hey axolotl. havent known that. i always thought when dht receptors upregulate they will downregulate again after you stop taking the drug. my fault 
however, i dont have the scientific knowledge for this. i only wrote down the mechanism what they assume from pssd. because i believe its nearly the same mechanism. thank you for your input !
Saying that something up regulates doesn’t help. It’s permanently unregulated which is whole another animal. The whole point of receptors are to up and down regulate. Id they didn’t, the consequences would be dire.
An analogy has been made here before between the upregulation of AR due to a silencing of the AR signal and someone screaming because they cannot hear themselves speak.
Does this clear things up?
So gene silencing is the real issue and upregulation is just a byproduct…
I believe so, yes. From my understanding, there is either a gene that interacts with the AR to allow it to function correctly that is silenced, or overproduction of a gene product that blocks its normal effect.
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What do you think about upregulation of 3α-HSD and 17β-HSD? A study says that my substances upregulate these two enzymes! Also SSRI! And if this is the cause? A total venom!
The 5-ari withdrawal theory paper provides evidence that total 3a-HSD activity is lowered in people with a dysfunctional androgen receptor due to genetic origins and applies this to explain the same of PFS patients. 3a-HSD activity is dependent on AR signalling to some degree.
Also, if a substance drastically increases 3a-HSD activity, it is liable to lower 5-ar metabolites, like DHT, at the same time, producing the same net effect on androgen levels as blocking 5-ar.
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If its a gene problem, do we need some demethylation ? And why some people are practicing methylation protocols when it comes to ‘‘treating’’ undiagnosed problem.
Are there any treatments for genetic problems?
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Hei amico, tu hai PFS da intagratore di 5-HT?
A demethylating agent might help depending on what the problem is. We just don’t know for sure yet. One issue is that without targeted DNA demethylation, we can’t be sure we are having sufficient effect to turn the suspect gene back on without damaging off-target effects. I think it is too speculative to undergo a treatment of this calibre without having a therapeutic target in sight first. Some people are doing these types of treatments because they were popular for some time in the CFS community and some were seeing relief from treating a suspected lack of methyl donors based on 23andMe data showing that they had lower-functioning copies of methyl-donor producing genes. I got burnt badly last Summer by playing around with methylation supplements simply based on some other PAS patients saying they felt more energetic while taking them. I’m still suffering the effects and regret being that stupid.
We don’t have a problem due to bad genetics though, only a possible increased susceptibility. We were all fine before taking whatever caused this condition to develop in us.
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Yes, 5-HTP combined with SSRI…
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I know this isn’t going to help, but did tour doctor tell you take two serotonin drugs at the same time? Seems like this could generally be dangerous in terms of serotonin syndrome.
I did not know … There was nothing written about the side effects on the 5-htp bug …
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I’m no endocrinologist, nor biologist. My background is in Electrical Engineering and systems control, and whilst I understand that many on this forum know considerably more about the potential processes at play here, I wish to bring attention to something which I feel has been overlooked of late.
That is the notion that perhaps our issue isn’t epigenetic, but rather a case of hysteresis of the HPT axis.
The body is a complex system and perhaps Finasteride and it’s cessation forced the body into an extremity wherein it became ‘locked’. Think of it as a valley whereby the HPT axis is operating in an abnormal state of operation. Increasing androgens to some degree may not be enough to push the system out of that state. In fact it could have the negative effect and push it further into the abnormal state.
Perhaps a more detailed understanding of PFS will allow us to realise exactly what needs pushing and in which direction in order to restore the HPT axis to a state of normalcy. I hope that the soon to be released Baylor study will provide illumination as to whether PFS is due to an epigenetic change or not.
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If it is permanent gene or ar problems why we get brief recovery in-between
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just a techie here but i get it, hysteresis is a documented phenomen in the brain for example oxytocin and the rubber hand illusion
crispr is another example, it can change a cell but the whole system is impossible
we need to brainstorm about genetic switches and stop wasting time on isolated agonists
something as simple as TRT and nuking your estrogen could be an answer but i see no one trying it
yet people try all sort of crap
if 3a-HSD in PFS patients is low then how you explain decreased DHT and increased 3a-diol in their brain?? the enzyme responsible for DHT > 3a-diol conversion is not 3a-HSD??
https://sci-hub.tw/https://doi.org/10.1016/j.jsbmb.2017.04.003
has anyone tried medroxyprogesterone(3a-HSD blocker)?? it is otc here
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You brought up a good point. There are multiple isoforms of 3a-HSD enzymes and some of the 3a-HSDs have been found to favor the oxidative reaction. This really complicates the matter.
Going by blood test results of members of this forum, A-diol G is greatly reduced in PFS patients:
There seems to be a trend of normal DHT levels and low A-diol-G that would indicate a net deficiency of 3a-HSD activity.
Something that was very surprising was Melcagni’s team finding normal levels of A-diol-G
the problem with bloodwork is that plasma almost never reflects brain levels, usually they are opposed like a seesaw of feedback
we must be looking at different data then, the table shows 3a-diol increased both in plasma and brain
the latter having AT LEAST a 5x higher 3a-diol / DHT ratio in PFS patients, which means that reductive 3a-HSD is working hard…
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