What do we “know” about Pfs?

I’ve seen posts about overexpresion, posts about auto immunity, gene expression. Is there anything we KNOW about our condition at this point?

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Take a look at the published research page over at the PFS Foundation:

It’s vital work - and we need to fund more, together.

This is going to be a fairly long post so brace yourself.

  • From the Italian studies, we know that AR overexpression is taking place to some degree. Although they biopsied penile tissue, it is almost certain the same thing is going on in other parts of our body.

  • At first glance overexpression might sound like a good thing because it means androgenic characteristics will express more than normal, however that is not the case. Expression is like a bell curve, too little is bad, too much is bad, there’s a goldilocks level of expression that needs to be maintained for signaling to take place normally. This was demonstrated in DA Monks paper, where he genetically engineered mice to have overexpressed ARs in their muscular tissue, but instead of the expected result, he found that their tissue broke down. AR overexpression has also been demonstrated to be neurotoxic (kills brain cells) and cytotoxic (kills cells) in literature.

  • While we are born with a set of genes that don’t change, throughout our lives their expression changes due to environmental and other factors. How much a gene expresses is as important as what the gene does, because say (this is just a crude example) you have a gene that’s responsible for controlling dopamine release, and that gene’s expression is turned way up, then your brain has too much dopamine and you have symptoms like mania, psychosis, delusions, etc., but say it’s turned down low, then you have depression, anhedonia, low libido, etc. Needs to be maintained at a certain level. These genes’ expression are regulated by various processes such as methylation, acetylation, phosphorylation etc. When methylation occurs, methyl groups are added to the gene and that makes it express less. When methyl groups are removed from the gene, it expresses more. This thing also happens with acetylation, phosphorylation, and the other epigenetic regulatory mechanisms. What’s important to remember is that most of these processes are temporary, except for methylation. Methylation tends to stick, and once methyl groups are attached, it’s pretty difficult to get rid of them (like a crazy ex).

  • The current theory is that Finasteride has caused certain genes to become methylated, leaving us with an overexpressed AR. We don’t have definitive proof that this is going on in every cell in our body, but we know it’s going on in penile tissue, and based on anecdotal evidence it’s probably going on almost everywhere else depending on the severity of our condition.

  • We also know that we have lower neurosteroids than normal people, something that is seen in depressed individuals. This is most likely due to AR overexpression as well, or possibly the methylation of other genes responsible for neurosteroid synthesis.

  • The auto immunity theory came about from the observation that immunosuppressants improved the condition of some PFS sufferers. There is a post made by a member on another board explaining why, and if you want I can link you to it. TL;DR, some immunosuppressants increases 5AR1 activity, which increases neurosteroid synthesis.

  • The long and short of it is that there is an epigenetic disaster taking place, the chance of getting out of it (if you have severe side effects) is the same as Croatia winning the World Cup now (if you have minor sides, there’s a chance it will resolve, but might as well donate a small amount every month just in case it doesn’t. A dollar a day isn’t going to burn a hole in your wallet). As the above poster noted, we need funds to conduct more studies and get some answers. The technology to fix us is coming along nicely but we need a target, which we can only find with studies.

If you have any other questions, feel free to drop them on this thread.

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what’s the proposition here now?
we can demethylate these silenced genes with demethylating agent azaC(probably) and what do we do with AR overexpression??
there are no methylating agents,or we pray that after we demethylate the other silenced genes,a cascade will happen and somehow magically the overexpressed AR will methylate and return to normal?

Anyone with epigenetic knowledge can theorise regarding this?

well nothing in science is magic so I don’t think anyone can chime in on your post

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do u propose any logic or u just came to ruin the thread?

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think you beat me to ruining the thread when you stated science was magic. ill get em next time.

i quoted statements and asked for proposed treatment based on those facts

if u have any helpful idea ok
if not than we both should stop flaming the thread…

Let’s keep it friendly, guys.

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“When methylation occurs, methyl groups are added to the gene and that makes it express less. When methyl groups are removed from the gene, it expresses more.”

“The current theory is that Finasteride has caused certain genes to become methylated, leaving us with an overexpressed AR.”

But if certain genes became methylated wouldn’t that entail they are being expressed less? You said methylation leads to genes expressing less and that our AR is methylated but overexpressing. Maybe I’m missing something

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I read the post by @borax and thought "Finally, I almost understand this PFS.

Then @Erik pointed out the methyl contradiction…now I’m back to the “dunno what’s going on” stage.

To think at one point I used to be a smart man. Jim

I spoke to Borax and he said certain genes are up-regulated and certain genes are down-regulated. So certain genes are methylated when they shouldn’t be and vice versa. That’s at least his interpretation.

I’m sure you’re still a smart man, Jim. Even if that’s temporarily obscured.

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