Updated Research and Knowledge - Cutting Edge

[bej]

I add a heaped teaspoon of Oleuropein powder into an 84ml bottle of Garnier fructis stemox, it dissolves quickly and perfectly

Thanks. I might have bailed out too early. I also heard from someone else that it dissolves in water. I made the assumption that alcohol would be best, but looks like that was a wrong assumption.

[bej]

deleted double post

[bej]

Green residue?

Does applying the dissolved olive leaf extract leave a green residue on the skin? Or too faint to notice?

[FeelsBad]

Slightly green but it's not noticeable

[Chemical]

Hey guys, sorry about disappearing all of a sudden. I took a holiday but I'm back now and I'll be continuing where I left off. Theres alot to talk about, and I'll get around to it once I've caught up with this thread. Anyways just thought I'd let you know I'm back to do some real research and answer some of your questions.

[monoid]

Hey guys, sorry about disappearing all of a sudden. I took a holiday but I'm back now and I'll be continuing where I left off. Theres alot to talk about, and I'll get around to it once I've caught up with this thread. Anyways just thought I'd let you know I'm back to do some real research and answer some of your questions.

Glad you are back!

Thanks for your new post! I've learned a lot. However, I strongly advise against trying this stuff:

Polygonum Multiflorum (Fo-Ti)

This plant is called 何首乌 (He-shou-wu) in Traditional Chinese medicine and is known to be highly hepatotoxic (toxic to liver). The root of this plant is very black, hence ancient Chinese people related it to black, healthy hair (common alternative medicine reasoning, which is of course BS). There has been numerous cases of liver damage caused by this substance.

[InBeforeTheCure]

Nice to see you're still among the living, Chemical.

A while back you posted this study:

Androgen treatment revealed a significant decrease in the cytoplasmic/total β-catenin protein ratio and upregulation of the activity of glycogen synthase kinase-3β in DPC, indicative of canonical Wnt pathway inhibition.

http://www.ncbi.nlm.nih.gov/pubmed/22283397

When they say there is a "significant decrease in the cytoplasmic/total beta-catenin protein ratio", where is the beta-catenin now? In the nucleus bound to AR, dragged there by DHT-induced AR translocation to the nucleus?

In A Mouse Model of Androgenetic Alopecia, the authors find that AR binds beta-catenin in a DHT-dependent manner.

Co-immunoprecipitation of AR and beta-catenin:



Another study: Keratinocyte Growth Inhibition through the Modification of Wnt Signaling by Androgen in Balding Dermal Papilla Cells

To examine whether the differences in HaCaT cell proliferation in coculture with AGA and non-AGA male DP cells were mediated by the action of AR and β-catenin, we investigated the subcellular distribution of AR and β-catenin in the cultured DP cells after treatment with DHT and/or Wnt3a. In DP cells of AGA40M (Fig. 2B2B),), AR was diffusely distributed in cytoplasm, and β-catenin was present in pericellular cytoplasm in the absence of DHT and Wnt3a. In the presence of DHT, AR was significantly translocated to the nucleus, whereas cytoplasmic distribution of β-catenin was not so changed. When the DP cells were treated with Wnt3a, AR was present in the cytoplasm. In contrast, β-catenin was strongly enhanced and exhibited filamentous appearance. With the addition both of DHT and Wnt3a, AR and β-catenin were distributed in the nucleus in which they were colocalized. Similar distribution patterns of AR and β-catenin were observed in DP cells from other AGA males (Fig. 2C2C).

Next we show that there is intracellular localization of AR and β-catenin in a ligand-free condition in DP cells of non-AGA males (Fig. 2D2D).). Addition of either DHT or Wnt3a yielded this same intracellular localization in AGA40M or other male AGA cells. When DHT and Wnt3a were added together, colocalization of AR and β-catenin in the nucleus was sparse.

In AGA40M, after Wnt is added, beta-catenin remains locked down in the cytoplasm even in the absence of DHT:


Localization of AR and β-catenin in DP cells. A, DP cells of AGA40M and non-AGA male were treated with DHT (10−9 m) for various times (10 min, 1 h, 2 h). The cells were fixed and labeled with anti-AR and anti-β-catenin antibodies, followed by fluorescent second antibodies. All images were captured using confocal laser-scanning microscopy. DP cells of AGA40M (B) and from other AGA males (C) and non-AGA male (D) were cultured in the absence of both DHT and Wnt3a (−), presence of DHT, presence of Wnt3a (20 ng/μl) (W), or presence of both DHT and Wnt3a (WD) for 2 h. The cells were visualized as in A. Fluorescent images shown in green are AR, whereas the images in red are β-catenin. Merged images are shown in the right panels. Bar, 10 μm.

By using image analysis software, we examined the degree of nuclear colocalization of AR and β-catenin semiquantitatively using the ratio of merged dots in the nucleus/AR dots in cells treated with both Wnt3a and DHT (Fig. 3A3A).). The ratios in DP cells from AGA males was higher by 2.5-fold than in DP cells of non-AGA males. These results indicate that AR and β-catenin in the nucleus was more highly colocalized in DP cells of AGA40M and other AGA males than in that of non-AGA males.

