Receptors explained in layman terms

[ryanbCXG]

You are asking questions that are beyond me, and even the ones that do know are probably operating on theory and conjecture to some extent. There are many steps between a hormone binding to receptor and transcription. It is fairly well known however that receptor up-regulation results in a lower sensitivity to a given amount of drug, this goes beyond just AAS and hormones.

Thanks Kal. I will have to keep my eye out for new info. I love our ever expanding view of the body. It's so complicated it will keep us busy for a long time

 

[emeric delczeg]

The fact is, excessive androgen levels induce the rapid loss of muscle testosterone receptors. The muscle fights the excess and immunizes itself against androgens, which is the reason steroids become less potent as time goes by.

 

[emeric delczeg]

The key point to remember is, only the trained muscles get bigger. The growth is determined by the numerous local alterations caused by muscular contractions, not a systemic circulating factor.

 

[warmouth]

The fact is, excessive androgen levels induce the rapid loss of muscle testosterone receptors. The muscle fights the excess and immunizes itself against androgens, which is the reason steroids become less potent as time goes by.

Thank you very much. I never understand the scientific talk too well and this helps a lot!

 

[invain]

The fact is, excessive androgen levels induce the rapid loss of muscle testosterone receptors. The muscle fights the excess and immunizes itself against androgens, which is the reason steroids become less potent as time goes by.

There is literally no scientific evidence that androgen receptor down-regulation occurs. The 'truth' is that the opposite occurs.

 

[VOXpol]

Thanks for the time writing this up.

So to understand its the proportion or percentage of receptors occupied that creates anabolism? I can't wrap my head around why even though the same number of receptors are occupied and thus binding to DNA and causing the signaling pathways activation that the results would slow as more AR are presnt even though more aren't bound until dose goes up. Hopefully I worded this so you understand.

The way he stated it is misleading. While in a practical, "diminished return" sense this explanation works, because you could say that you get less anabolism per receptor. However, it is difficult to imagine a way in which the ratio of unbound to bound androgen receptors could be what is important in causing anabolic effect. It is only the receptor-androgen complex that gets transported into the nucleus, binds to effector sites on the genome and causes the increase in protein synthesis and host other effects that we are after. The fact is that it is not known what causes the diminishing returns from steroid use. SHBP certainly plays a role. There are chaperone proteins that are involved in the process of binding and transport of the complex. It could be that the regulation that is happening is going on at the RNA and/or protein level and has nothing directly to do with androgen binding or transcription at all. I read a recent paper that showed the cellular location of androgen receptors was effected by testosterone level: this could have some affect. We just don't know, and likely won't any time soon. There isn't any compelling clinical reason for research to be done to determine why androgens lose effectiveness at the abusive doses that bodybuilders use.

The fact is, excessive androgen levels induce the rapid loss of muscle testosterone receptors.

This is the exact opposite of everything I've ever read. Specifically muscle tissue? Can you point us toward literature? I'd sincerely like to read it if there is some

 

[Kaladryn]

The way he stated it is misleading. While in a practical, "diminished return" sense this explanation works, because you could say that you get less anabolism per receptor. However, it is difficult to imagine a way in which the ratio of unbound to bound androgen receptors could be what is important in causing anabolic effect. It is only the receptor-androgen complex that gets transported into the nucleus, binds to effector sites on the genome and causes the increase in protein synthesis and host other effects that we are after.

I agree with you to some extent, but it's hard to imagine a way in which the ratio of unbound to bound androgen receptors could NOT be important in causing an anabloic effect. A 300lb bodybuilder is going to require a LOT more transcription going on just to maintain then a 200lb bodybuilder, remember everything is always in flux, catabolism is always battling anabolism.

There are many more in depth theories that hold weight also. Dan Duchain's theory was that only after all receptors are filled do androgens start becoming strong glucocorticoid receptor antagonists. Under this hypothesis, more receptors would mean more hormone is required to create enough "excess" for GC antagonism.

There are other interesting questions also, such as how much of a role the exact structure of the hormone affects the end result of transcription, since the entire complex (hormone+receptor) is part of the reaction.

