I think I've hacked it

[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

[Swooping]

Thank guys very interesting things mentioned here.

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

[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.

[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]

Swoop,

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

[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.

[UNBEAT]

Any news from fgf11?

[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]

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

[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?

[ShookOnes]

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

[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.

[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.

[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.

[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.