Can your androgen receptors be saturated?

[Paperclip]

I've heard several times that there's apparently some kind of AR saturation effect phenomenon, for example, people say that DHT can act like a SERM because it competes with testosterone at the receptor site. From what I imagine, if the ARs can't be saturated this can't happen.

Can ARs really be saturated? If yes, at what amount of androgens circulating?

 

[Sworder]

Yes, the AR's can be saturated. I have seen figures around 3-4grams/week of Test to achieve this state of maximum manliness. But that figure doesn't take in consideration the sides that accompany it.

 

[benchingover500]

yes, you can have saturation & long term saturation leads to desentization.

 

[Bill Roberts]

And the resulting desensitization is why using more anabolic steroids gives less results.

Oh wait.... ?

Saturation means that essentially all the receptors are occupied and working. It isn't demonstrated that there's anything worse or less effective about DHT occupying a receptor site than testosterone.

Sworder's figure is essentially the same as my estimate The only data I've seen on it was less precise than would be desired, but was consistent with this.

 

[benchingover500]

exactly.

 

[Bill Roberts]

I wrote that poorly: by "oh wait," I meant that results are not less, from using more steroids.

 

[benchingover500]

anytime you have consistent stimulation of receptors, you get desentization where the number of receptors being expressed goes down. it's in goodman & gillman.

 

[benchingover500]

so while the ligand concentration may still be high, you get a decreased effect because there are less receptors being expressed & you don't have spare receptors in this state. it's the same as when you see decreased effect of prolonged albuterol use due to decreased b3 receptors being expressed on adipocytes thus decreased lipolysis.

 

[whitegato777]

I think they call it down regulation.

 

[dfein]

The only problem is that there is not a single scientific study which says androgen receptors downregulate in response to testosterone use. The androgen receptors are supposed to be fully saturated at the peak of natural levels. The fact is that it's far too complicated to understand what's going on. It may be that myostatin is increasing in response to high androgens in order to control the situation. There's also the issue that certain people respond to androgens better than others (Arnold), yet they cannot find any difference in androgen receptors (except the CAG repeat, but one study debunked that too).

 

[benchingover500]

in the field of pharmacology, these studies were done, but at the basic level. what I mean by this is they were not done on live animals but on cell preps, muscle strips, & cell culture. While some may doubt the applicability of the studies, most of the principles of receptor theory continue to be true.

 

[Bill Roberts]

As you clearly have an interest in the subject and have already put some substantial work into it, You may enjoy reading my article on that: Androgen Receptor Regulation by Bill Roberts

There has of course been work done since but I haven't seen anything invalidating what I've written.

Fora far shorter version: the studies you refer to show downregulation as androgen levels increase from zero up to normal.

It is true that the body responds to abnormally low androgen levels by increasing the number of androgen receptors: this effect is lost on restoring androgen levels.

That is a totally different matter than what happens when androgen levels are increased above normal.

 

[Millard]

The only problem is that there is not a single scientific study which says androgen receptors downregulate in response to testosterone use. The androgen receptors are supposed to be fully saturated at the peak of natural levels. The fact is that it's far too complicated to understand what's going on. It may be that myostatin is increasing in response to high androgens in order to control the situation. There's also the issue that certain people respond to androgens better than others (Arnold), yet they cannot find any difference in androgen receptors (except the CAG repeat, but one study debunked that too).

Do you have those CAG repeat studies?

 

[Millard]

in the field of pharmacology, these studies were done, but at the basic level. what I mean by this is they were not done on live animals but on cell preps, muscle strips, & cell culture. While some may doubt the applicability of the studies, most of the principles of receptor theory continue to be true.

MESO-Rx has published a few articles on androgen receptors:

Androgen Receptor Regulation by Bill Roberts

Androgen Action and the Androgen Receptor by John Berardi

Androgen Receptors Downregulate - Don't They? Part 1 by Bryan Haycock

Androgen Receptors Downregulate - Don't They? Part 2 by Bryan Haycock

 

[Bill Roberts]

Wow... on re-reading my article, I'm kind of shocked how badly I took apart the other author in question.

These days, and in recent years, I'd have never done that to anything like that extent. In fact I would never have selected a particular author at all.

Well, people change with time. It was surprising to see: I'd actually forgotten that I sometimes used to be THAT rough in my refutations.

But at least views in bb'ing changed. Though the downregulation theory didn't disappear entirely, it became much less frequently claimed, and when claimed, much more moderately claimed.