How sex hormones access the AR is also any area unknown. The passive diffusion across the cell membrane theory is not longer considered the main way hormones enter the cell, it is now known that there is a membrane receptor for the SHBG complex (with hormone attached), and that entire complex is transported to the AR. Not only that, the SHBG complex has a role in modifying the resulting transcription! So what was once thought of as a storage mechanism for sex hormones is actually an active transport system.

I give these examples to further show how little of the entire process we understand, and how much more complex it is than just androgen+receptor.

 

[standard donkey]

I agree with you to some extent, but it's hard to imagine a way in which the ratio of unbound to bound androgen receptors could NOT be important in causing an anabloic effect. A 300lb bodybuilder is going to require a LOT more transcription going on just to maintain then a 200lb bodybuilder, remember everything is always in flux, catabolism is always battling anabolism.

There are many more in depth theories that hold weight also. Dan Duchain's theory was that only after all receptors are filled do androgens start becoming strong glucocorticoid receptor antagonists. Under this hypothesis, more receptors would mean more hormone is required to create enough "excess" for GC antagonism.

There are other interesting questions also, such as how much of a role the exact structure of the hormone affects the end result of transcription, since the entire complex (hormone+receptor) is part of the reaction.

How sex hormones access the AR is also any area unknown. The passive diffusion across the cell membrane theory is not longer considered the main way hormones enter the cell, it is now known that there is a membrane receptor for the SHBG complex (with hormone attached), and that entire complex is transported to the AR. Not only that, the SHBG complex has a role in modifying the resulting transcription! So what was once thought of as a storage mechanism for sex hormones is actually an active transport system.

I give these examples to further show how little of the entire process we understand, and how much more complex it is than just androgen+receptor.

interesting.. so given what you know, how would you cycle?

 

[VOXpol]

I agree with you to some extent, but it's hard to imagine a way in which the ratio of unbound to bound androgen receptors could NOT be important in causing an anabloic effect. A 300lb bodybuilder is going to require a LOT more transcription going on just to maintain then a 200lb bodybuilder, remember everything is always in flux, catabolism is always battling anabolism.

True, but (in regards to just the receptor mediated actions) this would be a function of the total amount of bound receptor-androgen complexes. Not sure how the unbound receptors would be diminishing the effect...maybe competing for limited amounts of other proteins that are involved? Not saying it's impossible by any means, I've just never seen anything pointing to the ratio specifically being important. But my research is far from exhaustive I'm definitely no expert, thats for sure

 

[Kaladryn]

interesting.. so given what you know, how would you cycle?

I would do TRT at physiological levels to maximize sensitivity between blasts.
Then I would use the least amount needed to grow, so that I could keep slowing increasing that amount for time longest time and keep growth going. If you don't plan it like this, you will initially get good gains, but you will rapidly reach the upper limit of how much you are willing to do (everyone has a limit, for one reason or another), and growth will stop soon after.

True, but (in regards to just the receptor mediated actions) this would be a function of the total amount of bound receptor-androgen complexes. Not sure how the unbound receptors would be diminishing the effect...maybe competing for limited amounts of other proteins that are involved? Not saying it's impossible by any means, I've just never seen anything pointing to the ratio specifically being important. But my research is far from exhaustive I'm definitely no expert, thats for sure

We could probably get the foremost organic chemist/molecular biologist in the world on this subject in here and he'd teach us a few cool things but most of this would still be a mystery to him also.

I don't necessarily believe that receptor proliferation is directly connected to decreased sensitivity to AAS, but it is a plausible theory presented by people smarter than myself.

 

[standard donkey]

I would do TRT at physiological levels to maximize sensitivity between blasts.
Then I would use the least amount needed to grow, so that I could keep slowing increasing that amount for time longest time and keep growth going. If you don't plan it like this, you will initially get good gains, but you will rapidly reach the upper limit of how much you are willing to do (everyone has a limit, for one reason or another), and growth will stop soon after.



We could probably get the foremost organic chemist/molecular biologist in the world on this subject in here and he'd teach us a few cool things but most of this would still be a mystery to him also.

I don't necessarily believe that receptor proliferation is directly connected to decreased sensitivity to AAS, but it is a plausible theory presented by people smarter than myself.

how long would you cruise for?

 

[D_trip]

how long would you cruise for?

Kaladryn:
And: How long does it take for you to up the dose, for continues gains?

