I think I've hacked it

[trunks]

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.

Really interesting

Regarding another possible Minoxidil effect on AGA:
Minoxidil may suppress androgen receptor-related functions

We hypothesized that minoxidil may influence the AR or its downstream signaling. These tests revealed that minoxidil suppressed AR-related functions, decreasing AR transcriptional activity in reporter assays, reducing expression of AR targets at the protein level, and suppressing AR-positive LNCaP cell growth. Dissecting the underlying mechanisms, we found that minoxidil interfered with AR-peptide, AR-coregulator, and AR N/C-terminal interactions, as well as AR protein stability. Furthermore, a crystallographic analysis using the AR ligand-binding domain (LBD) revealed direct binding of minoxidil to the AR in a minoxidil-AR-LBD co-crystal model, and surface plasmon resonance assays demonstrated that minoxidil directly bound the AR with a Kd value of 2.6 μM. Minoxidil also suppressed AR-responsive reporter activity and decreased AR protein stability in human hair dermal papilla cells. The current findings provide evidence that minoxidil could be used to treat both cancer and age-related disease, and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related diseases

Maybe this feature makes Minoxidil effectibe on early AGA?

[UNBEAT]

I have oily scalp too, with to much sebum that creates flakes and hair loss with plugs. Do you think that minoxidil can help

[Swooping]

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.

I get what you mean although I think everything starts with Androgens > AR. So it starts from the microenvironment imo. The whole process is definitely intriguing though.

Do you have some literature to read about the stuff you mention? I would be interested, thanks.

[UNBEAT]

Any news from fgf11?

[youngin]

I get what you mean although I think everything starts with Androgens > AR. So it starts from the microenvironment imo. The whole process is definitely intriguing though.

Do you have some literature to read about the stuff you mention? I would be interested, thanks.

Here is the article I was talking about at the end of my post: http://jama.jamanetwork.com/article....ticleid=256511

This guy has a similar idea (http://www.evolutionary.org/forums/a...pic-28623.html) though I don't agree with everything said. He even quotes some articles that correlate steroid usage (higher test) to calcification.

[youngin]

Swoop,

Look at this interesting study as well: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639964/ Mechanical stress could be how AGA starts.

[Chemical]

Swoop,

Look at this interesting study as well: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639964/ Mechanical stress could be how AGA starts.

I've read that study and thought it was quite interesting so I'm going to add something to the discussion.

I think you should be careful of confirmation bias because you'll only find what you want to believe, you might even turn a blind eye to some facts so I'd wholeheartedly suggest keeping an open mind. I say this from personal experience.

Fir clarification, the study does suggest "mechanical stress" in the title but they dont actually mean that, heres what they say in their results/discussion:

The involuntary tonic contraction of occipitofrontalis muscle is related to psychological stress conditions,[23] facial expression,[24] the maintenance of visual field,[19] and an aponeurotic tension model of human craniofacial growth,[25] so the galea aponeurotica supports a continuous stress which is transmitted to ECM and cells of each tissue, dermal papilla, and dermal sheath cells included. The deformation energy does not cause apparent damage to scalp skin, but its interplay with androgens could be fatal in organ remodeling of hair follicles. This androgen-mediated molecular response to mechanical stimulation can play the anabolic role instead of biological virilization role, as it has been extensively studied in tissues whose function is closely linked to the physical force support.[26] Furthermore, it has been reported that TGFβ-1 increases the expression of Hic-5 in hypertrophic scars fibroblasts[27] and it potentiates AR transactivity in balding dermal papilla cells[28] by autocrine loop [Figure 3]. Hence, the long-lasting cyclic strain would cause a slow, chronic, and progressive environmental adaptation process in balding hair follicles since puberty.

They've said here that the mechanical stresses are a combination of muscular tension from stress, facial expressions, and the eye movements. what? Thats a bizarre finding. However, thats not the conclusion!

