Just wondering if it's true that receptors get flooded?

[marx]

Trevor L. Smith (dood obviously is nervous about DNP, LOL), added to fire up conversation:

A lot has been said in regards to clearing the receptors and I thought now would be a good time to delve into this subject and simplify things.

Basically, one must view the receptor sites as parking spaces.

Envision a slew of parking spaces that are all empty. Now we are going to call these parking spaces your receptor sites and we shall call steroids the cars. Now I want you to imagine one of those old 1950′s style drive up hamburger stands where the girls come up in roller skates and take your order. Typically one would order a burger, fries and a coke–ah the food of the gods–the waitress would take the order, go bring the information to the cook, who would in-turn make the food and the waitress would then bring the food to you and you would then begin eating which is the whole reason you came to the hamburger stand in the first place.

I think everyone can easily understand that. Which means everyone can easily understand all they need to know about the receptor sites because they do the exact same thing. We will keep with this hamburger stand model and explain what happens when you inject steroids

Remember how I said steroids were like the cars and the parking spaces were like the receptor sites? Well it is basically that simple. When you inject testosterone or any one of it’s anabolic or androgenic derivatives, you are sending a whole slew of “cars” into your system. Now these “cars” are on a mission–just like you would be if you were hungry and heading to a hamburger stand. They have orders to place with the cells, but before they can place them they must first find a parking space.

Now let’s say you have never used steroids before. If this were the case, it would be very much like a hamburger stand that was having a grand opening….lots and lots of empty parking spaces waiting for cars to fill them up and place their orders. The steroids (cars) enter the system and come to a brand new hamburger stand called your cells. Now these cells have never previously been open to the boat-load of anabolics that are now present in the system because they previously only dealt with what your body naturally produced. However, there are lots of extra parking spaces that can be utilized and so the steroids park themselves into these spaces.

Once they are parked a “waitress” called CYCLICl AMP literally crosses the cellular membrane which is totally impenetrably to anything else and takes the order from the steroid. The order is quite simple: Build More Muscle!!

The “waitress” then crosses back through the cellular membrane and brings the order to the “cook” called the Nucleus who begins to fill it by ordering its helpers called Ribosomes to produce muscle protein.. Now different steroids will have slightly different orders in that some may have a bigger order for the cook to fill–such as testosterone. The thing you have to realize is that a lot of times, after the order is placed, the steroid does not necessarily leave the parking space and make it available to other steroids…..it will often sit in the parking space even though it is no longer sending orders to the “waitress” to bring to the “cook”, and this is where the problem of “DOWN-REGULATION” comes in. You see even if you send in more and more fresh new “cars” to occupy the receptor spaces, if they are already taken up by old “dead cars” you are shit out of luck…..

This is why you do not continually grow by injecting bigger and bigger doses of steroids. THERE ARE A LIMITED NUMBER OF PARKING SPACES. Now it would not be so bad if all the parking spaces were taken by “cars” that were sending orders to the cook, because that is when you grow. The problem is when there are “cars” that are no longer sending orders and on top of that have dead batteries which is preventing them from exiting the receptors parking space.

This is what the whole point of this article is….TOWING AWAY ALL THE DEAD “CARS” FROM THE RECEPTOR SITES PARKING SPACES AS TO FREE THEM UP FOR NEW, FRESH, HUNGRY “CARS” TO OCCUPY THEM…This will result in new muscle mass!

O.K. Trevor, I am with you so far, but what the f*** can I do about it?

The answer is …PLENTY!

First and foremost, is to plan sensible courses. This is why I am an advocate of short courses designed in such a fashion as to have all drugs out of the system by the end of the cycle and then allow for a 3-4 week off time in which you are totally clean. If you stay on these monster 4-6 month courses, you just wind up screwing yourself and requiring that much longer of an off period. The longer you are on, the more the body recognizes that there is “too much” in the system and will begin to take counter measures. And the longer you are on, the more “dead cars” you will have sitting in the receptor parking spaces which means NO MORE GROWING!