It actually used to be held that your first cycle damaged your androgen receptors for the rest of your life, that you'd never have the sensitivity to testosterone that you'd had before, etc.

At least that isn't being claimed any more, or if it is, not often.

 

[dfein]

If it does follow typical receptor behavior, it would mean that sensitivity would be restored after an extended period of time. It would also seem that if someone were hypogonadal, they would be to a near-normal state from the receptors upregulating, but that doesn't happen either. Since testosterone controls erections/libido, it would mean someone after a cycle would not be able to maintain an erection on normal levels of testosterone because he had desensitized his receptors. I believe it has something to do with the body trying to control the size of muscle, thus it is negating the effect of testosterone, but not testosterone itself.

Here are the CAG repeat studies:

http://msscentershop.info/content/45/2/95.abstract

Ethnic Variation in Allele Distribution of the Androgen Receptor (AR) (CAG)n Repeat -- Ackerman et al., 10.2164/jandrol.111.013391 -- Journal of Andrology

This one appears to reveal that Afro-Carribeans have the shortest CAG repeat and that Thais have the longest one. It doesn't seem to me that Thais have trouble putting on lean mass.

 

[Bill Roberts]

One really can't reason by "typical receptor behavior." Each type needs to be looked at individually.

 

[dfein]

One really can't reason by "typical receptor behavior." Each type needs to be looked at individually.

In the same token, you can't expect it to downregulate either then. I believe something does occur, but whether it's related directly to the receptor is the question. For a vital hormone to downregulate something for an extended period of time doesn't seem to actually help you. It doesn't seem like it makes sense to me that your own body will hurt itself by downregulating the receptor and allow you to not have testosterone.

I forgot this study also:

:: EnM :: Endocrinology and Metabolism

 

[BBC3]

SO if Bill is still watching these are questions and not statements:

I dont see how "saturation" could apply other than the feeling of getting used to cellular activity in muscle. I think that the concept of ACTIVITY, rather than saturation as a description of usefullness should apply. Meaning we achieve plateaus of cellular activity that are interpreted as deficiencies in action or use???

Perhaps plateaus are merely full saturations in available muscle cell activity due to inherent limitations, and the only way past them is to generate new muscle cells via stress/load induced natural GH release and stimulation of new cell growth which takes time varying upon genetic propensity in individuals.???

The muscle cells are either working properly, or they are not. Should this not be measured in functional strength and not growth rates. It stands to reason that the only way to gain new strength is to proliferate new muscle cells. Why should some failure be blamed on RECEPTORS. They are doing the same job they did the week before one claims their "juice is no longer working"???

What?? Does something change in this stated "saturation". Did muscle cells all of the sudden deflate or become inactive?? Are people attributing this phenomena to a decrease in measured strength? I always assumed it was a complaint about a wall to further increases in strength?? Why would anyone think that its just going to keep going up once present cellular activity is maxed??

It must be all genetic?? Cellular density and composition?? And the ability to grow new cells at given stages of life with corrolation to AAS supping??

Has this whole notion of "receptor saturation" been created as simply a reason to account for current geneticly inclined tissue composition, and the limitations there of?

Consider nicotine, alcohol, or narcotics. Sure receptors become saturated. But all this means is that they are fully involved. I have never seen where the substance/drug is not doing its job in full still. The only thing that appears to change is our perception of the event is no longer NEW TO US, and therefore now discounted psychologically??

4 GRAMS!!!! You of course are talking a serously trained MOFO!! I guarantee you could saturate me with about 1 gram a week. But dont you also have to consider all the derivative hormones especially with regard to estrogen to define saturation??

It would be interesting to take an individual who is supping massive amounts of testosterone and measure the different intervals in which EXCRETION increases, both changed and unchaged, given a preset administration protocal....

It just seems to me that any blames pointed toward receptors should be stated I guess more like "resistance". And this is an extremely rare condition qualified more like an illness I would speculate, rather than a possible temporary condition???/

 

[Michael Scally MD]

Antonio J, Wilson JD, George FW. Effects of castration and androgen treatment on androgen-receptor levels in rat skeletal muscles. J Appl Physiol 1999;87(6):2016-9. Effects of castration and androgen treatment on androgen-receptor levels in rat skeletal muscles

The effects of castration and dihydrotestosterone (DHT) treatment on levels of skeletal muscle androgen receptor (AR) were examined in three groups of adult male rats: 1) intact normal rats, 2) rats castrated at 16 wk of age, and 3) rats castrated at 16 wk of age and given DHT for 1 wk starting at week 17. All animals were killed at 18 wk of age.

