https://www.sciencedirect.com/science/article/abs/pii/S0960076017301024
http://www.associazionevittimefinas...oads/2017/05/Melcangi-Research-April-2017.pdf
These studies were very interesting to me. Basically showing that in CSF in post finasteride people, there is low 17 estradiol, progesterone, pregnenolone, and low DHT.
As we know blood tests for this hormones are ok, but CSF shows a lot more how they work and what is happening.
In the second study, Melcangi assume that it is obvious AR receptor overexpression going on. Which as we know also was confirmed by Italian study on post Finasteride patients.
Some people confuse AR overexpression with the strong steroid action. in the cell, you have ARs on the outside of the cell, then ARs get phosphorylated and move into the center of the cell, when they bind to ARE using ZINC finger motif
SO cell can have overexpressed number of ARs ( so called little trains which carry stuff into the center of the cell) . And then body fight this, and it either loses ZINC finger, not to bind them to ARE, or it methylates DNA. So the signal is simply silenced.
SO increasing density or number of AR is not what you want in this situation.
Ok, now lets return back to the studies. As I looked a these studies. we see that DHT, 17 estradiol , progesterone , pregnenolone are low in CSF. means that these stupid ARs bind then excessively and then just waste them since they cant create a signal. Those little trains bind carry those hormones into the center of the cell, bind, or dont even bind ( if zinc finger is lost ) and then if DNA Is overmethylated signal for gene expression is just muted.
Now if you look at these hormones, 17 Estadiol, DHT, pregnenolone. progesterone. Those are the hormones that fin effected as progestin.
Since when you give progestin, it lowers progesterone production. That is one. If you give progestin what it does? It binds NADPH, just like progesterone does. but it does not do anything . it just binds it and wastes it.
All these hormones were made with NADPH. like pregnenolone. like 17 beta estadiol. like DHT. are made with NADPH.
And since fin was binding NADPH all this time. then all these hormones were low. Cortisol also could be one of them. I dont know why they did not mention it in the study.
So the body overexpressed all their receptors not just DHT. Overexpressed means that there are many receptors in the cell. It does not mean the action is strong).
Now, which receptors are overexpressed. So basically estrogen receptor. progesterone, AR, probably cortisol. and the interesting thing is pregnenolone.
Pregnenolone binds and controls CB1 cb2 receptor. Cannabinoid receptor. That receptor is super important in controlling immune function. and LH. basically thru that receptor
estrogen inhibits LH.
Plus the emotional problems could stem from that receptor along with problems in not enjoying or feeling anything at all. Anhedonia etc.
Pregnenolone usually controls that receptor, it even is used to block action of THC( marijuanna)
a lot of people try to replace all these hormones, Some one takes progesterone, another one pregnenolone, another one, estrogen , another one DHT.
But these hormones, upregulate each other. Meaning that if you take progesterone, you will upregulate number of Rs for estrogen, and DHT. etc.
If you take estrogen this will upregulate progesterone, and estrogen
Regulation of estrogen receptor α and progesterone receptor (isoform A and B) expression in cultured human endometrial cells — University of Texas Southwestern Medical Center
You see in this study , estrogen could not downregulate its receptors alone. but with progesterone together, both were downregulated. by downregulated I mean the expression of these little trains, which carry something into the center of the cell. for binding to AREs.
I wonder if this all taken together( the hormones which are low in CSF) , could downregulate numbers of all those trains, and then upon withdrawal from taking hormones.. the body will turn off Methylation mechanism, which is silencing the genes now, and will retain zinc to bind THE ANDROGEN RECEPTORS, OR ESTROGEN RECEPTORS to the AREs.
As a side note. Anavar was suggested solely for this reason. anavar has very high anabolic ratio. and very low androgenic. It should not even bind to androgen receptor at all. but it does. same as stanozolol ( which is also very anabolic)) and it causes a rapid cytosolic depletion of ARs. but provides no androgenic action depleting them. And thus the body could demethylate the DNA and increase the zinc finger.
