In short terms It’s possible our cells have become non-respondent to androgens due to abnormal cellular reprogramming and at the root cause of this disease is hypermethylation of the androgen gene promoters causing permanent downregulation and overexpression. Circulating androgens that are required for maintenance can no longer bind to receptors essentially starving the tissues, the worse the methylation the worse off the PFS patient. As a downstream effect of the methylation it may be causing protein misfolding and putting too much stress on the endoplasmic reticulum, the ER functions to synthesise lipids, steroid hormones, the detoxification of harmful metabolic byproducts and the storage and metabolism of calcium ions within the cell. If there is an accumulation of misfolded proteins and the objectives of the ER are not achieved within a certain time span or the disruption is prolonged, the UPR aims towards apoptosis. Sustained overactivation of the UPR can have devastating health implications on the host and has been implicated in numerous prion diseases such as Alziemhers, Parkinson’s and Huntington’s it may well be that Post Finasteride Syndrome is a Prion disease caused by abnormal methylation.
You seem to be thinking of diseases involving amyloid/fibril accumulation. Prions are self-perpetuating malignant forms of proteins that often form amyloids/fibrils.
Axolotl and I had a discussion about the possibility of grossly overexpressed AR forming amyloids since the poly-Q form of AR that leads to SMBA has been found to form aggragates. There was no insightful conclusion to that discussion.
That would be something to learn that PFS is transmissible though.
@Dubya_B why hasn’t someone just decided the real reason all these things happen because the liver takes a beating?
I hope that’s a joke?
Let me refrase. Liver cell death, unreversible alterations to the liver etc, which goes onto effect whole body systems, so a liver origin, obviously there’s been constant liver detox ideas which I believe futile. Which might be transmissible through an evolutionary aspect as seen in animals with certain increased exposures.
Seriously as someone that has taken accutane and finestride, finestride may as well have been placebo, so whatever it does it had already been altered in myself.
Anyway obviously I’m no expert so sorry if this sounds stupid.
Sorry, I misinterpreted that statement as “I have the one correct answer to post-drug syndromes; it’s the liver.”
If you mean to say that mis-folded proteins may be emanating from the liver to other tissues in the body, I’ve never seen any indication that this would be plausible.
Prions are the only malignant protein that self-propagate like that, and there is only one protein in humans known to be able to be induced into a malignant conformation in such a manner. There are other proteins that can form fibrils, but that is due to their accumulating more rapidly than they can be disintegrated by proteases. They don’t spread throughout the body.
Some illustrations: https://docs.google.com/presentation/d/1Cpc2nPNhBAJa4JLirSDBh1Y2aqkYiwIElVkwziBRD20/edit?usp=sharing
The anecdotal experiences here suggest that when raising testosterone they feel worse and better off when it is low so it got me thinking why is this occurring, does raising testosterone cause a further desensitisation of receptors and if so why?
The only explanation I could think of is that protein misfolding could be occurring due to hypermethylation of gene promoters, too much misfolded protein starts to accumulate in the tissues causing further receptor issues. But then that theory does not explain why PFS seems to occur in site specific tissues unless severe downregulation is causing androgen proteins to build up in tissues possibly due to a conformational change to the receptors making them extremely sensitive to androgens. I know axol has mentioned somatic mutations but from what I have read it seems to be permanent and would not explain why some people have improved over time.