Now with this in mind, how can we help get the cars out of there?

Well WE actually cannot, but the body can and will. Basically as time goes by, the body will free up the parking spaces just like a tow truck would remove a dead car from a parking space. However, you are at the mercy of time in this situation which is why it is important to utilize short courses that will cause less disturbance in the system, less “dead cars” in the receptor spaces and therefore less time needed for the body to remove them and free up the spaces.

That being said, it should be noted that even short course will pile up “dead cars” after a while and you should give yourself an extended clean out of 2 months at least once a year.

But Trevor, isn’t there anything I can do to help speed the process?

Once again the answer is yes!

You can help speed the process up dramatically by increasing your metabolic rate…Speeding up the metabolic rate is akin to hiring extra tow trucks to clear out all those “dead cars” that are occupying the receptor sites!

Have you ever know a person who was much, much fatter than you and yet ate half as much?

These poor bastards think they were given the genetic shaft and try every diet fad imaginable only to stay fat. Their problem no longer lies in their eating habits–which is ironic–; it lies in their metabolism, which basically was shut down due to the excess eating and lack of exercise that got them fat in the first place. Once you understand this, you can easily control your weight for the rest of your life. But what the f*** does this have to due with steroid receptor sites?

EVERYTHING!

The same thing I would prescribe someone whose metabolism has shut down due to obesity, is the same thing I would prescribe someone who’s receptor sites are all clogged and is no longer making progress….INCREASE THE METABOLIC RATE!!

Below I will outline a few ways this can be achieved in the constraints of a 4 week Receptor Clearing Cycle follwing the completion of a Muscle Building Course using anabolics:

Diet: I suggest cutting back 300 calories below maintenance per day during a 4 week off time from your anabolic regime…I also suggest eating 6-8 small meals spread out from early morning to late at night. The higher the number of meals you eat, the more your body has to go to work and break down the food which causes the metabolic rate to increase.

Aerobics: Yet another tool in the battle to increase the metabolism, I would suggest low level aerobics 5 times per week 30 minutes per session.

Pharmacology: It is important that one does not have ANY anabolics that are active in the system during this time period…..make sure that you have had a good 4 weeks since your last shot of long acting compound before you embark on this 4 week receptor clearing cycle….otherwise you are wasting your ****ing time! That being said, I would suggest the use of the following compounds to help accelerate the Receptor Clearing Process:

1. D.N.P.– Understand that this is a ****ing vicious poison and a component in T.N.T., and I do not suggest it’s use at all, but to be fair I must admit that NOTHING can raise the metabolic rate like D.N.P. can. Because this is well known, there are many people that will want to try it…This being the case, D.N.P. should only be used in the following manner during this course: 3 days on, 4 days off at a dose of 4mg per kilogram of bodyweight taken before bed—-have plenty of towels around and a fan to keep you cool!

2. Cytomel–T3 is another booster of metabolic rate which is why the fitness models live on this stuff…it keeps you engines running high and burns the fat right off….In this case, we are more concerned with the fact that it increases the metabolic rate. Suggested use is 75mcg -100mcg 5 days on 2 days off for the 4 week course

Clen– is also another good option to help accelerate the Receptor Clearing Process seeing it boosts the metabolic rate also.

* If you do not wish to use D.N.P.—which I think is the smarter approach as it is very dangerous.

There you have it…a brief simple lesson on your receptors and how you might go about keeping them free and clear so you can continue to Grow, Grow, Grow and they begin to go to work.