Example:

Hrt to sensitize, then 500mg/wk for 4 weeks, 750mg for 4 weeks etc.
What perioids generally works for you and how much do you bump it when gains stall?

 

[Stewie]

I believe Patrick Arnold stated it best years ago.


Androgen Receptor Cleaner? - Page 2 - Bodybuilding.com Forums

there are hundreds of different things that regulate the anabolic response to AAS. Why everyone focuses just on the receptor I dunno. The receptor binding and translocation is step one in a huge cascade of events. Interupt any one step and you screw up the muscle growth.

I would suspect this statement is coherent too Emerics statement.

Steroid users eventually reach a point where there is a rate limiting step for muscle growth which is not related to the amount of steroid and/or the amount of receptors or even the overall androgen gene expression itself. Perhaps this step can be addressed by the use of other pharmaceutical agents, or maybe through dietary interventions. Perhaps different training protocols can help. Or maybe yer just fukked

well androgen receptors have, in addition to the site where the steroid binds, a site where the activated receptor binds to the steroid response element of the dna and also sites where "co-modulators" can bind


comodulators can be either positive (co-activators) or negative (co-repressors) regulatory compounds. in other words they can either amplify or suppress the transcriptional activity that is switched on by the AR complex

it is possible that extended usage of androgens creates an imbalance in the comodulators which results in a dampening of the transcriptional signals.

 

[Kaladryn]

I believe Patrick Arnold stated it best years ago.


Androgen Receptor Cleaner? - Page 2 - Bodybuilding.com Forums

there are hundreds of different things that regulate the anabolic response to AAS. Why everyone focuses just on the receptor I dunno. The receptor binding and translocation is step one in a huge cascade of events. Interupt any one step and you screw up the muscle growth.

I would suspect this statement is coherent too Emerics statement.

Steroid users eventually reach a point where there is a rate limiting step for muscle growth which is not related to the amount of steroid and/or the amount of receptors or even the overall androgen gene expression itself. Perhaps this step can be addressed by the use of other pharmaceutical agents, or maybe through dietary interventions. Perhaps different training protocols can help. Or maybe yer just fukked

well androgen receptors have, in addition to the site where the steroid binds, a site where the activated receptor binds to the steroid response element of the dna and also sites where "co-modulators" can bind


comodulators can be either positive (co-activators) or negative (co-repressors) regulatory compounds. in other words they can either amplify or suppress the transcriptional activity that is switched on by the AR complex

it is possible that extended usage of androgens creates an imbalance in the comodulators which results in a dampening of the transcriptional signals.

Awesome, I thought I remembered PA weighing in heavily on this subject. Co-binding factors are HUGE and relatively unknown. This is why Estradiol and Androgens compete, the AR and the ER use the same co-binding factors (SHBG may play a role as well).

 

[Kaladryn]

how long would you cruise for?

Kaladryn:
And: How long does it take for you to up the dose, for continues gains?

Example:

Hrt to sensitize, then 500mg/wk for 4 weeks, 750mg for 4 weeks etc.
What perioids generally works for you and how much do you bump it when gains stall?

These are individual questions you are better off discovering and deciding for yourself through trial and error. I will say this though, up the dose BEFORE gains stall, but not too early. If you wait until gains stall, you waited too long.

 

[BigNJ]

Fuck, no need to complicate things.

Just shoot the damn thing, eat, train.

You gain more weight, eat more, shoot a bit more, train heavier.

Take a break when you need it and get back and do it all over again.

 

[desibaba]

Fuck, no need to complicate things.

Just shoot the damn thing, eat, train.

You gain more weight, eat more, shoot a bit more, train heavier.

Take a break when you need it and get back and do it all over again.

Probably the best post in this entire thread.

 

[Zoobster]

Where can you find BMR 10?

So what about people that blast and cruise? Do your receptors clean out while your cruising.

 

[Johnny Smiles]

I have juiced for a year and never worked out that whole year and was big and lean. I certainly believe steroids and gh and slin build muscle/keep unnatural levels of muscle in the absence of work outs. add workouts and proper eating.... its kinda simple..... fairly easy....
just sayin.
-JS

 

[Aikman56]

And amidst all, this discussion, the OP is nowhere to be found...


Great info in here, guys. Thanks!:headbang: