I think I've hacked it

[Swooping]

Okay, I explain a little more about castration:

Look, What is the role of castration? You take the balls out. Right? no testosterone anymore. So basically no DHT anymore. And no further miniaturization right. please read my writing as intelligently as possible. Miniaturization is DHT dependent. So you basically stop hair loss. No more DHT and testosterone binds the AR, so it can't get into the nucleus and drive miniaturization. But you're not inhibiting cytoplasmic AR, which, binds Beta-catenin either in presence of DHT or absence of DHt. Castration do not reduce AR expression levels. So, you won't see regrowth. Beta-catenin can't act in presence of AR. The binding of AR and beta-catenin is no completely DHT dependent. It's explained in the link I sent you.

So per your hypothesis you argue that AR expression increases over time. On what evidence do you base this? If this does happen then why is a compound like finasteride generally effective over many years? If AR expression would increase over time finasteride highly likely wouldn't provide such a long lasting effect. I don't see why a compound like finasteride would suddenly stop the increased AR expression from happening, I don't see in the first place why AR expression would get higher over time. Perhaps I'm missing something here though?

Secondly what experiment(s) led you to the notion that AR expression competes with b-catenin and can even render it inactive, can you give more information about these experiments? Or is this a known fact, if so could you pass me the literature?

Thanks. There is nothing wrong btw with hypothesizing, researching etc. It's only a good thing imo. It does however become stupid when one makes claims and then doesn't show up. We have seen enough of that stuff. Thanks.

[Swooping]

FGF11 - I appreciate all the work you are doing. Can you please address my question though. Why would AR issues cause balding in a pattern? Why would minoxidil be the BEST growth stimulator if the problem was purely AR? It doesn't add up. Dermarolling + Minoxidil are far better growth stimulators than Finasteride will ever be.

This might be of interest to you;

[FGF11]

So per your hypothesis you argue that AR expression increases over time. On what evidence do you base this? If this does happen then why is a compound like finasteride generally effective over many years? If AR expression would increase over time finasteride highly likely wouldn't provide such a long lasting effect. I don't see why a compound like finasteride would suddenly stop the increased AR expression from happening, I don't see in the first place why AR expression would get higher over time. Perhaps I'm missing something here though?

Secondly what experiment(s) led you to the notion that AR expression competes with b-catenin and can even render it inactive, can you give more information about these experiments? Or is this a known fact, if so could you pass me the literature?

Thanks. There is nothing wrong btw with hypothesizing, researching etc. It's only a good thing imo. It does however become stupid when one makes claims and then doesn't show up. We have seen enough of that stuff. Thanks.

Yes, AR expression increases overtime as hair follicle miniaturizes. Finasteride stops hair follicle miniaturization. Increased AR expression is the hallmark of male hair loss. Expression of the AR has also been found to be increased in balding scalp.


Finasteride is effective, as it stops gradual increase in AR expression, by stopping AGA from progressing and AR from getting activated, keeping AR levels normal. Increased AR expression is an AR dependent mechanisms. As AR is the driving force of AGA. So by catching hair loss early by taking finasteride, you stop gradual increase in the levels of AR. I hope this answers your first question. I leave the literature search on yourself.

As for the second question:

^ this is in AGA keratinocytes, levels of total beta-catenin has not changed, but levels of cytoplasmic beta-catenin in presence of DHT is negligible. This is done in AGA keratinocytes.

^ this is again in AGA keratinocytes.
First you can see that in presence and absence of DHT, AR receptor binds GSK-3beta ( a know regulator of beta-catenin).



read the figure, and take notice of the way beta-catenin and AR receptor acts differently in Keratinocytes of patients with AGA and normal keratinocytes. In normal patients, in presence of DHT both AR and Beta-catenin are in the cell nucleus. While, in patients with AGA, Beta-catenin can't get into nucleus. However, in presence of Wnt3A, the reverse happens. Note, that all the studies I am bringing here have been done in AGA compared with non-AGA (mostly in keratinocytes).