 

[marx]

Brian Haycock wrote an interesting 2 part piece about "downregulation":

Androgen Receptors Downregulate Don’t They? Part 1 & 2

Part 1

There is as much misinformation about steroids as there is good information had among bodybuilding enthusiasts. Go to any gym and you will hear some kid spouting off to his buddies about how steroids do this, or how they do that, or whatever. This soon starts somewhat of a pissing contest (excuse the expression) as to who knows more about steroids. It’s the same kind of titillating and infectious banter that adolescent boys get into about girls and sex. With steroid banter you hear all the popular terms like Deca, Test, GH, gyno, zits, raisins, “h-u-u-u-ge”, roid, freak, monster, roid-rage, “I knew this guy once”, etc., etc.. If by some rare chance they are smart and have been reading this or some other high quality bodybuilding site on the net, they may actually get a few details right. More often than not they know just enough to be dangerous. Fortunately steroids haven’t proven to be all that dangerous. Not only that, but most of these guys who are infatuated with steroids won’t ever use or even see them except in magazines.
This kind of ego driven gym talk doesn’t really bother me until they begin giving advice to other clueless people who actually have access to them. Spewing out steroid lingo gives other less experienced kids the impression that these kids actually know what they are talking about. That’s how all of the psuedo-science folklore about steroids perpetuates. This is also why most people who actually use steroids know little about them. This last fact should bother anyone who cares about bodybuilding and/or bodybuilders.

I started out with this article planning on giving some textbook style explanation as to why using steroids doesn’t down regulate androgen receptors (AR). Then after considering some of my critics views that I tend to write articles that hardly anyone can read, I decided to write an easy to read, yet informative explanation about what androgens actually do and how this precludes androgen receptor down regulation. I still have a few references but not so many that it looks like a review paper.

Androgen receptors down-regulate….Don’t they?

One misunderstood principle of steroid physiology is the concept of androgen receptors (AR), sometimes called “steroid receptors”, and the effects of steroid use on their regulation. It is commonly believed that taking androgens for extended periods of time will lead to what is called AR “down regulation”. The premise for this argument is; when using steroids during an extended cycle, you eventually stop growing even though the dose has not decreased. This belief has persisted despite the fact that there is no scientific evidence to date that shows that increased levels of androgens down regulates the androgen receptor in muscle tissue.

The argument for AR down-regulation sounds pretty straightforward on the surface. After all, we know that receptor down-regulation happens with other messenger-mediated systems in the body such as adrenergic receptors. It has been shown that when taking a beta agonist such as Clenbuterol, the number of beta-receptors on target cells begins to decrease. (This is due to a decrease in the half-life of receptor proteins without a decrease in the rate that the cell is making new receptors.) This leads to a decrease in the potency of a given dose. Subsequently, with fewer receptors you get a smaller, or diminished, physiological response. This is a natural way for your body to maintain equilibrium in the face of an unusually high level of beta-agonism.
In reality this example using Clenbuterol is not an appropriate one. Androgen receptors and adrenergic receptors are quite different. Nevertheless, this is the argument for androgen receptor down-regulation and the reasoning behind it. The differences in the regulation of ARs and adrenergic receptors in part show the error in the view that AR down-regulate when you take steroids. Where adrenergic receptor half-life is decreased in most target cells with increased catecholamines, AR receptors half-live’s are actually increased in many tissues in the presence of androgens.1
Let me present a different argument against AR down-regulation in muscle tissue. I feel that once you consider all of the effects of testosterone on muscle cells you come to realize that when you eventually stop growing (or grow more slowly) it is not because there is a reduction in the number of androgen receptors.

Testosterone: A multifaceted anabolic

Consider the question, “How do anabolic steroids produce muscle growth?” If you were to ask the average bodybuilding enthusiast I think you would hear, “steroids increase protein synthesis.” This is true, however there is more to it than simple increases in protein synthesis. In fact, the answer to the question of how steroids work must include virtually every mechanism involved in skeletal muscle hypertrophy. These mechanisms include:
· Enhanced protein synthesis
· Enhanced growth factor activity (e.g. GH, IGF-1, etc.)
· Enhanced activation of myogenic stem cells (i.e. satellite cells)
· Enhanced myonuclear number (to maintain nuclear to cytoplasmic ratio)
· New myofiber formation