They propose the idea that this muscular stress causes an increase in anabolism. Like when you train your biceps, AR expression gets increased and local IGF-1R gets upregulated as a result of the environmental stressors. Thats why working out makes your muscles bigger.

So this increase in AR activity increases TGF-Beta1 (via DPC), which then increases Hic-5, and Hic-5 potentiates AR activity in DPC leading to a closed positive feedback. According to their theory.

This is quite interesting because TGF-Beta is known to inhibit hair growth in a paracrine manner, but it also causes fibrosis when overexpressed - like you've been going on about!

In many diseases, excessive TGF-beta contributes to a pathologic excess of tissue fibrosis that compromises normal organ function, a topic that has been the subject of numerous reviews [1-3]

Furthermore:

Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth.

R1881 stimulated the growth of KCs by 41% when cocultured with beard DPCs (Fig. 3A, lane 1 vs. 2). In contrast, R1881 decreased the growth of KCs by 50% in the coculture with DPCs from AGA (Fig. 3A, lane 3 vs. 4). R1881 showed no significant effect on the growth of KCs cocultured with either nonbald frontal or occipital DPCs (Fig. 3A, lane 5 vs. 6 and lane 7 vs. 8).

I'd recommend reading the full pdf, its got some revealing insights.

R1881 is an AR agonist. When the balding hair follicles were co-cultured with keratinocytes, they had reduced proliferation. In contrast, beard hair follicles stimulated KC growth (via paracrine IGF-1). The balding hair follicles secreted TGF-Beta1 when stimulated with the AR agonist.

The concentration of total TGF-β1 in the conditioned medium treated with 10–9 M R1881 was increased by 2.68-fold compared with the control (Fig. 5, lanes 1 and 2). Anti-androgen CPA at the concentration of 10–6 M completely diminished this increase, demonstrating that the androgen-AR system is involved in the induction of TGF-β1 (Fig. 5, lane 3). Moreover, the concentration of active TGF-β1 was 174.1 pg/ml in the medium treated with 10–9 M R1881, whereas it was 12.9 pg/ml in the medium treated with ethanol (Fig. 5, lanes 4 and 5). Likewise, this induction of active TGF-β1 was reversed by 10–6M CPA (Fig. 5, lane 6). From these results, the TGF-β1 activity is regulated by androgens through both its production and activation. When DPCs from the nonbald frontal scalp were cocultured with KCs, 10–9 M R1881 did not show any significant effect on the concentration of total and active TGF-β1 in the conditioned medium (Fig. 5, lanes 7–10).

So you can see that the AR is the main mediator of this cascading chain. By blocking AR you can prevent the TGF-Beta1 induced fibrosis. Skin is not a fixed organ. Its constantly renewing, just like hair. The hair doesnt grow at the tips, it grows at the root, it starts bottom. Skin does the same. If TGF-Beta stops signalling to nearby DPC/KC and fibroblasts then the skin can turnover the fibrosis as it sheds the layers. But if TGF-Beta is present then you'll constantly have fibrosis present. Your theory is spot on, but the cause is AR like FGF11 and swoop have been talking about.

I hope this has shed some light on this topic.

[youngin]

I like the civil conversation we are having and exchanging ideas. I don't have much time to respond right now but I have to say Chemical I don't think you can do anything with AR and reverse fibrosis and calcification of surrounding tissue. It's very likely AR is part of the cause but once fibrosis sets in I believe you are stuck without minoxidil which basically removes it to an extent, and manual wounding. This is exactly why castration doesn't regrow all hair.

[Swooping]

Thank guys very interesting things mentioned here.

@youngin, thanks will be going over that literature soon and will respond after .

[youngin]

I think this study is very clearly explained.

They've said here that the mechanical stresses are a combination of muscular tension from stress, facial expressions, and the eye movements. what? Thats a bizarre finding. However, thats not the conclusion!

This is not bizarre at all. I'm not sure if you really understood what they were pointing out. Psychological stressors can become physical, like stress causing jaw tension, brow movement, etc. These use muscles that move and tighten the galea, which then causes mechanical stress on the follicle cells causing a cascade of Hic-5 -> AR -> inflammation -> fibrosis. This is not unusual as many cells in our body respond to mechanical stress (see bones).