Co-localization of AR and beta-catenin:


C, AGA40M cells and non-AGA DP cells were treated with either DHT and/or Wnt3a for 2 h. Immunoprecipitation (IP) with anti-AR antibody was carried out using each cell lysate. Precipitates were analyzed by immunoblotting with each antibody. The upper panel shows the detection of β-catenin after immunoprecipitation with anti-AR antibody and the lower panel shows the detection of AR on the same membrane. D, Presence of DHT; W, presence of Wnt3a; WD, presence of both DHT and Wnt3a; WB, western blot.

This shows that in AGA40M, AR/beta-catenin binding is androgen-independent. This is different from the "mouse model" study where AR/beta-catenin binding was androgen-dependent. I guess this goes back to the FGF11 hypothesis that AGA becomes androgen-independent given enough time and androgen exposure, but virtually no work has been done to investigate this in any depth, so for now we don't really know.

If there is ligand-independent binding of AR/beta-catenin, AR antagonists that compete with androgens by binding to the AR LBD would have limited effectiveness because they can only counteract androgen-dependent AR activation. Something like MDV3100 would be more effective because it actually degrades the AR. There is a guy claiming to use MDV3100 who had dramatic results that he was unable to get with RU alone: https://www.baldtruthtalk.com/thread...-and-MDV3100-2

EGCG may be helpful for that as well -- it potently inhibits AR transcription in vitro. However, it has a short half-life, so you would have to apply it several times a day, and even then I'm not sure how potent 2-3% EGCG (it's not soluble beyond that amount) is in vivo.

Anyway...Of course, as you know, dermal beta-catenin is critical for inducing epithelial hair follicle gowth.

β-catenin activity in the dermal papilla regulates morphogenesis and regeneration of hair

The activity of keratinocytes in the hair follicle is regulated by signals from a specialized mesenchymal niche, the dermal papilla. Here, mice expressing cre recombinase in the dermal papilla were developed to probe the interaction between follicular keratinocyte populations and the dermal papilla in vivo. Inactivation of the β-catenin gene within the dermal papilla of fully developed hair follicles results in dramatically reduced proliferation of the progenitors and their immediate progeny that generate the hair shaft and, subsequently, premature induction of the destructive phase of the hair cycle (catagen). It also prevents regeneration of the cycling follicle from stem cells resident in the permanent portion of the follicle. Gene expression analysis reveals that β-catenin activity in the dermal papilla regulates at least two signaling pathways, FGF and IGF, that can mediate the inductive effects of the DP on keratinocytes. This study reveals a reciprocal signaling loop that employs Wnt/β-catenin signaling in both epithelial progenitor cells and their mesenchymal niche to govern and coordinate the interactions that are essential for the function of these two compartments.

Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline

Although the hair shaft is derived from the progeny of keratinocyte stem cells in the follicular epithelium, the growth and differentiation of follicular keratinocytes is guided by a specialized mesenchymal population, the dermal papilla (DP), that is embedded in the hair bulb. Here we show that the number of DP cells in the follicle correlates with the size and shape of the hair produced in the mouse pelage. The same stem cell pool gives rise to hairs of different sizes or types in successive hair cycles, and this shift is accompanied by a corresponding change in DP cell number. Using a mouse model that allows selective ablation of DP cells in vivo, we show that DP cell number dictates the size and shape of the hair. Furthermore, we confirm the hypothesis that the DP plays a crucial role in activating stem cells to initiate the formation of a new hair shaft. When DP cell number falls below a critical threshold, hair follicles with a normal keratinocyte compartment fail to generate new hairs. However, neighbouring follicles with a few more DP cells can re-enter the growth phase, and those that do exploit an intrinsic mechanism to restore both DP cell number and normal hair growth. These results demonstrate that the mesenchymal niche directs stem and progenitor cell behaviour to initiate regeneration and specify hair morphology. Degeneration of the DP population in mice leads to the types of hair thinning and loss observed during human aging, and the results reported here suggest novel approaches to reversing hair loss.

A combination of cellular senescence and apoptosis in DP cells as well as maybe "effective" loss of DP cells due to AR binding of beta-catenin -> progressively lower actual/effective DP cell count -> hair follicle miniaturization

Krajcik et al showed that vellus hairs from bald scalp progressively recover and grow thick terminal hair again after transplanted onto SCID mice. Why?

There was another study done a few years before Krajcik where they transplanted (healthy) human hair onto SCID mice. They found that the follicles soon went into something called dystrophic catagen -- large-scale apoptosis of the hair follicle -- followed by regeneration. Perhaps this process "resets" the follicle by removing senescent cells and other cells with screwy gene expression.

Interestingly enough, topical estrogen accelerates hair regrowth in mice after chemotherapy-induced alopecia by favoring the dystrophic catagen response pathway to damage. Maybe this is one reason (among others) why estrogen is so effective at regrowing hair in even advanced cases of AGA.

[Seuxin]

Hello Chemical,

What about your progress ( Oleuropein, etc....)