Starting with enhanced growth factor activity, we know that testosterone increases GH and IGF-1 levels. In a study by Fryburg the effects of testosterone and stanozolol were compared for their effects on stimulating GH release.2 Testosterone enanthate (only 3 mg per kg per week) increased GH levels by 22% and IGF-1 levels by 21% whereas oral stanozolol (0.1mg per kg per day) had no effect whatsoever on GH or IGF-1 levels. This study was only 2-3 weeks long, and although stanozolol did not effect GH or IGF-1 levels, it had a similar effect on urinary nitrogen levels.
What does this difference in the effects of testosterone and stanozolol mean? It means that stanozolol may increase protein synthesis by binding to AR receptors in existing myonuclei, however, because it does not increase growth factor levels it is much less effective at activating satellite cells and therefore may not increase satellite cell activity nor myonuclear number directly when compared to testosterone esters. I will explain the importance of increasing myonuclear number in a moment, first lets look at how increases in GH and IGF-1 subsequent to testosterone use effects satellite cells…
In part 2 we will discuss the role of satellite cells and myonuclei and how testosterone (androgens) activates these systems to create muscle growth far beyond what simple activation of the androgen receptor can produce.

 

[marx]

Androgen Receptors Downregulate Don’t They? Part 2

In part 1 of this article we discussed the mistake of thinking about androgen receptors (testosterone receptors) in the same way we think of other receptors such as beta-receptors. Beta-receptors down regulate in response to beta-adrenergic stimulation whereas there is good evidence that androgen receptors increase in numbers in response to androgens. We also discussed the various affects of testosterone on muscle growth. Testosterone does far more than simply increase the rate of protein synthesis!

Now in part 2 we will finish our discussion of androgen receptor regulation as it pertains to the way muscle cells grow. The very mechanism of real muscle growth opens the door for increased androgen receptor number in response to testosterone treatment.

Don’t forget Satellite cells!

Satellite cells are myogenic stem cells, or pre-muscle cells, that serve to assist regeneration of adult skeletal muscle. Following proliferation (reproduction) and subsequent differentiation (to become a specific type of cell), satellite cells will fuse with one another or with the adjacent damaged muscle fiber, thereby increasing the number of myonuclei for fiber growth and repair. Proliferation of satellite cells is necessary in order to meet the needs of thousands of muscle cells all potentially requiring additional nuclei. Differentiation is necessary in order for the new nucleus to behave as a nucleus of muscle origin. The number of myonuclei directly determines the capacity of a muscle cell to manufacture proteins, including androgen receptors.

In order to better understand what is physically happening between satellite cells and muscle cells, try to picture 2 oil droplets floating on water. The two droplets represent a muscle cell and a satellite cell. Because the lipid bilayer of cells are hydrophobic just like common oil droplets, when brought into proximity to one another in an aqueous environment, they will come into contact for a moment and then fuse together to form one larger oil droplet. Now whatever was dissolved within one droplet (i.e. nuclei) will then mix with the contents of the other droplet. This is a simplified model of how satellite cells donate nuclei, and thus protein-synthesizing capacity, to existing muscle cells.

Enhanced activation of satellite cells by testosterone requires IGF-1. Those androgens that aromatize are effective at not only increasing IGF-1 levels but also the sensitivity of satellite cells to growth factors.3 This action has no direct effect on protein synthesis, but it does lead to a greater capacity for protein synthesis by increasing fusion of satellite cells to existing fibers. This increases the number of myonuclei and therefore the capacity of the cell to produce proteins. That is why large bodybuilders will benefit significantly more from high levels of androgens compared to a relatively new user.
Testosterone would be much less effective if it were not able to increase myonucleation. There is finite limit placed on the cytoplasmic/nuclear ratio, or the size of a muscle cell in relation to the number of nuclei it contains.4 Whenever a muscle grows in response to training there is a coordinated increase in the number of myonuclei and the increase in fiber cross sectional area (CSA). When satellite cells are prohibited from donating viable nuclei, overloaded muscle will not grow.5,6 Clearly, satellite cell activity is a required step, or prerequisite, in compensatory muscle hypertrophy, for without it, a muscle simply cannot significantly increase total protein content or CSA.

