Guys, i gathered some information from some people that who knows what they are talking about. Please read this and contribute, i hope this can help us and other PFS cases.
So a guy on T nation who studies medicine and pharmacy wrote me this on my PAS thread there. We talked a lot with this guy and he helped me a lot he thinks PFS works like this too:
It works like this.
1. There is an AR in the cytosol (water in the cell), it gets activated by AAS
2. It sets itself free from proteins (called HSPs) and travels (trans locates) into the cell nucleus
3. The AR has a region which binds to the ARE, a segment on the DNA
4. The receptor binds cofactors for transcription (depending on cell type, these are different)
5. The genes get transcribed (for example for muscle proteins) to mRNA
6. The mRNA gets translated into proteins
The androgen receptor itself is a protein. It gets destroyed like any other protein when itās dysfunctional and then new AR gets synthesized.
What isotretinoin (or retinoids) does is, it interferes with step 4 and 5 as itās receptor can bind other receptors.
What can happen is, through retinoids the expression of genes can be changed permanently as the regulation cascade changes when you block these steps.
Cells are 24/7 fine tuning these cascades so the cell can switch off and on genes through other ways. One way is, than the cell can change Step 1 if it inactivates the gene for the AR, so there is less AR. It can also interfere with Steps 3,4,5 and 6. So when you interfere with the signaling cascades, the cell reacts with different mechanisms. One can be methylation of genes to shut them off.
Another PAS guy since 1991, who did intensive research on epigenetics and whose mother is a doctor, wrote me some things like this, im quoting some conversations between me and him:
HE: It is weirder than being bitten by a radioactive spider. (Talks about PAS and PFS)
HE: Hereās a neat factā¦ radiation damage: the epigenetic molecule bonds to the DNAā¦ they are 10,000 times weaker than the bonds holding the base pairs together.
So everyone who ever said radiation causes genetic damage, well, first comes the epigeneticā¦ and if you do nothing, then well the DNA needed a bunch of those genes just to stay together: whops. To the extent that there are existing therapies which decrease the severity of minor radiation damageā¦ thatās epigenetic molecules being spared, supplemented, etc.Nothing can be done about the truly broken DNA, yikes.
ME: Omg So hopefully our DNA is not brokenā¦ yet?
HE: Itās notā¦ or weād be breaking out in cancers. and we donāt
our damage is more selective, and gentle, haha
He: They donāt want to accept that, also, the levels (hormones) can be fineā¦ but there arenāt enough receptors to care. Or they are there, but no longer correct.
ME: But arenāt receptors always regenerate and re made? My prof. endo said the same
HE: They doā¦ until the epigenetic markers are lost with āageā
We are aging very differently. The therapies are presuming that you have receptors that can respond.
Now he comments on the post of the T nation guy i shared above:
He: Yes. The DNA is not directly affected; however, some genes are responsible for the epigenetic factors, and some for the repair and maintenance of healthy DNA. So those can lead to DNA damage, indirectly
When I attempt to explain the (generalized) problem using only epigenetics, it works like this: some damage is from missing cells. These failed the apoptosis test - they were grossly, obviously not right. The DNA, forced to copy by the AR boost, did not have enough epigenetic molecule groups of different types. So some DNA wasnāt at all transcribing right.
But, other cells were not so short-changed, in the marker proteins on top of DNA. Those cells were retained, but some of the genesā¦ especially long complex genes, and genes which work together to make something with many partsā¦ that sort of complexity is what Iām missing. Like, my skin doesnāt conduct electricity within it, laterally, so well. The simplest explanation is: gap junction proteins are missing (The guy developed sensitivity to electricity after PAS, interesting as hell.)
ME: Very valuable info
He: In another tissue, the blood brain barrier, there are analogous proteins, but they tie the inner and outer layer of the barrier together like a quilt. My BBB does not have so many of those, any longer. It can swell up from being near a lot of electricityā¦ after an airline flight, Iām a zombie, nearly. The wing is the worst, I think. itās all too much.
- I asked about the gene tests, especially the test @Gord did. It seems to me Gord found all the logical markers that why he got PFS.
Oftenā¦ far too oftenā¦ what they call a genetic test, is a test for gene product. They test for the transcribed proteinā¦ presuming that all genes transcribe perfectly. This is always a terrible error
Take a typical rare specific cancer. They know that certain genetic variants lead to a tissue wearing out earlier than for other people of the same age. They test for those genes - proper DNA base pair testing. What do they find? For most cancers of that type, the genes test perfectly fine: 60, 90 percent of cancers are NOT genetic.
Pretty near any genetic problem can also be caused by defective epigenetic markings on a perfectly good gene. So with the results above, I donāt think they are testing DNA. That seems more expensive than sampling for product. But because they know nothing about epigenetics, they are presuming that there are particular defective genes underlying specific patients problems.
Itās like imagine a building site with the different types of contractors, plumbing electrical plaster, etc. You need enough of each, in proportion. To get the ideal cell constructed. Now imagine that somebody hired three times as many plumbers, and one electrician. That cell is going to get built, but itās no good it Has to be torn down
That is when apoptosis comes along to remove the faulty cell, without it being necrotic. The case of my friends long bones, it was easy to see how the missing bone cells allowed his weight to crunch the other ones, like a wall of stone with cardboard stones stuck in among the real ones
ME: So maybe Accutane turned of some genes in my system then? Like maybe androgen receptor transcription on particular tissues etc.
Yes, the vitamin A sensitive tissues got such an overload. They mostly do these tests with rats, the system is analogous enough, that they can harm a juvenile rat and watch the progressI think what you see is the epithelial cell going from a specialized form, back to a more limited version of that same specialized form
Accutane and depression (He had this, not me)
The work of researchers which I read suggests that the initial major problem with depression and Accutane is caused by the blood brain barrier being breached and too much vitamin a getting through to the hippocampus. The cells of the hippocampus are always reproducing its extruding like a little tongue and the tip is dying off. So with the higher vitamin a dose, more cells reproduced in that generation, but Many of them were defective, and killed off by the bodyās natural process, apoptosis.
Intense dose of vitamin a and accelerates the trend towards the cells exhaustion, the point where itās structurally intact but like a factory that no longer produces as many different products or as many of them, itās comparatively inert to what it was.
Regarding depression and Accutane, I feel that this recent breakthrough is extremely relevant. After all, the skin of the blood brain barrier is epithelial, thatās where the retinoid receptors are.
I mostly feel that weāre just lost in time. The ways to understand us havenāt been written into textbooks yet. The pieces are there, the explanations of what happened to particular cells. But these are mechanisms without reversalā¦ itās going to take engineering crispr probes to restore missing methyl groups and other epigenetic markers.
One of the important things I learned in my reading is that we are inheriting damage to the marker proteins on our DNA. We are told that we pass on genes, but we can also pass on genes that arenāt going to be transcribed correctly.
Iām just saying, some of what Accutane made happen was built into my genes and on their surface already.
that Finasteride doesnāt damage some or much less than others is that it doesnāt cross the blood brain barrier as easily as it does in othersā¦