If you consider yourself an educated bodybuilder – this is information you should know. This is also information you would likely need to explain to your friends, because I wager most of it would be alien to them. If you are a newbie, I didn't author this piece with you in mind. This is not basic information, nor is it for the basic bodybuilder.
Don't be basic. Don't be a meat-head. Don't be a cliche.
Muscle is power, knowledge is power. Have BOTH.
The Androgen receptor is a nuclear type of receptor. That means, when the Androgen receptor binds its ligand (=activator molecule), e.g. Testosterone, the receptor turns to its activated confirmation (=molecular shape); In it's activated form, it engages with the DNA inside the cell, and causes the synthesis of effector proteins that cause the biological effects. When the ligand dissociates, or unbinds from the Androgen receptor, it goes back to its inactive confirmation, disengages the DNA, and the effector proteins will no longer be synthesized.
The overwhelming majority of receptors in the human body, have a baseline activity. That means that given the total number of receptors in the human body, a fraction would be active, while a fraction would be inactive at any point in time. This is determined by the concentration of the ligand, in this case – Testosterone, in the circulation.
This means, that taking exogenous Testosterone causes an increase in free Testosterone concentration, which causes a greater fraction of the Androgen receptors to be bound and rendered active. Once the free Testosterone concentration decreases (i.e. You stop taking exogenous Testosterone) a fraction of the Androgen receptors would go back to their inactive state.
This is where you get a lot of stupid statements made. The cells do not classically increase or decrease the number of Androgen receptors. There is a set amount. The effects mediated by these receptors are exclusively due to the ratio of active to inactive receptors. This is regulated by the concentration of the ligand (e.g. Testosterone).
That also means that above a certain amount of exogenous Testosterone – any additional amount wouldn't have an additional effect, since receptors have achieved saturation. In this case – more Testosterone doesn't mean more effect, but it may indeed result in more side effects.
The Androgen receptor is a protein that ages. As some receptors age and stop working, they are degraded while other are made. Receptors are degraded and synthesized at the same rate - that keeps the total number of receptors stable within the cell. You cannot “make” more Androgen receptors nor can you “clear” your Androgen receptors any more than you can “clear” all of your red blood cells and replace them with brand new ones.
The number of Androgen receptors any one person has in a cell is genetically pre-determined. That also explains why certain individuals will be much more responsive to steroids than others. Genetics is everything when it comes to the quantity and responsiveness of your receptors.
You cannot affect the number or "maintain" your Androgen receptors, but you CAN reduce their potency, affinity, and potentially maximal number of receptors per cell if you expose yourself to high amounts of exogenous Testosterone before the age of 22-25.
One more variable of receptor activation is dictated by a term called ligand affinity. That means that some ligands (=activator molecules) once bound stay bound for a much longer period of time, while others stay bound for a lesser period of time. If Trenbolone, for example, activates an Androgen receptor and stays bound for an extended period of time, that Androgen receptor would remain active continually causing biological effects without a pause.
That also explains why you cannot replicate a high dose of Trenbolone with a super duper high dose of Testosterone. Simply because even if you have overwhelming concentration of Testosterone, you wouldn't be able to change the fact that at any given time some of these ligands would “jump off” the receptor, which would be rendered inactive until the next ligand "jumps on" to activate it.
SARMs activate the Androgen receptor in the very same way as Testosterone. That means that a molecule of Testosterone and a molecule of SARM would cause the same receptor to be active in the same way causing the same effects. I know this leads to more questions. So let's address them:
Excellent question. We only recently discovered the reason to this. The prevailing theory that was well substantiated, states that each tissue type have many co-regulatory molecules in the cells, that interact with the Androgen receptor and modulate its activity level. That means that skeletal muscles and the prostate would have a different array of these co-regulatory molecules. We now know that SARMs do not only activate the Androgen receptor, but are also differently affected by these regulatory proteins, that could suppress the SARMs' effect. That is why a SARM could be highly active in skeletal muscles, and less in the prostate. That also explains why one SARM may have a slightly different biological activity than another SARM.
Short answer: Yes.
Better answer: It depends.
Full answer: Since a SARM and Testosterone act on the same receptor, they will “compete”. However, some competition would result in relative inhibition, while other competition would result in relative amplification.
Let's imagine an athlete supplementing with Testosterone. Now he's adding a SARM... RAD-140 for example. This is the effect we would expect:
In the skeletal muscle you added a SARM to Testosterone, meaning you added more ligands, (or activating molecules) to the Androgen receptor. It would be molecularly equivalent to adding more Testosterone, since now you have more freely acting agents that bind and activate the Androgen receptors in that skeletal muscle.
In the prostate you also have those two compounds completing on binding to the Androgen receptor, but now there is a negative interaction the SARM has with the aforementioned co-regulatory molecules that exist in the prostate but not in the skeletal muscle. In this case when the SARM binds, the Androgen receptors is rendered less active. In such a way a SARM can either amplify or mitigate the activity of Testosterone in different tissues in the human body. Research on RAD-140 involving both cellular and animal models has actually supported this.
Thank you for reading.
Don't be basic. Don't be a meat-head. Don't be a cliche.
Muscle is power, knowledge is power. Have BOTH.
How does the Androgen receptor work?