More myonuclei mean more receptors

So it is not only true that testosterone increases protein synthesis by activating genetic expression, it also increases the capacity of the muscle to grow in the future by leading to the accumulation of myonuclei which are required for protein synthesis. There is good reason to believe that testosterone in high enough doses may even encourage new fiber formation. To quote the authors of a recent study on the effects of steroids on muscle cells:
“Intake of anabolic steroids and strength-training induce an increase in muscle size by both hypertrophy and the formation of new muscle fibers. We propose that activation of satellite cells is a key process and is enhanced by the steroid use.”7

Simply stated, supraphysiological levels of testosterone give rise to increased numbers of myonuclei and thereby an increase in the number of total androgen receptors per muscle fiber. Keep in mind that I am referring to testosterone and testosterone esters. Not the neutered designer androgens that people take to avoid side effects.'

Another group of researchers are quoted as saying:

“…it is intriguing to speculate that the upregulation of AR levels via the administration of pharmacological amounts of androgens might convert some muscles that normally have a minor or no response to muscles with enhanced androgen responsiveness”(8)

This is not an argument to rapidly increase the dosages you use. It takes time for these changes to occur and the benefits of higher testosterone levels will not be immediately realized. It does shed some light however on the proportional differences between natural and androgen assisted bodybuilders physiques.

Maintenance of the kind of muscle mass seen in top-level bodybuilders today requires a given level of androgens in the body. That level will vary from individual to individual depending on their genetics. Nevertheless, if the androgen level drops, or if they were to “cycle off” the absolute level of lean mass will also drop. Likewise, as the level of androgens goes up, so will the level of lean mass that individual will be able to maintain. All of this happens without any evidence of AR down regulation. More accurately it demonstrates a relationship between the amount of androgens in the blood stream and the amount of lean mass that you can maintain. This does not mean that all you need is massive doses to get huge. Recruitment of satellite cells and increased myonucleation requires consistent “effective” training, massive amounts of food, and most importantly, time. Start out with reasonable doses.

Then, as you get bigger you can adjust your doses upwards.

References:
1. Kemppainen JA, Lane MV, Sar M, Wilson EM. Androgen receptor phosphorylation, turnover, nuclear transport, and transcriptional activation. Specificity for steroids and antihormones. J Biol Chem 1992 Jan 15;267(2):968-74
2. Fryburg DA., Weltman A., Jahn LA., et al: Short-term modulation of the androgen milieu alters pulsatile, but not exercise- or growth hormone releasing hormone-stimulated GH secretion in healthy men: Impact of gonadal steroid and GH secretory changes on metabolic outcomes. J Clin Endocrinol. Metab. 82(11):3710-37-19, 1997
3. Thompson SH., Boxhorn LK., Kong W., and Allen RE. Trenbolone alters the responsiveness of skeletal muscle satellite cells to fibroblast growth factor and insulin-like growth factor-I. Endocrinology. 124:2110-2117, 1989
4. Rosenblatt JD, Yong D, Parry DJ., Satellite cell activity is required for hypertrophy of overloaded adult rat muscle. Muscle Nerve 17:608-613, 1994
5. Rosenblatt JD, Parry DJ., Gamma irradiation prevents compensatory hypertrophy of overloaded extensor digitorum longus muscle. J. Appl. Physiol. 73:2538-2543, 1992
6. Phelan JN, Gonyea WJ. Effect of radiation on satellite cell activity and protein expression in overloaded mammalian skeletal muscle. Anat. Rec. 247:179-188, 1997
7. Kadi F, Eriksson A, Holmner S, Thornell LE. Effects of anabolic steroids on the muscle cells of strength-trained athletes. Med Sci Sports Exerc 1999 Nov;31(11):1528-34
8. Antonio J, Wilson JD, George FW. Effects of castration and androgen treatment on androgen-receptor levels in rat skeletal muscles. J Appl Physiol. 1999 Dec;87(6):2016-9

 

[GiantSlayer]

Iduno, I'm still on the fence.