However, it is a completely known fact that AR and Beta-catenin antagonize in epithelial cells of mice.
[http://www.nature.com/jid/journal/v1...2015242a.html]

There about much more articles out there. Please read them carefully and if you are still not convinced let know.

[FGF11]

So per your hypothesis you argue that AR expression increases over time. On what evidence do you base this? If this does happen then why is a compound like finasteride generally effective over many years? If AR expression would increase over time finasteride highly likely wouldn't provide such a long lasting effect. I don't see why a compound like finasteride would suddenly stop the increased AR expression from happening, I don't see in the first place why AR expression would get higher over time. Perhaps I'm missing something here though?

Secondly what experiment(s) led you to the notion that AR expression competes with b-catenin and can even render it inactive, can you give more information about these experiments? Or is this a known fact, if so could you pass me the literature?

Thanks. There is nothing wrong btw with hypothesizing, researching etc. It's only a good thing imo. It does however become stupid when one makes claims and then doesn't show up. We have seen enough of that stuff. Thanks.

Tnx, the moment I feel that I am wrong, I have no shame of stating it. Also, I listened to Dr. Christiano interview which was posted here, you can see that they can't go ahead and test their compounds, because it is hard to do so. People should know that science is really hard and take time. Even for some one as recognized as her, it's incredibly hard to convince pharma to come and fund something that MIGHT have some effect. lol, let alone me. haha. So that's why I have decided to take things in my own hand. Also I'm up to some other stuff hair wise, that I'm not interested bringing them here for some reasons. She is a nice person though.

[FGF11]

ALSO, I would like you to notice the effect of LiCl, on beta catenin in presence of DHT, or maybe increased AR. I'm actually trying to be very careful, as not rising any false hope, all I'm saying is that this thing is much more effective (at least) than anything in the market, and the only reason it's not here, is because it is EXTREMELY expensive and EXTREMELY hard to deliver.

[FGF11]

Search this in google: "beta catenin androgen receptor interaction". I'm also going to not have access to here for a month or more.

[FGF11]

Search this in google: "beta catenin androgen receptor interaction". I'm also going to not have access to here for a month or more.

HAIRLOSS JUST SUCKS, I KNOW IT"S CHILDISH BUT I WISH EVERYONE COULD UNITE. There is no other way around this.

[Swooping]

Yes, AR expression increases overtime as hair follicle miniaturizes. Finasteride stops hair follicle miniaturization. Increased AR expression is the hallmark of male hair loss. Expression of the AR has also been found to be increased in balding scalp.


Finasteride is effective, as it stops gradual increase in AR expression, by stopping AGA from progressing and AR from getting activated, keeping AR levels normal. Increased AR expression is an AR dependent mechanisms. As AR is the driving force of AGA. So by catching hair loss early by taking finasteride, you stop gradual increase in the levels of AR. I hope this answers your first question. I leave the literature search on yourself.

Well I have read pretty much every study, so I know that there is evidence of higher AR expression in balding scalp (vertex, frontal) versus occipital. However to my knowledge, there is zero evidence that shows that AR expression increases over time during miniaturization, The studies that have been made show simply a static measurement where they take tissue from the scalp in a person and then they compare tissue from occipital to vertex or the front. I have never seen a study that suggests what you say, including the above. For that to happen they would need to follow-up subjects several years later from the first measurement. I would be very surprised if such a study exists.

I'll go over that other information one time later, quite busy at the moment. Will be following you though. Thanks anyway and I wish you good luck.

[youngin]

Well I have read pretty much every study, so I know that there is evidence of higher AR expression in balding scalp (vertex, frontal) versus occipital. However to my knowledge, there is zero evidence that shows that AR expression increases over time during miniaturization, The studies that have been made show simply a static measurement where they take tissue from the scalp in a person and then they compare tissue from occipital to vertex or the front. I have never seen a study that suggests what you say, including the above. For that to happen they would need to follow-up subjects several years later from the first measurement. I would be very surprised if such a study exists.

I'll go over that other information one time later, quite busy at the moment. Will be following you though. Thanks anyway and I wish you good luck.

