Androgen Receptor upregulation for receptor resensitization

Science
#1

I read the paper, where the theory goes, that the androgen signaling is silenced. In short the theory goes like this: There is a 5alpha-reductase inhibition, which leads to less DHT. The body tries to come up for that and expresses more androgen receptors. After discontinuation of the drug there is a spike in DHT which leads to silencing of the androgen signaling. This is linked to 3alpha-HSD and leads to less Allopregnanolone being available.

I found a study which says Progesterone leads to Androgen-receptor upregulation. (https://pubmed.ncbi.nlm.nih.gov/11673911/)
Also I found another study which says Mifepristone leads to androgen receptor upregulation. (https://pubmed.ncbi.nlm.nih.gov/24239933/)

So perhaps this is why there are some successes with those protocols, because the new receptors lead to a resensitization and people got their androgen receptor signaling back?

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#2

I just found a german thesis, which has the result, that receptor resensitization is caused by the synthesis of receptors.

“In der vorliegenden Arbeit konnte gezeigt werden, dass unter physiologischen (Langzeit-) Bedingungen die IP-R Resensibilisierung v.a. auf Rezeptorneusynthese beruht.”

#3

Where is that paper? It seems to me that if a symptom of PFS is overexpressed androgen receptors, then I don’t see how trying to overexpress them even more would be helpful.

#4

Does anybody know if these AR receptors will come back up to normal levels after inhibition? Is there any scientific literature that examines this? Is there any literature out there regarding brain receptor damage and receptor regrowth or recovery?

#5

I’m not sure which paper you’re referring to, but if it’s the one written by Awor & Mew, it’s over 10 years old. Awor and Axo both moved beyond the idea the AR is silenced and instead proposed it is overexpressed: https://www.propeciahelp.com/post-androgen-deprivation-syndrome-abstract/ and specifically this chapter: https://www.propeciahelp.com/ar-deregulation-as-a-key-pathological-driver-of-pfs/

Which was then confirmed by Baylor’s results: https://www.pfsnetwork.org/science/differential-gene-expression-in-post-finasteride-syndrome-patients

I know you’re desperate for relief, but these scientific concepts and mechanisms are simply far beyond any of our grasps. We don’t go to YouTube if we want to build a skyscraper - we defer to structural engineers and architects with experience. If the powerlines around our house are down, we don’t search for a “how-to” guide online to fix them - we call experienced electricians and line workers.

The same should hold true here. For the better part of two decades, we didn’t have experts willing to help us, or to study what is occurring in PFS. Now we do. We have an amazing team of researchers who are genuinely at the top of their respective fields. We need to defer to them, fund them, and allow them to do their work.

It may take time, sure, but the sooner we work together to fund them, the sooner we can start to test treatments with a modicum of scientific accuracy.

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#6

Yes it was the paper from 2010. Thanks for sharing the current view. I will read it in the next days. I try to understand what it is going the best way I can, also that I can discuss it with my doctor. Thanks to the scientific concepts proposed on this forum he was willing to look further into it. Without it, there would not have been a clue for what to look for, I would have gotten the explanation that it’s not possible the drug is still in my system and most likely my case would already be closed and I would feel miserable that I don’t get any support. So I’m very happy that I’m taken serious, again thank you for the work which has been done here.

Of course I would want a professional to build my house. But there is sth in between doing nothing and getting it done by somebody else, and that is checking the current studies and discussing it. Perhaps someone can elucidate sth which leads to me getting a better understanding which improves my chances of getting the right treatment, bc me personally I want to try sth asap.

I agree, we should fund the researchers. I hope they find the best way to treat this as fast as possible.

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#7

This is the right attitude to have! Thank you :heart:

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