So you can see that the AR is the main mediator of this cascading chain. By blocking AR you can prevent the TGF-Beta1 induced fibrosis. Skin is not a fixed organ. Its constantly renewing, just like hair. The hair doesnt grow at the tips, it grows at the root, it starts bottom. Skin does the same. If TGF-Beta stops signalling to nearby DPC/KC and fibroblasts then the skin can turnover the fibrosis as it sheds the layers. But if TGF-Beta is present then you'll constantly have fibrosis present. Your theory is spot on, but the cause is AR like FGF11 and swoop have been talking about.

I have to disagree. When I speak about cause I do not mean a single link in a chain, I am speaking about ROOT cause. In this case AR is not the root cause, mechanical stress would be if such a hypothesis were correct. If this could be definitively proven (I'm not saying it is) then would you treat AR as the cause or the tension problem?? It's interesting that the Botox study gets ignored even though the author has been open about it as well.

http://journals.lww.com/plasreconsurg/Fulltext/2010/11000/Treatment_of_Male_Pattern_Baldness_with_Botulinum.79.aspx

[Chemical]

I think this study is very clearly explained.

This is not bizarre at all. I'm not sure if you really understood what they were pointing out. Psychological stressors can become physical, like stress causing jaw tension, brow movement, etc. These use muscles that move and tighten the galea, which then causes mechanical stress on the follicle cells causing a cascade of Hic-5 -> AR -> inflammation -> fibrosis. This is not unusual as many cells in our body respond to mechanical stress (see bones).

I didnt explain myself properly, sorry. They mentioned physiological factors that everyone is likely to experience at some point in their life. The kinds of stress they are talking about dont seem to be extreme enough like working out or gravity (bone mechanosensitivity). This involuntary natural movement of muscles without any form of resistance shouldnt warrant an increase in anabolism. In the case of bone, normal muscular movements and activity does not automatically lead to osteoblastogenesis, theres a cellular threshold. Thats why people in space use resistance training to keep mineral bone density high. The same principles apply to muscle. You can't cause muscle to grow by just moving it without resistance. This is whats baffling me.

They were specifically referring to the muscle in the forehead region:

The involuntary tonic contraction of occipitofrontalis muscle

The hairs themselves are designed to withstand tugging and mechanical pulling forces, but excessive traction can lead to hairloss. They're suggesting the occipitofrontalis muscle is increasing local androgen sensitivity. That's something I dont understand. Hic-5 activation is controlled by forces action on the cytoskeleton. DHT is known to increase the expansion of the skull so maybe that triggers Hic-5 indirectly leading to increased anabolism?.

Interestingly, a triggering stimulus that can alter the inactive standby status of Hic-5 is the deformation of the cytoskeleton by physical forces;[15,16] therefore, mechanical stimulation can promote overexpression of molecular signals implicated in AGA pathogenesis.

Furthermore:

Regardless the pattern or degree of severity, AGA is always limited to the skin overlying the galea aponeurotica. This is a thin and relatively inelastic tendon-like tissue sheet that communicates the frontal and occipital bellies of occipitofrontalis muscle.[17] Balding scalp skin is firmly bounded to galea by fibrous rigid subcutaneous layer, so elastic deformation affecting the galea is shared by the three upper layers as a structural unit[18] [Figure 1], whereas the remaining scalp skin freely slides over deeper layer, with low strain transmission to hair follicles and unaffected by AGA.

The pattern that AGA manifests is linked to the region they are talking about. Their model/simulation isnt too conclusive but I think its a valid hypothesis.

Addressing your point about fibrosis:

I don't think you can do anything with AR and reverse fibrosis and calcification of surrounding tissue. It's very likely AR is part of the cause but once fibrosis sets in I believe you are stuck without minoxidil which basically removes it to an extent, and manual wounding. This is exactly why castration doesn't regrow all hair.

