis of which muscle growth is under. Just mTOR. It appears that androgens and related hormonal influences govern signally of Akt, but ultimately Akt is yet another stimulator of mTOR for muscle growth.

I have indicated in another post the “equation” I believe governs muscle growth:

muscle growth = f[mTOR]

  • This is to be read as “muscle growth equal a function dependent upon mTOR signaling”.

mTOR = summation[leucine_concentration, growth_factors, PA, other, A, B, C, D]

where

  • mTOR is mTOR signal amplitude
  • summation […] is a summation function
  • leucine_concentration is, yes, the leucine concentration in blood
  • growth_factors are things like androgen (testosterone) concentration, IGF-1, insulin concentration, growth hormone concentration, etc. Again, it seems like androgens primarily contribute to mTOR via stimulation of Akt.
  • PA is phosphatidic acid concentration produced by muscle mechanical work (endogenously) or by supplementation (m-PA) exogeneously
  • other is any other contributor
  • A is the leucine concentration “tuning factor”.
  • B is the growth factor “tuning factor”.
  • C is the PA “tuning factor”
  • D is the other “tuning factor”

To exand the equation, it would look like this:

mTOR = Aleucine_contration + Bgrowth_factors + CPA + Dother

IF I’m right about this (massive simplification of course), then the question I have is this: is it possible to realize appreciable muscle growth (protein synthesis) WITHOUT adequate testosterone (androgen) levels?

It all comes down to the values of A, B, C, and D doesn’t it? If factor B is much much bigger than A, C, or D for example, then that would mean with limited androgen level, mTOR signal will have a low amplitude. If we take massive amounts of PA, but the factor C is biologically a small value, then it still might not raise the mTOR amplitude to what we need it to be to realize appreciable growth.

I need some of you smart guys/gals to help me out here. Consider it a civic duty to help an imbecile from following the wrong path of thinking that leads to further and continued frustration!

Thanks.

  • Bewildered Buffd

#2

Buffd, if you’re an idiot, I shouldn’t be allowed to walk down the street without a helmet.

You seem to have a handle on this stuff way more than most. Drop that post on BB.com and see if anyone can even read it, let alone explain it.

I’d love to hear the response, hopefully from the Dr.'s in the house. I’m just as curious as you are. I wish I could be more helpful.


#3

This was an unintentional double post. So I’ll add something instead of waste the space.

My only other thought was this:

“Over thinking, over analyzing separates my body from my mind.”

Breath, you’ll get it.


#4

Hahaha so true.


#5

I really like that equation, but I really think is far oversimplifying things.

Some other important factors would be anabolism vs. catabolism. So f[mTOR] > f[hungryx] for however great a time to produce gains in LBM.

Meanwhile I think there are other important factors here, and I think creating a more of a chemical equation/equilibrium and computer program type model is what would ultimately be best representative of the gene signaling and cellular level protein encoding.


#6

[quote]hockechamp14 wrote:
I really like that equation, but I really think is far oversimplifying things.

Some other important factors would be anabolism vs. catabolism. So f[mTOR] > f[hungryx] for however great a time to produce gains in LBM.

Meanwhile I think there are other important factors here, and I think creating a more of a chemical equation/equilibrium and computer program type model is what would ultimately be best representative of the gene signaling and cellular level protein encoding.[/quote]

Yep. You are absolutely right: the “equation” is very lacking and simplistic. But the point wasn’t getting it exactly right…it was wondering if the constituents, in general, were right. In this case the hypothesis that androgen’s contribution to muscle synthesis was primarily through the mTOR pathway via its “strength” of signal in the summation.

I really asked this, because I wonder if spiking one’s peri-workout period with a fast acting anabolic like DBol combined with m-PA (the DBol 2 hours before training; the m-PA one hour prior) and Indigo (30 minutes before training) and with fast acting peri-workout nutrition would be the bomb. i.e. could the addition of a “small” amount of anabolics amplify the mTOR signaling linearly…or exponentially?


