I tried to create a thread but it has yet to be approved. Lemme tell you something, Dr. Alan Jacobs is a nice, guy, he’s a smart guy, but he don’t know jack sh!t about 5AR inhibition or why it causes long lasting effects. The problem is not any change in the androgen receptor structure, and if there is a change in the AR other than the reduction in AR quantity body wide, we should be looking at WHAT CAUSED THIS CHANGE. You wanna learn something? Read this.
I am reaching somewhat with the following hypothesis but wishful thinking is better than none at all, it is also a lot more complex than I currently comprehend but I’ve been living this for seven years and I am very perceptive to the situation. This theory fits real friggan well and would explain why we don’t recover, or do so very slowly. Also I am an accutane sufferer, but before you discount what I say, listen because what I have discovered may hold OUR future cure.
Both accutane and finasteride are 5AR inhibitors. Accutane by indirect competitive inhibition, and Finasteride by direct 5AR inhibition. 5AR is responsible for epithelial integrity. One of the problems I have consistently experienced after accutane is blood pressure spikes upon standing up after I have been laying down for a while, even a short time, feeling like I will pass out for a few seconds. This is happening almost every time I stand now. I have been taking a lot of vitamin D and was using the simplified methylation protocol to attempt to bring back rate of metabolism, so I have been pushing my sytem to respond - None of this matters yet but it will.
When I was searching for retinol uptake genes and RA synthesis/recycling genes, I found this blood pressue spike could be a problem of amyloid-beta plaque buildup as the result of reduced Transthyretin. Transthyretin is responsible for the transport of amyloid-beta protein so that it does not build up in the brain and lead to cognitive decline and eventually Alzheimer’s. Another one of the issues caused by buildup of Beta Amyloids is erectile dysfuntion. Here’s the kicker, TTR is also responsible for retinol and thyroxine transport into the brain.
Now what does this have to do with our favorite 5AR drugs? Transthyretin is produced in the choroid plexus epithelium of the brain. The epithelium of the entire body is modulated by 5 alpha reductase. If our brains suffered damage from accutane and during the process lost much of the ability to produce transthyretin, we lost the ability to transfer amyloid proteins, as well as not have the normal uptake of nutrients from the blood. That is a recipe for the problems we are experiencing. One of which is cognitive decline, different from brain fog but they are of the same nature. The damage from accutane would heal very slowly. Also with reduced TTR there would be a retinol uptake problem and therefore retinoic acid deficiency in parts of the brain. This would explain our loss of growth factors. When retinoic acid is not binding to CRABP2 and activating retinoic acid receptors, it is binding to FABP5 and activating kinase growth pathways like protein kinase B/ Akt. This is able to explain the decrease in Androgen Receptor quantity as the gh/igf1 axis and androgens are highly integrated. If the brain doesn’t have the necessary nutrients, it will not attempt to heal.
If you visit the “Significant Irreversible Hormonal Antagonism” section on max001.proboards, and go to ‘growth hormone igf1 axis’, you will find the following information on a study on rats -
“In rat pituitary GH3 cells, Retinoic acid <1 microM stimulated growth hormone secretion by 220%. 50 nM HCT stimulated GH secretion 3,5 times and in synergy GH secretion was stimulated seven times”
=======================================================================
I still experience dry skin and scalp, with my worse problems being low energy and libido as well as some level of cognitive decline and as I try and fix my problems almost consistent brain fog and spikes in blood pressure when I stand from laydown. Loss of epithelial integrity means less endogenous transthyretin production in the choroid plexus and decreased nutrient uptake to the brain. This may be the origin of our problems and is the first palpable common ground between finasteride and accutane.
I wrote the above message for accutane sufferers. But the idea is still the same. Both of us have suffered damage to epithelium body wide. This means in the brain as well. If we have all lost the ability to produce transthyretin, this creates a loop where the brain will not heal as it does not receive the nutrients from the blood. TTR is responsible for transfer of retinol into the brain for conversion to retinoic acid. RA is needed for the differentiation of highly specific neuronal cells. Therefore the rate of recovery will be extremely slow if there is a deficiency here. You cannot test this with a standard retinol test. If you still have dry skin, you should realize there is a problem. I took accutane 7 years ago at the age of 15.5, and I still have dry skin and scalp, almost every day. The sooner this gets fixed the sooner we recover epithelial integrity of the brain and entire body. The reason our androgen receptor quantity is low, is because with damaged pathways of the CNS and reduction of neurosteroids, the brain cannot recover. This is why we are suffering.
Forget the research on androgen receptor structure, there is nothing that has changed that is not attributed to the damage that has occurred in our brains, along the pathways that are sensitive to 5AR. When this is eventually realized, that’s when I will donate my money. Our cure may be of the same origin, but you guys are taking it step by step and it’s going way too fucking slow. Hopefully you will see where I am coming from and if you agree we can start working together. This is information that should be relayed to the men who are holding the roundtable meeting this february, they make be able to make gigantic strides if I am right about this.