Androgen Receptors Question

alex00

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Hello I have a question to ask you, Does topical use of androgens like DHT on a tissue cause an up-regulation or down-regulation of androgen receptors in that tissue? And is it true that the sensitivity of androgen receptors to the applied topical hormone decreases over time or remains unchanged?
Thanks a lot.
 

Constatine

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It causes an upregulation of androgen receptors in the tissues. I would guess it increases over time due to the upregulation.
 

Wagner83

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alex00

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It looks like there are ways to accelerate /increase the inactivation of androgens in tissues:
Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans - ScienceDirect
3a hsd (per haidut).

Wasn't there a discussion on some types of receptors being upregulated while others weren't? I wonder if diokine was the one who talked about this.

As usual, I know nothing about biology but still forward information once in a while.
I can't find anything here on the forum that talks about this
 
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alex00

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It causes an upregulation of androgen receptors in the tissues. I would guess it increases over time due to the upregulation.
Excuse me but a chemical applied on a tissue for a prolonged time does not desensitize the receptors to that chemical? and thus causes down-regulation of receptors?
Maybe I'm wrong. Thanks
 
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Excuse me but a chemical applied on a tissue for a prolonged time does not desensitize the receptors to that chemical? and thus causes down-regulation of receptors?
Maybe I'm wrong. Thanks

Upregulation.

You ask a question and proceed to question the answers?

Maybe you should look into studies then...
 

Constatine

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Excuse me but a chemical applied on a tissue for a prolonged time does not desensitize the receptors to that chemical? and thus causes down-regulation of receptors?
Maybe I'm wrong. Thanks
Not all chemicals are the same. Androgens typically upregulate the androgen receptor. It's a positive feedback loop. Excess androgens can downregulated androgen production, but as far as I know it's receptors are upregulated.
 
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alex00

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Upregulation.

You ask a question and proceed to question the answers?

Maybe you should look into studies then...
Ok, thank you
Not all chemicals are the same. Androgens typically upregulate the androgen receptor. It's a positive feedback loop. Excess androgens can downregulated androgen production, but as far as I know it's receptors are upregulated.
Ok, i understood. But i don't understand one thing
If I apply topical DHT on a specific tissue ( like penis ) increases the density and up-regulates AR also there (in the tissue) or instead increases the density and up-regulates AR in whole body but in the specific tissue where I apply the DHT after a time the receptors become insensitive and down-regulated?
Thanks a lot.
 
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Constatine

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Ok, i understood. But i don't understand one thing
If I apply topical DHT on a specific tissue ( like penis ) increases the density and up-regulates AR also there (in the tissue) or instead increases the density and up-regulates AR in whole body but in the specific tissue where I apply the DHT after a time the receptors become insensitive and down-regulated?
Thanks a lot.
It enters circulation so the whole body but it is briefly very concentrated in the applied tissues. Where you apply the DHT should not become insensitive.
 

Wagner83

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If You Don't Want Low Testosterone DO NOT FAST

From @haidut:

The increase in AR density is an effect that BOTH progesterone and androgens like T/DHT have. I mentioned this in another earlier message and sent a study as well as that post by AretnaP which showed the same effects. There are a ton of studies on this and the synthetic androgen R1881 is often used to increase AR density in those studies. So, taking either progesterone or T/DHT will make you more sensitive to androgens, not less. As such, the theory about desensitization of androgen receptors is not supported by evidence, at least there is no desensitization from androgens and P4.​
[...]
The studies I listed checked nuclear AR, not membrane ones. I understand there is a difference between the two, but the whole discussion initially from that group was on androgens desensitizing nuclear receptors. Now there is a change of course that is various receptors and the effects varies upon the state of the cell. Yes, of course is depends on the state of the cell. That was the whole initial discussion that I kept reintroducing - the NAD/NADH ratio, thyroid levels, fatty acid composition of the cell, etc all come into play. But the effect of androgens on (nuclear) AR is largely to increase their density.​

[... ]

Btw, here is a study showing T administration decreased cytoplasmic AR density and increased nuclear AR density. http://atvb.ahajournals.org/content/atvbaha/5/6/659.full.pdf "...Injection of intact female AXC rats with testosterone caused a 90% reduction in androgen receptor content of aortic cytoplasmic preparations which was quantitatively accounted for by the appearance of androgen receptors in nuclear preparations from the same tissues (Table 2). Total aortic androgen receptor content of testosterone-injected female rats was not significantly different from the cytoplasmic fraction androgen receptor content of control females, p < 0.5 (Table 2). Injection of intact females with testosterone caused partial (50%) depletion of androgen receptor content of myocardial cytoplasmic preparations and comparably increased androgen receptor content of nuclear preparations from the same tissues (Table 2). Total myocardial androgen receptor content of testosterone-injected female rats was not significantly different from myocardial cytoplasmic fraction androgen receptor content of control females, p < 0.5 (Table 2)."​
 
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alex00

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If You Don't Want Low Testosterone DO NOT FAST

From @haidut:

The increase in AR density is an effect that BOTH progesterone and androgens like T/DHT have. I mentioned this in another earlier message and sent a study as well as that post by AretnaP which showed the same effects. There are a ton of studies on this and the synthetic androgen R1881 is often used to increase AR density in those studies. So, taking either progesterone or T/DHT will make you more sensitive to androgens, not less. As such, the theory about desensitization of androgen receptors is not supported by evidence, at least there is no desensitization from androgens and P4.​
[...]
The studies I listed checked nuclear AR, not membrane ones. I understand there is a difference between the two, but the whole discussion initially from that group was on androgens desensitizing nuclear receptors. Now there is a change of course that is various receptors and the effects varies upon the state of the cell. Yes, of course is depends on the state of the cell. That was the whole initial discussion that I kept reintroducing - the NAD/NADH ratio, thyroid levels, fatty acid composition of the cell, etc all come into play. But the effect of androgens on (nuclear) AR is largely to increase their density.​

[... ]

Btw, here is a study showing T administration decreased cytoplasmic AR density and increased nuclear AR density. http://atvb.ahajournals.org/content/atvbaha/5/6/659.full.pdf "...Injection of intact female AXC rats with testosterone caused a 90% reduction in androgen receptor content of aortic cytoplasmic preparations which was quantitatively accounted for by the appearance of androgen receptors in nuclear preparations from the same tissues (Table 2). Total aortic androgen receptor content of testosterone-injected female rats was not significantly different from the cytoplasmic fraction androgen receptor content of control females, p < 0.5 (Table 2). Injection of intact females with testosterone caused partial (50%) depletion of androgen receptor content of myocardial cytoplasmic preparations and comparably increased androgen receptor content of nuclear preparations from the same tissues (Table 2). Total myocardial androgen receptor content of testosterone-injected female rats was not significantly different from myocardial cytoplasmic fraction androgen receptor content of control females, p < 0.5 (Table 2)."​
Thank you for the information. But exactly what changes between cytoplasmic AR and nuclear AR? have different body functions?
 

Yggr

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Perhaps cytoplasmic reductions cause a decrease uptake of androgens.
 
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alex00

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Perhaps cytoplasmic reductions cause a decrease uptake of androgens.
Do you think it? So if this were true the theory of desensitization of androgen receptors to applied androgens would be true?
 

Yggr

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Well there must be some sort of feedback loop or it would just self perpetuate higher and higher signaling but I’m sure this doesn’t occur.

Maybe I’m missing something of lots
 
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alex00

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Well there must be some sort of feedback loop or it would just self perpetuate higher and higher signaling but I’m sure this doesn’t occur.

Maybe I’m missing something of lots
If You Don't Want Low Testosterone DO NOT FAST

From @haidut:

The increase in AR density is an effect that BOTH progesterone and androgens like T/DHT have. I mentioned this in another earlier message and sent a study as well as that post by AretnaP which showed the same effects. There are a ton of studies on this and the synthetic androgen R1881 is often used to increase AR density in those studies. So, taking either progesterone or T/DHT will make you more sensitive to androgens, not less. As such, the theory about desensitization of androgen receptors is not supported by evidence, at least there is no desensitization from androgens and P4.​
[...]
The studies I listed checked nuclear AR, not membrane ones. I understand there is a difference between the two, but the whole discussion initially from that group was on androgens desensitizing nuclear receptors. Now there is a change of course that is various receptors and the effects varies upon the state of the cell. Yes, of course is depends on the state of the cell. That was the whole initial discussion that I kept reintroducing - the NAD/NADH ratio, thyroid levels, fatty acid composition of the cell, etc all come into play. But the effect of androgens on (nuclear) AR is largely to increase their density.​

[... ]

Btw, here is a study showing T administration decreased cytoplasmic AR density and increased nuclear AR density. http://atvb.ahajournals.org/content/atvbaha/5/6/659.full.pdf "...Injection of intact female AXC rats with testosterone caused a 90% reduction in androgen receptor content of aortic cytoplasmic preparations which was quantitatively accounted for by the appearance of androgen receptors in nuclear preparations from the same tissues (Table 2). Total aortic androgen receptor content of testosterone-injected female rats was not significantly different from the cytoplasmic fraction androgen receptor content of control females, p < 0.5 (Table 2). Injection of intact females with testosterone caused partial (50%) depletion of androgen receptor content of myocardial cytoplasmic preparations and comparably increased androgen receptor content of nuclear preparations from the same tissues (Table 2). Total myocardial androgen receptor content of testosterone-injected female rats was not significantly different from myocardial cytoplasmic fraction androgen receptor content of control females, p < 0.5 (Table 2)."​
Therefore you are not sure that the depletion of cytoplasmic AR caused by the administration of androgens gives a desensitization of the tissue to the androgen administered. Right?
 

Yggr

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Correct, I am unsure. I a man just speculating as to why the effect diminish over time.
 

Wagner83

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Correct, I am unsure. I a man just speculating as to why the effect diminish over time.
Did you experience this? Can you share more on what you supplemented, how much and for how long before effects diminished?
As suggested in one of my post above, perhaps enzymes could become more efficient at inactivating androgens?
 

bdawg

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Nice one - I read that as androgen agonists like DHT reverse some of the age related reduction in androgen sensitivity (AR MRNA + Androgen Binding) in the peniz
  • This contrasts with the marked in vivo decline of both AR mRNA and androgen binding in the penile smooth muscle of adult rats, which appears to be responsible for the cessation of androgen-dependent penile growth upon sexual maturation
  • ARs were up-regulated in A-PSMC (adult rats) by R-1881.
  • Contact inhibition of A-PSMC combined with serum depletion and androgen deprivation down-regulated AR mRNA levels, and dihydrotestosterone (DHT) counteracted this effect
 

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