Castration caused a decrease (P < 0.05) in the weights of the levator ani and bulbocavernosus muscles. The administration of DHT to the castrated rats increased (P < 0.05) the weights of the levator ani and bulbocavernosus muscles.

Castration caused a significant downregulation of AR levels in the bulbocavernosus (P < 0.05) but had no significant effect on AR levels in the levator ani muscle. DHT administration to the castrated group upregulated AR levels in the bulbocavernosus and levator ani muscles. The plantaris muscle did not significantly (P > 0.05) change for any of the treatments. These findings suggest that the effects of castration and androgen replacement differentially affect skeletal muscle mass and AR levels.


Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S. Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment. Journal of Clinical Endocrinology & Metabolism 2004;89(10):5245-55. Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment

Androgens stimulate myogenesis, but we do not know what cell types within human skeletal muscle express the androgen receptor (AR) protein and are the target of androgen action. Because testosterone promotes the commitment of pluripotent, mesenchymal cells into myogenic lineage, we hypothesized that AR would be expressed in mesenchymal precursor cells in the skeletal muscle. AR expression was evaluated by immunohistochemical staining, confocal immunofluorescence, and immunoelectron microscopy in sections of vastus lateralis from healthy men before and after treatment with a supraphysiological dose of testosterone enanthate. Satellite cell cultures from human skeletal muscle were also tested for AR expression.

AR protein was expressed predominantly in satellite cells, identified by their location outside sarcolemma and inside basal lamina, and by CD34 and C-met staining. Many myonuclei in muscle fibers also demonstrated AR immunostaining. Additionally, CD34+ stem cells in the interstitium, fibroblasts, and mast cells expressed AR immunoreactivity. AR expression was also observed in vascular endothelial and smooth muscle cells. Immunoelectron microscopy revealed aggregation of immunogold particles in nucleoli of satellite cells and myonuclei; testosterone treatment increased nucleolar AR density. In enriched cultures of human satellite cells, more than 95% of cells stained for CD34 and C-met, confirming their identity as satellite cells, and expressed AR protein. AR mRNA and protein expression in satellite cell cultures was confirmed by RT-PCR, reverse transcription and real-time PCR, sequencing of RT-PCR product, and Western blot analysis.

Incubation of satellite cell cultures with supraphysiological testosterone and dihydrotestosterone concentrations (100 nm testosterone and 30 nm dihydrotestosterone) modestly increased AR protein levels. We conclude that AR is expressed in several cell types in human skeletal muscle, including satellite cells, fibroblasts, CD34+ precursor cells, vascular endothelial, smooth muscle cells, and mast cells. Satellite cells are the predominant site of AR expression.

These observations support the hypothesis that androgens increase muscle mass in part by acting on several cell types to regulate the differentiation of mesenchymal precursor cells in the skeletal muscle.


Carson JA, Lee WJ, McClung J, Hand GA. Steroid receptor concentration in aged rat hindlimb muscle: effect of anabolic steroid administration. Journal of Applied Physiology 2002;93(1):242-50. Steroid receptor concentration in aged rat hindlimb muscle: effect of anabolic steroid administration

Skeletal muscle is a target of anabolic steroid action; however, anabolic steroid's affect on aged skeletal muscle is not well understood. The effect of 4 wk of nandrolone decanoate (ND) administration on hindlimb muscles of 5- and 25-mo-old Fischer 344/Brown Norway rats was examined. ND (6 mg/kg body wt) was injected every 7th day for 4 wk. Controls received an oil injection. ND significantly reduced 25-mo-old rat perirenal fat pad mass by 30%. Soleus (Sol) and plantaris (Plan) muscle-to-body weight ratios were reduced in 25-mo-old rats. ND did not affect Sol or Plan muscle-to-body weight ratios at either age. Sol DNA concentration was reduced by 25% in 25-mo-old rats, and ND increased it to 12% greater than 5-mo-old rats. ND did not affect Plan DNA content. Sol androgen receptor (AR) protein in 25-mo-old rats was reduced to 35% of 5-mo-old values. ND increased AR protein by 900% in 25-mo-old rat Sol. Plan AR concentration was not affected by aging but was induced by ND in both age groups. Aging or ND treatment did not affect glucocorticoid receptor levels in either muscle. These data demonstrate that fast- and slow-twitch rat hindlimb muscles differ in their response to aging and ND therapy.