#7

[quote]buffd_samurai wrote:

muscle growth = f[mTOR]

  • This is to be read as “muscle growth equal a function dependent upon mTOR signaling”.

mTOR = summation[leucine_concentration, growth_factors, PA, other, A, B, C, D]

where

  • mTOR is mTOR signal amplitude
  • summation […] is a summation function
  • leucine_concentration is, yes, the leucine concentration in blood
  • growth_factors are things like androgen (testosterone) concentration, IGF-1, insulin concentration, growth hormone concentration, etc. Again, it seems like androgens primarily contribute to mTOR via stimulation of Akt.
  • PA is phosphatidic acid concentration produced by muscle mechanical work (endogenously) or by supplementation (m-PA) exogeneously
  • other is any other contributor
  • A is the leucine concentration “tuning factor”.
  • B is the growth factor “tuning factor”.
  • C is the PA “tuning factor”
  • D is the other “tuning factor”

To exand the equation, it would look like this:

mTOR = Aleucine_contration + Bgrowth_factors + CPA + Dother

[/quote]

I, too, am a computer engineer fixated on increasing strength and muscle mass who unfortunately lacks any formal physiology background. :confused:

Hmm, very interesting theory you have, but I would imagine that mTOR wouldn’t be a simple summation, due to interplay among the variables, as well as saturation.


#8

Also, again excuse my physiological ignorance, but does mTOR signal protein synthesis in a “binary” way(adequate mTOR -> signal protein synthesis -> build muscle, inadequate mTOR -> no protein synthesis -> no muscle built) or in a linear way(more mTOR -> greater signaling -> greater degree of muscle being built).

Also, if it is binary, is the signaling of protein synthesis edge(signal protein synthesis when I go from low to high) or level(continuously signal while high) triggered?

Please excuse all the computer analogies… :slight_smile:


#9

[quote]thenewguy wrote:
I, too, am a computer engineer fixated on increasing strength and muscle mass who unfortunately lacks any formal physiology background. :confused:

Hmm, very interesting theory you have, but I would imagine that mTOR wouldn’t be a simple summation, due to interplay among the variables, as well as saturation.[/quote]

Not truly a theory…a simplistic hypothesis at best. And I think you are right, a simple summation is probably NOT truly correct and there might be functions of functions with the variables identified (and some that were not).

Still, I have found that for every extremely complicated system, idea, notion, or what have you, there is always a higher level “dumbed down” version that is the 90% solution (or better level), and focusing on trying to achieve the 100% level might be an effort in diminishing returns.

In this case, my personal goal with the question is trying to understand (if possible), the relative contribution of making the nutritional component as efficient as possible versus the anabolic pathway. We all know the anabolic method works for most people…but I wonder if one can equal the anabolic pathway via these nutritional methods PLUS a much lower dose of anabolics.


#10

[quote]thenewguy wrote:
Also, again excuse my physiological ignorance, but does mTOR signal protein synthesis in a “binary” way(adequate mTOR -> signal protein synthesis -> build muscle, inadequate mTOR -> no protein synthesis -> no muscle built) or in a linear way(more mTOR -> greater signaling -> greater degree of muscle being built).

Also, if it is binary, is the signaling of protein synthesis edge(signal protein synthesis when I go from low to high) or level(continuously signal while high) triggered?

Please excuse all the computer analogies… :)[/quote]

Good questions!


#11

[quote]buffd_samurai wrote:

[quote]thenewguy wrote:
I, too, am a computer engineer fixated on increasing strength and muscle mass who unfortunately lacks any formal physiology background. :confused:

Hmm, very interesting theory you have, but I would imagine that mTOR wouldn’t be a simple summation, due to interplay among the variables, as well as saturation.[/quote]

Not truly a theory…a simplistic hypothesis at best. And I think you are right, a simple summation is probably NOT truly correct and there might be functions of functions with the variables identified (and some that were not).

Still, I have found that for every extremely complicated system, idea, notion, or what have you, there is always a higher level “dumbed down” version that is the 90% solution (or better level), and focusing on trying to achieve the 100% level might be an effort in diminishing returns.

In this case, my personal goal with the question is trying to understand (if possible), the relative contribution of making the nutritional component as efficient as possible versus the anabolic pathway. We all know the anabolic method works for most people…but I wonder if one can equal the anabolic pathway via these nutritional methods PLUS a much lower dose of anabolics.

[/quote]

Ahh yes, I meant hypothesis, please excuse my misuse of words.

Also apologies if it felt like I was trying to correct you in any way, mostly I was just thinking out loud. I definitely agree with the benefits of models and simplifications!


#12

Hi, I am an undergraduate Biology major and I am doing a senior research project based on dexamethasone-induced (strong synthetic cortisol) muscle atrophy in mice. I am pretty well read on glucocorticoid induced muscle atrophy.

I think you are missing out on a few things.

  1. Insulin is the most anabolic hormone in the body, I am pretty sure John Meadows wrote an article about this. Androgens help you pack on muscle without a doubt, but if you do not have a strong presence of insulin signaling peri-workout you will not gain as much muscle mass as possible. If you look up insulin’s effects on mTOR it will blow your mind.