It appears fibrosis isnt permanent as one might expect. Fibrosis can be reduced, but it doesnt happen with a magic drug. Minoxidil actually cant reverse fibrosis the way you think it does. It doesnt break down fibrotic tissue. But in the presence of minoxidil, fibroblasts cannot create fibrotic tissue properly. Look at this study:

Minoxidil exerts different inhibitory effects on gene expression of lysyl hydroxylase 1, 2, and 3: implications for collagen cross-linking and treatment of fibrosis.

Abstract
Collagen deposits in fibrotic lesions often display elevated levels of hydroxyallysine (pyridinoline) cross-links. The relation between the occurrence of pyridinoline cross-links and the irreversibility of fibrosis suggests that these cross-links contribute to the aberrant accumulation of collagen. Based on its inhibitory effect on lysyl hydroxylase activity minoxidil has been postulated to possess anti-fibrotic properties by limiting the hydroxylysine supply for hydroxyallysine cross-linking. However, to interfere with hydroxyallysine cross-linking specifically lysyl hydroxylation of the collagen telopeptide should be inhibited, a reaction predominantly catalysed by lysyl hydroxylase (LH) 2b. In this study, we demonstrate that minoxidil treatment of cultured fibroblasts reduces LH1>>LH2b>LH3 mRNA levels dose-and time-dependently, but has essentially no effect on the total number of pyridinoline cross-links in the collagen matrix. Still the collagen produced in the presence of minoxidil displays some remarkable features: hydroxylation of triple helical lysine residues is reduced to 50% and lysylpyridinoline cross-linking is increased at the expense of hydroxylysylpyridinoline cross-linking. These observations can be explained by our finding that LH1 mRNA levels are the most sensitive to minoxidil treatment, corroborating that LH1 has a preference for triple helical lysine residues as substrate. In addition, the non-proportional increase in cross-links (20-fold) with respect to the decrease in lysyl hydroxylation state of the triple helix (2-fold) even suggests that LH1 preferentially hydroxylates triple helical lysine residues at the cross-link positions. We conclude that minoxidil is unlikely to serve as an anti-fibroticum, but confers features to the collagen matrix, which provide insight into the substrate specificity of LH1.

This study also confirms minoxidils rate limiting effect on fibrosis generation.

The fibrotic chains/links are heavily blunted due to minoxidil, somehow the fibroblasts are unable to create new fibrotic deposits in the ECM. The existing fibrosis is not affected.

However, according to this study, fibrosis isnt permanent and is reversible:

A Peptide Derived from Endostatin Ameliorates Organ Fibrosis

To assess whether endostatin peptides could reverse fibrosis that was already present, we injected E4 into human skin 2 days after a single TGF-β administration, when dermal thickness was already evident (fig. S3, A and B; P = 0.045, TGF-β versus vehicle). Similar to human skin cotreated with E4 and TGF-β, delayed E4 administration also significantly ameliorated TGF-β–induced dermal fibrosis (Fig. 2, E and F). Our findings indicate that the C-terminal peptide of endostatin can prevent the development and progression of fibrosis and can also reverse TGF-β–induced fibrosis in human skin.

The N-terminal peptide of endostatin has been reported to ameliorate peritoneal sclerosis by reducing expression of TGF-β and α-SMA (31). Neutralization of endostatin exaggerated tissue remodeling and interstitial fibrosis with increased tissue collagen and MMP-2 and MMP-9 activities in a rat myocardial infarction model (34). These reports suggest that endostatin might interact with some profibrotic factors in fibroproliferative circumstances. In our experiments, E3 and E4 reduced dermal thickness of mouse and human skin treated with TGF-β and also inhibited bleomycin-induced skin and lung fibrosis. This suggests that the antifibrotic effect of the endostatin C-terminal peptide may be due, in part, to its blockade of TGF-β activity.

I would encourage you read to read the full pdf.

Inhibition of TGF-Beta causes the reversal of fibrosis. Which means fibrosis is only present so long as an agent is promoting it. Once you remove the stimulus, it cant sustain itself. AR -> TGF-Beta. You silence AR and you prevent the rise in TGF-Beta. A reduction in TGF-Beta as the study has pointed out, leads to a gradual decrease in fibrotic tissue in ECM.

I have to disagree. When I speak about cause I do not mean a single link in a chain, I am speaking about ROOT cause. In this case AR is not the root cause, mechanical stress would be if such a hypothesis were correct. If this could be definitively proven (I'm not saying it is) then would you treat AR as the cause or the tension problem?? It's interesting that the Botox study gets ignored even though the author has been open about it as well.
http://journals.lww.com/plasreconsur...ulinum.79.aspx

That botox study is a good find, and once again it ties in with AR as per the authors conclusions. Botox increases HIF-1/VEGF and I've covered the hair growth promotive effects of this pathway over in my thread.

Mechanistically, the scalp behaves like a drum skin with tensioning muscles around the periphery. These muscle groups—the frontalis, occipitalis, and periauricular muscles and to a minor degree the temporalis—can create a “tight” scalp when chronically active. Because the blood supply to the scalp enters through the periphery, a reduction in blood flow would be most apparent at the distal ends of the vessels, specifically, the vertex and frontal peaks. Areas of the scalp with sparse hair growth have been shown to be relatively hypoxic, have slow capillary refill, and to have high levels of dihydrotestosterone.4Conceptually, Botox “loosens” the scalp, reducing pressure on the perforating vasculature, thereby increasing blood flow and oxygen concentration. The enzymatic conversion of testosterone to dihydrotestosterone is oxygen dependent. In low-oxygen environments, the conversion of testosterone to dihydrotestosterone is favored; whereas in high-oxygen environments, more testosterone is converted to estradiol.4

Is it mere coincidence that the AR is implicated in nearly every study relating to hairloss (both directly and indirectly)? I'm a rational person, I believe things that have correlation and justifiable/rational causative mechanisms.

The elusive root cause that you are referring to is the genetic component. Unless you can use epigenetics or gene targeting, its a hopeless endeavor. AR is the biggest factor that mediates the genetic predisposition to AGA. If you get rid of the strongest link in the chain, the rest of the chain becomes useless, this is why targeting the AR pathway is so efficient. By taking down one pathway you automatically cancel out the rest, thats a much easier task than trying to shutdown genes(?). I understand if you disagree, but what do you reckon the root cause might be besides the AR? The mechanical stress aggravates AR induced hairloss, this is quite clear, so that theory is out the window. The only other theory people have postulated are PGD2 and autoimmunity which I'm not sold on.

[youngin]

I didnt explain myself properly, sorry. They mentioned physiological factors that everyone is likely to experience at some point in their life. The kinds of stress they are talking about dont seem to be extreme enough like working out or gravity (bone mechanosensitivity). This involuntary natural movement of muscles without any form of resistance shouldnt warrant an increase in anabolism.

This is not quite true. You do not have to do resistance training to grow muscle. This happens quite naturally for a man going into his teenage years. Also, you cant say there is no resistance in these forehead muscle movement either. Muscle and skull growth changed quite obviously through male puberty.

In the case of bone, normal muscular movements and activity does not automatically lead to osteoblastogenesis, theres a cellular threshold. Thats why people in space use resistance training to keep mineral bone density high. The same principles apply to muscle. You can't cause muscle to grow by just moving it without resistance. This is whats baffling me.

Actually the point I was making was not about osteoblastogensis, it was about cellular structure changes and signalling because of mechanical stress. As seen in the book "The Body Electric" bones actually even emit different electrical signaling when under tension.

The hairs themselves are designed to withstand tugging and mechanical pulling forces, but excessive traction can lead to hairloss. They're suggesting the occipitofrontalis muscle is increasing local androgen sensitivity. That's something I dont understand. Hic-5 activation is controlled by forces action on the cytoskeleton. DHT is known to increase the expansion of the skull so maybe that triggers Hic-5 indirectly leading to increased anabolism?.

You may need to re-read the study again to understand what they are saying about mechanical stress. I do not see anything being linked directly to the occipital muscles besides that being the source of force.

It appears fibrosis isnt permanent as one might expect. Fibrosis can be reduced, but it doesnt happen with a magic drug. Minoxidil actually cant reverse fibrosis the way you think it does. It doesnt break down fibrotic tissue. But in the presence of minoxidil, fibroblasts cannot create fibrotic tissue properly. Look at this study: The fibrotic chains/links are heavily blunted due to minoxidil, somehow the fibroblasts are unable to create new fibrotic deposits in the ECM. The existing fibrosis is not affected.

Yes. I mistakenly said "reverses" thought I did not mean it literally. It blunts collagen formation and probably calcification while your cells recycle as per usual. The dermarolling probably speeds this up with wounding and prompting repair of the skin cells, while minoxidil is stopping the fibrosis from happening during repair.

That botox study is a good find, and once again it ties in with AR as per the authors conclusions. Botox increases HIF-1/VEGF and I've covered the hair growth promotive effects of this pathway over in my thread.

I think this is another stretch. Science is very aware of what VEGF is used for and it does not have a strong link to AR. It has a strong link to vascular modeling. This is not just a side function, this is the MAIN function. We can't make these pieces of the puzzle fit to our own agenda.

Is it mere coincidence that the AR is implicated in nearly every study relating to hairloss (both directly and indirectly)? I'm a rational person, I believe things that have correlation and justifiable/rational causative mechanisms.

It's not a coincidence, it definitely is a link in the chain. MOST studies MUST agree AGA is caused by AR from the outset and this is the focus, they do not focus on other pathways. So its not really a coincidence if you are targeting a specific pathway.

The elusive root cause that you are referring to is the genetic component. Unless you can use epigenetics or gene targeting, its a hopeless endeavor.

No one has discovered the root cause, thats why we have these hypothesis. PGD2 and immunity are probably downstream of androgen activity in the chain. It maybe multi-factor epigenetic. The monozygotic twin studies show that it IS a factor.

[Chemical]

This is not quite true. You do not have to do resistance training to grow muscle. This happens quite naturally for a man going into his teenage years. Also, you cant say there is no resistance in these forehead muscle movement either. Muscle and skull growth changed quite obviously through male puberty.

The changes that happen during puberty are a result of pubertal HGH/IGF-1 spikes. Although this is deviating considerably from the point I was making about force/stress induced anabolism. I think the resistance from tendons and skin is not enough to promote an anabolic reaction, this is my point.

Actually the point I was making was not about osteoblastogensis, it was about cellular structure changes and signalling because of mechanical stress. As seen in the book "The Body Electric" bones actually even emit different electrical signaling when under tension.

Structural changes as a result of environental stresses is a general statement. We are talking about an increase in anabolism (AR upregulation is an anabolic reaction), hence my reference to osteoblastogenesis. Under compressional forces bone tries to increase osteoblastogenesis - which requires calcium/phosphate. In the case of deficiency in calcium/phosphate/D3, bone deformation will occur. What I'm trying to say is that the body favours anabolism when counteracting environmental stressors it cant handle. I guess it is possible for AGA predisposed frontal hair to react to environmental stresses and upregulate AR.

You may need to re-read the study again to understand what they are saying about mechanical stress. I do not see anything being linked directly to the occipital muscles besides that being the source of force.

Their theory is that mechanical stimulation upregulates Hic-5, which in turn activates AR -> TGF-Beta. I'm not missing something am I?

Interestingly, a triggering stimulus that can alter the inactive standby status of Hic-5 is the deformation of the cytoskeleton by physical forces;[15,16] therefore, mechanical stimulation can promote overexpression of molecular signals implicated in AGA pathogenesis.

