20/04/2008
Mistral
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Why testosterone is useless without dht
Who here thinks that DHT is just a stronger version of testosterone?
Well, I’m here to tell you that the DHT has unique benefits that testosterone doesn’t have, and this is why it’s important to maximize your DHT.
You can have high levels of testosterone and still feel like you have low androgens because your DHT is not on point and/or your 5 alpha to 5 beta reductase ratio is not being optimized.
DHT basics
So we do know that DHT is about 10 times stronger than testosterone. This is because DHT has 4 times higher binding affinity to the androgen receptor than testosterone. And DHT binds 3 to 5 times longer to the androgen receptor than testosterone
DHT is much more capable of exerting what it’s supposed to do than testosterone.
Even though DHT is found in 10 times lower amounts than testosterone, it’s 10 times stronger. If you maximize 5 alpha-reductase (5AR) and testosterone, you’ll have a much greater total androgen pool than someone with low 5AR. This means you will have more androgens to bind to the androgen receptor, making you more anabolic and androgenic.
Heat shock protein 70 and 90 are bound to the androgen receptor. Once the androgen binds to the receptor, the heat shock proteins detach and the androgen receptor can enter the nucleus. Once inside, it binds to the androgen response element (ARE). Various cofactors can then also bind to the AR/ARE complex. There are also multiple androgen response elements as well as co-regulators
Selective ARE is a mechanism for ligand-specific regulation of AR function (R).
So as you can see, it’s more complicatedthan just binding to the androgen receptor and exerting 1 action.
As you can see from the structures above, these androgens are about 95% similar, but they vary a lot in how potently they bind to the androgen receptor.
And they induce slightly different configurations despite binding to the same receptor.
It’s the same thing with SARMs. SARMs act on the androgen receptor.
The hypothesis for how SARMs work, and how they are anabolic but not androgenic, are those two hypotheses.
1)Hypothesis 1 (coactivator hypothesis): This hypothesis presumes that testosterone-bound AR and SARM-bound AR have different coregulator proteins, which leads to transcriptional activation of a differentially regulated collection of genes
Without DHT you have weaker AR signalling.
So as I mentioned, the androgen receptor binds differently to these different compounds, and this creates the conformational modifications in the ligand binding domain induced by ligand binding and might change surface topology, thus modifying protein-to-protein interaction between the androgen receptor and other co-regulators.
It’s different co-regulators and different androgen response elements. And this is actually why studies have shown that there are unique benefits to DHT that testosterone does not have. So when you give, for example, DHEA or testosterone to a human or an animal, and you inhibit 5 alpha-reductase with, for example, finasteride, you don’t get the same benefit as not blocking it, right?
So there are unique benefits to DHT. A lot of people would say that DHT plays no role in the adult. You only need testosterone. That’s not true. DHT is not just a stronger version of distortion. It’s different and induces different changes to the androgen receptor and gives unique benefits that testosterone will not give you.
So you might be thinking: “Well, I’m just going to use DHT.” Now that’s also a wrong conclusion because there are unique benefits of testosterone and DHT. If you were to use just DHT, you would miss out on the benefits of testosterone. But if you use just testosterone and you don’t optimize your 5 alpha reductase enzyme or block it, you might miss out on the benefits of DHT.
Make sure that your 5 alpha reductase is working properly so you can convert your testosterone and DHEA and androstenedione into the 5 alpha reduced steroids so you can benefit from that.
Also, 5AR doesn’t just create DHT, it also deactivates cortisol and aldosterone and activates progesterone to create allopregnanolone. 5 alpha reductase is very important, not just for creating DHT.
Tags:@Hexmask
Who here thinks that DHT is just a stronger version of testosterone?
Well, I’m here to tell you that the DHT has unique benefits that testosterone doesn’t have, and this is why it’s important to maximize your DHT.
You can have high levels of testosterone and still feel like you have low androgens because your DHT is not on point and/or your 5 alpha to 5 beta reductase ratio is not being optimized.
DHT basics
So we do know that DHT is about 10 times stronger than testosterone. This is because DHT has 4 times higher binding affinity to the androgen receptor than testosterone. And DHT binds 3 to 5 times longer to the androgen receptor than testosterone
Androgen Receptor Structure, Function and Biology: From Bench to Bedside - PMC
The actions of androgens such as testosterone and dihydrotestosterone are mediated via the androgen receptor (AR), a ligand-dependent nuclear transcription factor and member of the steroid hormone nuclear receptor family. Given its widespread ...
www.ncbi.nlm.nih.gov
DHT is much more capable of exerting what it’s supposed to do than testosterone.
Even though DHT is found in 10 times lower amounts than testosterone, it’s 10 times stronger. If you maximize 5 alpha-reductase (5AR) and testosterone, you’ll have a much greater total androgen pool than someone with low 5AR. This means you will have more androgens to bind to the androgen receptor, making you more anabolic and androgenic.
Androgens binding to the androgen receptor
Here’s what happens when androgens bind to the androgen receptor.Heat shock protein 70 and 90 are bound to the androgen receptor. Once the androgen binds to the receptor, the heat shock proteins detach and the androgen receptor can enter the nucleus. Once inside, it binds to the androgen response element (ARE). Various cofactors can then also bind to the AR/ARE complex. There are also multiple androgen response elements as well as co-regulators
Complexities of androgen action - PubMed
Androgens mediate a wide range of processes during embryogenesis and in the adult. In mammals, the principal androgens are testosterone and its 5alpha-reduced metabolite, 5alpha-dihydrotestosterone (DHT). Although these androgenic hormones are diverse in character, it is believed that their...
pubmed.ncbi.nlm.nih.gov
Differential regulation of testosterone vs. 5α-dihydrotestosterone by selective androgen response elements - Molecular and Cellular Biochemistry
There are two major physiological androgens, testosterone (T), and 5α-dihydrotestosterone (DHT), which induce different responses in mammals. These androgens regulate the target gene transcription via binding to and activating the same androgen receptor (AR). The molecular mechanisms that differ...
link.springer.com
Selective ARE is a mechanism for ligand-specific regulation of AR function (R).
So as you can see, it’s more complicatedthan just binding to the androgen receptor and exerting 1 action.
Different androgens on the androgen receptor
Because the structure of each androgen is different, they will bind differently to the androgen receptor and exert different effects.As you can see from the structures above, these androgens are about 95% similar, but they vary a lot in how potently they bind to the androgen receptor.
And they induce slightly different configurations despite binding to the same receptor.
It’s the same thing with SARMs. SARMs act on the androgen receptor.
The hypothesis for how SARMs work, and how they are anabolic but not androgenic, are those two hypotheses.
1)Hypothesis 1 (coactivator hypothesis): This hypothesis presumes that testosterone-bound AR and SARM-bound AR have different coregulator proteins, which leads to transcriptional activation of a differentially regulated collection of genes
- Meaning, SARMs, and androgens regulate genes differently despite acting on the same receptor.
- don’t know about you, but that makes little sense to me
Without DHT you have weaker AR signalling.
So as I mentioned, the androgen receptor binds differently to these different compounds, and this creates the conformational modifications in the ligand binding domain induced by ligand binding and might change surface topology, thus modifying protein-to-protein interaction between the androgen receptor and other co-regulators.
Summary
It’s complex stuff, but because the structures of these molecules are different, they induce different changes when binding to the same receptor. And also testosterone and DHT induce different androgen response elements.It’s different co-regulators and different androgen response elements. And this is actually why studies have shown that there are unique benefits to DHT that testosterone does not have. So when you give, for example, DHEA or testosterone to a human or an animal, and you inhibit 5 alpha-reductase with, for example, finasteride, you don’t get the same benefit as not blocking it, right?
So there are unique benefits to DHT. A lot of people would say that DHT plays no role in the adult. You only need testosterone. That’s not true. DHT is not just a stronger version of distortion. It’s different and induces different changes to the androgen receptor and gives unique benefits that testosterone will not give you.
So you might be thinking: “Well, I’m just going to use DHT.” Now that’s also a wrong conclusion because there are unique benefits of testosterone and DHT. If you were to use just DHT, you would miss out on the benefits of testosterone. But if you use just testosterone and you don’t optimize your 5 alpha reductase enzyme or block it, you might miss out on the benefits of DHT.
Make sure that your 5 alpha reductase is working properly so you can convert your testosterone and DHEA and androstenedione into the 5 alpha reduced steroids so you can benefit from that.
Also, 5AR doesn’t just create DHT, it also deactivates cortisol and aldosterone and activates progesterone to create allopregnanolone. 5 alpha reductase is very important, not just for creating DHT.
Tags:@Hexmask