Simple question regarding upregulation of AR

General Discussion
#1

Hey simple question regarding the theory that our disease is caused by the up regulation of the AR receptor. The idea being (in my best explanation) that because DHT was sent plummeting, the body reacted by overexpressing the AR receptor in an effort to maintain a hormonal balance. Then when DHT levels rose back to normal levels, the receptors we’re too expressed, or in a sense overwhelmed, causing a crash of the whole system. For those that have a better understanding, please feel free to reply with it.

I have two basic questions:

  1. Why does the body not automatically reset the receptor expression to its normal state once DHT is reintroduced at normal levels.
  2. If the receptor state doesn’t go back automatically, then how do we reduce the expression of the AR receptor. Clearly just adding a bunch of DHT doesn’t work, it usually just leads to a crash or making matters worse. What actual proven scientific methods that allow for the receptor to down-regulate back to its baseline expression?

These seem like simple enough questions to me that have probably been answered on this site. But can someone clearly explain why we are unable to get our receptors back to their normal state (if in fact, this is what is wrong with us). I’d rather not use the theory that FIN caused an epigenetic change to the receptor as a reason here if possible, although that could be what is happening.

Thank you!

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#2

The problem is, from my basic understanding, that receptors up and down regulate all the time. That’s why its called “regulate” because the body is intentionally changing sensitivity. This happens with drug tolerances all the time, and the body then re-regulates (like if you take a break from coffee you will become sensitive to it again).

So maybe epigentic is the only explanation for a permanent change in expression, but who knows. Bodybuilders do crazy things to their body and “cycle” and the body seems to adjust.

#3

This is my exact confusion. Why in this situation do the receptors not regulate to meet the presence of dht? Again, if this theory is indeed what is occurring…

Always been a bit confused as to the veracity of the theory that receptors become permanently upregulated. Although, a hallmark symptom of the syndrome is resistance to androgens… so something is up.

#4

Hi Scott,

Bear in mind that while this is theoretical in terms of a root driver since awors paper 8 years ago, it is not theoretical in terms of findings in PFS patients. This has been confirmed, and significant (double that of controls) overexpression of the AR has been confirmed in study of the penile skin of PFS patients reporting penile atrophy and sexual symptoms, at an average of five years after cessation. This is noted in the most recent literature reviews as a potential driver. As for your questions, although they may seem simple unfortunately that is not the case.

#5

Thanks @axolotl

Would it not make sense to lower dht to previous fin levels then SLOWLY turn up dht levels over time to allow the receptor to slowly regulate? Something tells me the sudden cold turkey of quitting finasteride may have led to the bodies inability to reset the receptor.

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