Tell me what you understand by their statement on involuntary muscle contraction. I've given you my opinion on this topic, I'd like to see yours with a bit more justification. The goal is for me to understand your point.

Yes. I mistakenly said "reverses" thought I did not mean it literally. It blunts collagen formation and probably calcification while your cells recycle as per usual. The dermarolling probably speeds this up with wounding and prompting repair of the skin cells, while minoxidil is stopping the fibrosis from happening during repair.

Do you also agree that TGF-Beta reduction via inhibition of AR can reverse fibrosis?

I think this is another stretch. Science is very aware of what VEGF is used for and it does not have a strong link to AR. It has a strong link to vascular modeling. This is not just a side function, this is the MAIN function. We can't make these pieces of the puzzle fit to our own agenda.

When talking about AR and botox relationship I got it from this paragraph in the botox study: They tied Botox to AR, I simply brought their point up to illustrate how AR is so frequently implicated in AR. I proposed a different mechanism for Botox's hair growth promoting effects.

Mechanistically, the scalp behaves like a drum skin with tensioning muscles around the periphery. These muscle groups—the frontalis, occipitalis, and periauricular muscles and to a minor degree the temporalis—can create a “tight” scalp when chronically active. Because the blood supply to the scalp enters through the periphery, a reduction in blood flow would be most apparent at the distal ends of the vessels, specifically, the vertex and frontal peaks. Areas of the scalp with sparse hair growth have been shown to be relatively hypoxic, have slow capillary refill, and to have high levels of dihydrotestosterone.4Conceptually, Botox “loosens” the scalp, reducing pressure on the perforating vasculature, thereby increasing blood flow and oxygen concentration. The enzymatic conversion of testosterone to dihydrotestosterone is oxygen dependent. In low-oxygen environments, the conversion of testosterone to dihydrotestosterone is favored; whereas in high-oxygen environments, more testosterone is converted to estradiol.4 Blood flow may therefore be a primary determinant in follicular health. Strategically placed Botox injections appear able to indirectly modify this variable, resulting in reduced hair loss and new hair growth in some men with androgenetic alopecia.
It's not a coincidence, it definitely is a link in the chain. MOST studies MUST agree AGA is caused by AR from the outset and this is the focus, they do not focus on other pathways. So its not really a coincidence if you are targeting a specific pathway.

The comment about botox increasing VEGF/HIF-1 was my own suggestion of the mechanism of botox inducing growth, rather than due to botox's muscle paralyzing effect as you initially implied here; Perhaps I misunderstood.

When I speak about cause I do not mean a single link in a chain, I am speaking about ROOT cause. In this case AR is not the root cause, mechanical stress would be if such a hypothesis were correct. If this could be definitively proven (I'm not saying it is) then would you treat AR as the cause or the tension problem?? It's interesting that the Botox study gets ignored even though the author has been open about it as well.
http://journals.lww.com/plasreconsur...ulinum.79.aspx

No one has discovered the root cause, thats why we have these hypothesis. PGD2 and immunity are probably downstream of androgen activity in the chain. It maybe multi-factor epigenetic. The monozygotic twin studies show that it IS a factor.

I was trying to suggest that the genes are the root cause predisposing individuals to AGA, and I believe there isnt a cause originating postnatally as a result of the environment. My rationale is that regardless of the cause, if you prevent the mediator that has detrimental effects on hair, the cause becomes irrelevant. If tension -> AR, then by targeting AR you can kill many birds with one stone. If the root cause (besides gene) is a trigger that sets off the chain, we cant undo it. But we can target active pathways that actively inhibit hair so long as they exert their effects. My methodology is firmly rooted to suppressing AR co-activators and upregulating WNT/Beta Catenin pathways, whereas you believe fibrosis/calcification needs to be addressed.

[UNBEAT]

any news from fgf11..

[pixels]

any news from fgf11..

News?

What about photographic evidence showing cosmetic improvements?

Oh wait... This guys writes 3 pages of "nigram" blah but not willing to show one image.