The studies I see on AR expression or 5aR are always bald vs non-bald DP cells. Has no one investigated these expressions PRE balding? Just because its increased after balding doesn't make it the cause. Maybe external factors cause the change of expression.

If we hypothesize that AR expression is part of the problem that's fine, but why throw all of the other highly studied aspects out of the window? Has anyone felt the scalp of a NW7? I am NW6 and I can tell you that the vertex (earliest balding) of my scalp looks and feels like scar tissue. Do you think you can grow hair through scar tissue just with AR antagonists of sorts? Highly unlikely. My stance is that THIS is why dermarolling and minoxidil work.

By all means lets all figure this out but focusing on one single aspect is not doing anything new, especially with huge amounts of evidence based around immune issues and surrounding tissue.

[Swooping]

The studies I see on AR expression or 5aR are always bald vs non-bald DP cells. Has no one investigated these expressions PRE balding? Just because its increased after balding doesn't make it the cause. Maybe external factors cause the change of expression.

If we hypothesize that AR expression is part of the problem that's fine, but why throw all of the other highly studied aspects out of the window? Has anyone felt the scalp of a NW7? I am NW6 and I can tell you that the vertex (earliest balding) of my scalp looks and feels like scar tissue. Do you think you can grow hair through scar tissue just with AR antagonists of sorts? Highly unlikely. My stance is that THIS is why dermarolling and minoxidil work.

By all means lets all figure this out but focusing on one single aspect is not doing anything new, especially with huge amounts of evidence based around immune issues and surrounding tissue.

Well that's what I'm saying. FGF11 says that androgen receptor expression increases over time and that this results in miniaturization due to eventually AR competing with b-catenin. However like you mention evidence has never been shown that AR expression increases over time in balding scalp. What has been shown however in one measurement is that AR expression is higher in balding scalp in comparison to non-balding scalp. To my knowledge measurements have been never made pre-balding and after a while of balding to measure a possible increase of AR expression.

I'm not saying it's not possible, But evidence hasn't been shown yet for increase of AR expression over time in the balding scalp. At least not that I know? Maybe FGF11 does.

Also remember I don't hypothesize that AR expression is the problem, FGF11 does. I'm more in the camp of cell cycle arrest or senescence that relies on indicative evidence shown in papers by various researchers. That would be my line of thinking. Pure hypothetical thinking of me though, I don't make claims or project it as the truth.

You make a interesting point about fibrosis. Before I didn't think it was such problem in AGA. Simply because fibrosis is literally scarring and too much scarring will simply destroy the hair follicle, just as we see in cicatrial alopecia. Cicatrial (scarring) alopecia consists basically of fibrosis that leads to complete destruction of the hair follicle that is seen as irreversible. Until, one day maybe we are able to induce morphogenesis of hair follicles that could potentially fix the problem in something like cicatrial alopecia.

Guess I was wrong and you make a very good point, I do think fibrosis plays a role in (advanced) AGA. When we look at a study of Domyati(1.) for example;

In the frontal bald area of AGA, perifollicular fibrosis consisting of loose concentric layers of collagen was generally absent in 16 cases (40%) or mild in 14 cases (35%) in young age with mild AGA (Figure 2c). It was more marked, even with destruction of follicular structures, in the old age group with advanced AGA. The arrector pili muscle may be retained (Figure 2d). Perifollicular fibrosis showed highly significant correlation with both age of the patients (r = 0.78, P < 0.001) and correlated significantly with the severity of baldness (r = 0.46, P = 0.003). It showed significant inverse correlation with perifollicular inflammation (r = )0.31, P = 0.048). In normal controls, neither inflammatory infiltrate, apart from sparse perivascular infiltrate in a few biopsies, nor perifollicular fibrosis was observed in all studied specimens.

In the frontal (bald) area of AGA, perifollicular inflammatory infiltrate was observed in the majority of cases (90%). Meanwhile, no fibrosis was observed in 40% and only 10% showed marked fibrosis and complete destruction of hair follicles in the old age group with advanced AGA. These results are close to those observed by El-Domyati who reported inflammatory reaction in female subjects with AGA with destruction of follicular structure and replacement by fibrous tracts in severe cases. Meanwhile, Abell26 reported an inflammatory reaction in 75% of balding patients, focal fibrosis in 25%, and destruction of follicular structures in 5%.