  2. You never want to trigger gluconeogenesis if you are a serious weightlifter. Glucocorticoids scavenge the muscles for amino acids to create glucose. It causes serious muscle breakdown, the Type II Fast-Twitch non-oxidative are the first fibers to go (WHICH TOTALLY SUCKS). Glucocorticoids completely turn off the mTOR pathway. Glucocorticoids also have various effects on decreasing the formation of androgens. Moral of the story: Nutrition, Nutrition, and perfecting your Nutrition.

  3. You have to do anything you can to eliminate myostatin prduction and signaling. It is the key hormone that triggers muscle atrophy and turns of mTOR.

  4. A person must nurture their mesenchymal stem cells that sit in the muscle tissue. A lot of research is coming out describing how mesenchymal stem cells (which we once thought did not do anything) are doing a lot of chemical signaling with the muscle cells surrounding the area. I read an article about how mesenchymal stem cell proliferation increased MyoD signaling. MyoD is a hormone that deacetylates histone proteins in the DNA (I could be mistaken) which opens up large sections of DNA that have the genes mTOR signaling mechanisms actively express. There is a ton of research on MyoD, read it.

Overall, if you eliminate all muscle atrophy signaling with proper nutrition and correct amounts of rest the gains will come. Your androgen production will eventually increase if you eliminate all muscle atrophy signaling. Testosterone is pretty easy to elevate naturally anyway.

You could probably wreck me in a linear algebra or optics class, but human physiology is a completely different way of thinking. There is no equation that could possibly encapsulate the complexities of muscle cell signaling. There are hundreds of factors (I only gave 4 you probably did not consider) and scientists are just starting to discover even more complexities. Instead of formulating an equation, take the time to read some research and discover what simple habits you can add to your life to increase positive signaling networks or decrease the effects of negative signaling networks.

-Golem


#13

[quote]adamgolem wrote:
Hi, I am an undergraduate Biology major and I am doing a senior research project based on dexamethasone-induced (strong synthetic cortisol) muscle atrophy in mice. I am pretty well read on glucocorticoid induced muscle atrophy.

I think you are missing out on a few things.

  1. Insulin is the most anabolic hormone in the body, I am pretty sure John Meadows wrote an article about this. Androgens help you pack on muscle without a doubt, but if you do not have a strong presence of insulin signaling peri-workout you will not gain as much muscle mass as possible. If you look up insulin’s effects on mTOR it will blow your mind.

  2. You never want to trigger gluconeogenesis if you are a serious weightlifter. Glucocorticoids scavenge the muscles for amino acids to create glucose. It causes serious muscle breakdown, the Type II Fast-Twitch non-oxidative are the first fibers to go (WHICH TOTALLY SUCKS). Glucocorticoids completely turn off the mTOR pathway. Glucocorticoids also have various effects on decreasing the formation of androgens. Moral of the story: Nutrition, Nutrition, and perfecting your Nutrition.

  3. You have to do anything you can to eliminate myostatin prduction and signaling. It is the key hormone that triggers muscle atrophy and turns of mTOR.

  4. A person must nurture their mesenchymal stem cells that sit in the muscle tissue. A lot of research is coming out describing how mesenchymal stem cells (which we once thought did not do anything) are doing a lot of chemical signaling with the muscle cells surrounding the area. I read an article about how mesenchymal stem cell proliferation increased MyoD signaling. MyoD is a hormone that deacetylates histone proteins in the DNA (I could be mistaken) which opens up large sections of DNA that have the genes mTOR signaling mechanisms actively express. There is a ton of research on MyoD, read it.

Overall, if you eliminate all muscle atrophy signaling with proper nutrition and correct amounts of rest the gains will come. Your androgen production will eventually increase if you eliminate all muscle atrophy signaling. Testosterone is pretty easy to elevate naturally anyway.

You could probably wreck me in a linear algebra or optics class, but human physiology is a completely different way of thinking. There is no equation that could possibly encapsulate the complexities of muscle cell signaling. There are hundreds of factors (I only gave 4 you probably did not consider) and scientists are just starting to discover even more complexities. Instead of formulating an equation, take the time to read some research and discover what simple habits you can add to your life to increase positive signaling networks or decrease the effects of negative signaling networks.

-Golem[/quote]

Some interesting points you raised here. I’d be curious if you had more info specifically on points 3&4? What can you do (aside from anabolic steroids) to decrease myostatin? If anything. Also, how do you nuture mesenchymal stem cells? Thanks


#14

I apologize. I mixed up mesenchymal stem cells with Myosatellite cells. So in point 4 I was talking about Myosatellite cells.