Anabolic steroids are synthetic derivatives of testosterone and are characterized by their ability to cause nitrogen retention and positive protein metabolism, thereby leading to increased protein synthesis and muscle mass. There are disagreements in the literature in regards to the interaction of anabolic steroids with the androgen receptor (AR) as revealed by competitive ligand binding assays in vitro using cytosolic preparations from prostate and skeletal muscle. By use of tissue extracts, it has been shown that some anabolic steroids have binding affinities for the AR that are higher than that of the natural androgen testosterone, while others such as stanozolol and methanedienone have significantly lower affinities as compared with testosterone. In this study we show that stanozolol and methanedienone are low affinity ligands of the rat recombinant AR as revealed by a ligand binding assay in vitro, however, based on a cell-based AR-dependent transactivation assay, they are potent activators of the AR. We also show that a single injection of stanozolol and methanedienone causes a rapid cytosolic depletion of AR in rat skeletal muscle.
Based on these results, we conclude that anabolic steroids with low affinity to AR in vitro, can in fact in vivo act on the AR to cause biological responses.
Unfortunately , the reason why it did not work for a lot of people could be too short of a cycle. or since there are alot more connected hormones are overexpressed at the same time. and they could not allow single manipulations to stick. Like as we saw from that study with estrogen, if progesterone was not given , estrogen could not downregulate even its own action( it does not stick) that is why people like
@Jack17 Cycle progesterone, feels cured, and then it comes back in a while.
this is why I mentioned from the start that good cycle could be testosterone with progesterone, ( it takes care of estrogen, dht, and progesterone found low in CSF)
So now, we know that FIN did all this with binding NADPH. and most these hormones ( low in the study) would be effected by NADPH. except progesterone. since fin as a progestin. effected that directly.
B1 increases NADPH. And forces all the hormones that fin was inhibiting up. and this will downregulate them. This is what happened to me. I had insane crazy hair grows after b1. All over the place. The hair doubled on my body.
B2 on another hand. Is the most important vitamin in demethylating enzymes. which are silencing all these hormones now. and . I get reports of people getting much better on B2.
@Troy
So the outcome of this all, we need to concentrate on Cb1 receptor. AR, ER, PR.
As the study above shows that if you give them by connected couples that does downregulate the expression of their Receptors( little trains.) and then when you come off. you will have much less ARs and body will have to turn off the silencing mechanism.
Or the second way is to turn off the silencing mechanism from the start by trying to demethylate the DNA.
@zadig777
I think this is might be ( just a guess) how urine could work. and works for people. Since you feed all these hormones that have overexpressed receptor. And on the snap back you feel better. But this route is a guess. we dont know what urine does. at the same time. Urine could have all those hormone, in proper rations. and by feeding them back , you get better on the snap back/
So as you can see it is silly to focus just on androgen receptor here, it is the whole system of steroids got fucked.
This is why so much time has passed and people did not really get cured. And if cured I am sure they have some lingering symptoms. since they did not account for all the systems affected by fin. which are highly interconnected. they think FIN inhibits 5AR. Fin as a progestin JUST binds NADPH. and inhibits tons of places.
Lets discuss this, and address every possibility how to fix it.
We do have TEI, ( which is in my mind takes care of all these, since they balance minerals, and dont look how you feel,, , we have urine which could be just a perfect cure in this case.( I guess needs to be cycled, not drank all the time) in this case.
We can attempt to address the hormones missing in the CSF according to this study. Address Cb1 receptor at the same time.
I think it gives us a lot better understanding why stuff did not stick before
This is why my suggestions were testosterone with progesterone. or testosterone with the thyroid. Or testosterone with anavar. And it has nothing to do with any low test states LOL
but you can easily try to replace all these low hormones mentioned above.
and try to cycle estrogen plus progesterone plus pregnenolone plus dht
Or we can come up to the solution how to use high dose B vitamins for this,.
@Troy
Also we might think about feeding the testosterone plus DHEA as a second variant which were high in CSF . May be body is doing something with those.
Also another note about progesterone. If fin is progesterone, then may be it downregulated the PR receptor. WE have to consider this possibility also