Kligman25 demonstrated that perifollicular fibrosis was due to deposition of concentric layers of perifollicular collagen. The perifollicular fibrosis was evidenced by degranulation of follicular adventitial mast cells as well as enhanced collagen production by neighboring fibroblasts which resulted in 2- to 2.5-fold enlargement of the follicular dermal sheath.27

(The degranulation of mast cells should explain the PGD2 fanboys one possible explanation for increased PGD2 in scalp by the way. The largest amount of PGD2 is found in mast cells in the human body)

So I do believe fibrosis can become a problem and in some advanced cases even in AGA can cause destruction of the hair follicle, which would make AGA irreversible in some (very advanced) cases. Only creation of new hair follicles would help in this case.

That being said out of all the studies I would personally place my bet that AGA is simply premature senescence. Everything that happens correlates with senescence imo, including the inflammatory aspect of AGA. I hope this evidence towards senescence is completely wrong though, cause that would be f*cked up.

One thing is for sure imo, if you can make sure you take preventative measures. You might regret it later if you don't.




1. http://www.ncbi.nlm.nih.gov/pubmed/19527330)

[youngin]

Just to be clear I wasn't directing my last post at you Swoop, I was just piggy backing your quote. I agree with what you said. I am sure that cellular senescence is definitely involved, but this is a chain of events. Something like (CAUSE) -> Androgens -> Inflammation -> Fibrosis.. with the cause being still unknown or multi-factor. I think that calcium issues fit in this chain somewhere as well (Note BMP's affect on hair growth). I'll never forget reading the report about the doctor finding knitted calcification through the veins in the head of a bald cadaver. When you are as bald as me you can feel and see differences in the scalp.

[youngin]

A relevant hint about minoxidil:

Since collagen is the major product of fibroblast activity and lysyl hydroxylase catalyzes a crucial reaction in collagen biosynthesis, the combined effects of minoxidil offer the potential for its use as an antifibrotic agent. Thus, minoxidil may prove to be beneficial in treating skin conditions associated with collagen accumulation.

http://www.ncbi.nlm.nih.gov/pubmed/2826267

This is the strongest reasoning of why minoxidil works. It can reverse some fibrosis. Yet everyone tries to force some line of reasoning to make it align with androgen activity.

[FGF11]

Well I have read pretty much every study, so I know that there is evidence of higher AR expression in balding scalp (vertex, frontal) versus occipital. However to my knowledge, there is zero evidence that shows that AR expression increases over time during miniaturization, The studies that have been made show simply a static measurement where they take tissue from the scalp in a person and then they compare tissue from occipital to vertex or the front. I have never seen a study that suggests what you say, including the above. For that to happen they would need to follow-up subjects several years later from the first measurement. I would be very surprised if such a study exists

I'll go over that other information one time later, quite busy at the moment. Will be following you though. Thanks anyway and I wish you good luck.

Tnx, yes. No longitudinal studies have been done on AR expression during progression of AGA. However, studies haven been done on AR expression in presence of DHT. DHT induce AR expression. This basically equals a longitudinal study, and shows that if DHT not stopped, AR levels will increase.

[Ulti1]

A relevant hint about minoxidil:

http://www.ncbi.nlm.nih.gov/pubmed/2826267

This is the strongest reasoning of why minoxidil works. It can reverse some fibrosis. Yet everyone tries to force some line of reasoning to make it align with androgen activity.

Yeah I think fibrosis and calcium build up is a big problem. My scalp visually looks different and it's not the sebum. I had a crap ton of oil and sebum before I started losing hair and my scalp looked pearly white and healthy, it never flaked or caused build up..
Now my scalp looks like it's caked on with calcium or some shit.. I don't think it helps that my nails are so thick and made out of steel. I think I have too much calcium. No more milk for this guy.

[ShookOnes]

pretty sure tb 500 is the only thing legit besides fin minox atm.