The Androgen receptor is a nuclear type of receptor. That means, when the Androgen receptor binds its ligand (=activator molecule), e.g. Testosterone, the receptor turns to its activated confirmation (=molecular shape); In it's activated form, it engages with the DNA inside the cell, and causes the synthesis of effector proteins that cause the biological effects. When the ligand dissociates, or unbinds from the Androgen receptor, it goes back to its inactive confirmation, disengages the DNA, and the effector proteins will no longer be synthesized.
What determines if the Androgen receptors are activated or not?
The overwhelming majority of receptors in the human body, have a baseline activity. That means that given the total number of receptors in the human body, a fraction would be active, while a fraction would be inactive at any point in time. This is determined by the concentration of the ligand, in this case – Testosterone, in the circulation.
This means, that taking exogenous Testosterone causes an increase in free Testosterone concentration, which causes a greater fraction of the Androgen receptors to be bound and rendered active. Once the free Testosterone concentration decreases (i.e. You stop taking exogenous Testosterone) a fraction of the Androgen receptors would go back to their inactive state.
Do Androgen receptors “clear”? Do they “reset”?
This is where you get a lot of stupid statements made. The cells do not classically increase or decrease the number of Androgen receptors. There is a set amount. The effects mediated by these receptors are exclusively due to the ratio of active to inactive receptors. This is regulated by the concentration of the ligand (e.g. Testosterone).
That also means that above a certain amount of exogenous Testosterone – any additional amount wouldn't have an additional effect, since receptors have achieved saturation. In this case – more Testosterone doesn't mean more effect, but it may indeed result in more side effects.
How can one make more Androgen receptors?
The Androgen receptor is a protein that ages. As some receptors age and stop working, they are degraded while other are made. Receptors are degraded and synthesized at the same rate - that keeps the total number of receptors stable within the cell. You cannot “make” more Androgen receptors nor can you “clear” your Androgen receptors any more than you can “clear” all of your red blood cells and replace them with brand new ones.
The number of Androgen receptors any one person has in a cell is genetically pre-determined. That also explains why certain individuals will be much more responsive to steroids than others. Genetics is everything when it comes to the quantity and responsiveness of your receptors.
If one cannot “clear” or “reset” the Androgen receptors in his/her body, how does one properly maintain them?
You cannot affect the number or "maintain" your Androgen receptors, but you CAN reduce their potency, affinity, and potentially maximal number of receptors per cell if you expose yourself to high amounts of exogenous Testosterone before the age of 22-25.
If all this is true, how come Testosterone and Trenbolone work in the same way, but one is way stronger than the other?
One more variable of receptor activation is dictated by a term called ligand affinity. That means that some ligands (=activator molecules) once bound stay bound for a much longer period of time, while others stay bound for a lesser period of time. If Trenbolone, for example, activates an Androgen receptor and stays bound for an extended period of time, that Androgen receptor would remain active continually causing biological effects without a pause.
That also explains why you cannot replicate a high dose of Trenbolone with a super duper high dose of Testosterone. Simply because even if you have overwhelming concentration of Testosterone, you wouldn't be able to change the fact that at any given time some of these ligands would “jump off” the receptor, which would be rendered inactive until the next ligand "jumps on" to activate it.
How do SARMs activate the Androgen receptor differently than Testosterone?
Here is another major point of confusion, mainly due to the fact that people that are quick to dispense advice and explanations have the same scientific background in biochemistry, pharmacology and endocrinology as Dr. Pepper.
SARMs activate the Androgen receptor in the very same way as Testosterone. That means that a molecule of Testosterone and a molecule of SARM would cause the same receptor to be active in the same way causing the same effects. I know this leads to more questions. So let's address them:
If SARMs act exactly in the same way as Testosterone, how is it possible they are selective to some tissues? Also how is it possible that different SARMs have slightly different effects?
Excellent question. We only recently discovered the reason to this. The prevailing theory that was well substantiated, states that each tissue type have many co-regulatory molecules in the cells, that interact with the Androgen receptor and modulate its activity level. That means that skeletal muscles and the prostate would have a different array of these co-regulatory molecules. We now know that SARMs do not only activate the Androgen receptor, but are also differently affected by these regulatory proteins, that could suppress the SARMs' effect. That is why a SARM could be highly active in skeletal muscles, and less in the prostate. That also explains why one SARM may have a slightly different biological activity than another SARM.
Can SARMs change the degree to which Testosterone activates the Androgen receptor?
Short answer: Yes.
Better answer: It depends.
Full answer: Since a SARM and Testosterone act on the same receptor, they will “compete”. However, some competition would result in relative inhibition, while other competition would result in relative amplification.
Let's imagine an athlete supplementing with Testosterone. Now he's adding a SARM... RAD-140 for example. This is the effect we would expect:
In the skeletal muscle you added a SARM to Testosterone, meaning you added more ligands, (or activating molecules) to the Androgen receptor. It would be molecularly equivalent to adding more Testosterone, since now you have more freely acting agents that bind and activate the Androgen receptors in that skeletal muscle.
In the prostate you also have those two compounds completing on binding to the Androgen receptor, but now there is a negative interaction the SARM has with the aforementioned co-regulatory molecules that exist in the prostate but not in the skeletal muscle. In this case when the SARM binds, the Androgen receptors is rendered less active. In such a way a SARM can either amplify or mitigate the activity of Testosterone in different tissues in the human body. Research on RAD-140 involving both cellular and animal models has actually supported this.
Thank you for reading.