Thanks

[InBeforeTheCure]

Another study: Keratinocyte Growth Inhibition through the Modification of Wnt Signaling by Androgen in Balding Dermal Papilla Cells



In AGA40M, after Wnt is added, beta-catenin remains locked down in the cytoplasm even in the absence of DHT:


Localization of AR and β-catenin in DP cells. A, DP cells of AGA40M and non-AGA male were treated with DHT (10−9 m) for various times (10 min, 1 h, 2 h). The cells were fixed and labeled with anti-AR and anti-β-catenin antibodies, followed by fluorescent second antibodies. All images were captured using confocal laser-scanning microscopy. DP cells of AGA40M (B) and from other AGA males (C) and non-AGA male (D) were cultured in the absence of both DHT and Wnt3a (−), presence of DHT, presence of Wnt3a (20 ng/μl) (W), or presence of both DHT and Wnt3a (WD) for 2 h. The cells were visualized as in A. Fluorescent images shown in green are AR, whereas the images in red are β-catenin. Merged images are shown in the right panels. Bar, 10 μm.



Co-localization of AR and beta-catenin:


C, AGA40M cells and non-AGA DP cells were treated with either DHT and/or Wnt3a for 2 h. Immunoprecipitation (IP) with anti-AR antibody was carried out using each cell lysate. Precipitates were analyzed by immunoblotting with each antibody. The upper panel shows the detection of β-catenin after immunoprecipitation with anti-AR antibody and the lower panel shows the detection of AR on the same membrane. D, Presence of DHT; W, presence of Wnt3a; WD, presence of both DHT and Wnt3a; WB, western blot.

The weird thing is looking at Figure 4, it seems like Tcf/Lef are still activating their target genes (higher luciferase activity w/ Tcf/Lef responsive promoter). Also in non-AGA males, DHT looks to be about as good as Wnt signaling for activating Tcf/Lef target genes???

[Chemical]

Glad you are back!

This plant is called 何首乌 (He-shou-wu) in Traditional Chinese medicine and is known to be highly hepatotoxic (toxic to liver). The root of this plant is very black, hence ancient Chinese people related it to black, healthy hair (common alternative medicine reasoning, which is of course BS). There has been numerous cases of liver damage caused by this substance.

I was under the impression topical application wouldnt cause much systemic absorption. I havent taken it but the studies demonstrated that it had alot of potential to stimulate the proliferation of DPC/Keratinocytes, not the traditional beliefs of the Chinese. We dont pass hearsay as scientific proof around here. Thank you for the welcome!

@InBeforeTheCure

A study as a welcome present, what more could I ask for. Excellent analysis as always.

Keratinocyte Growth Inhibition through the Modification of Wnt Signaling by Androgen in Balding Dermal Papilla Cells

When HaCaT cells were cocultured with an AGA patient-derived DP cell line, AGA40M, the number of HaCaT cells was not influenced by the addition of DHT. But the number of HaCaT cells was significantly increased in the presence of Wnt-3a, and this growth was significantly suppressed by the addition of DHT (Fig. 1B1B).). A similar effect of DHT was detected in the coculture of the HaCaT cells with DP cells from other AGA patients (data not shown). In the coculture with DP cells of non-AGA males, the number of HaCaT cells was also increased by the addition of Wnt3a, but significant growth suppression due to DHT was not detected (Fig. 1C1C).

Wnt3a treatment significantly accelerated the growth of HaCaT cells in the single cell culture, but the addition of DHT did not affect growth (Fig 1D1D).). On the other hand, the growth of DP cells was not affected by Wnt3a in single cell culture conditions (data not shown). It has been reported that androgen does not influence growth of DP cells in a single cell culture condition (26,27). These results indicate that Wnt3a-dependent keratinocyte proliferation is reduced by DHT in the coculture with AGA DP cells. This suggests that this DHT effect is not a direct action on keratinocytes but is mediated through DP cells.

There is a very strong genetic component here with the AGA DPC. The cells respond to the DHT by further antagonizing the growth of the adjacent cells in addition to the DHT mediated TCF/LEF suppression:

DP cells were transfected with a reporter plasmid in which the luciferase gene was connected downstream to the Lef/Tcf-binding promoter. Lef/Tcf-mediated transcriptional activity was induced by treatment with Wnt3a in AGA40M cells, but this induction was significantly suppressed by the addition of DHT (Fig. 4A4A).). The same result was observed in DP cells of other AGA male. In contrast, in DP cells of non-AGA males, the transcriptional activity was not suppressed by DHT. These results indicate that the Wnt-β-catenin signaling pathway is negatively influenced by ligand-activated AR in DP cells of AGA but not DP cells of non-AGA males.

Regarding this:

The weird thing is looking at Figure 4, it seems like Tcf/Lef are still activating their target genes (higher luciferase activity w/ Tcf/Lef responsive promoter). Also in non-AGA males, DHT looks to be about as good as Wnt signaling for activating Tcf/Lef target genes???

This should answer your question:

It has been reported that Tcf-4 is a downstream target of AR in skeletal muscle (28); therefore, we investigated expression of Tcf-4 protein in the DP cells by immunoblotting. Both AGA and non-AGA DP cells expressed Tcf-4 protein (Fig. 4C4C).

AR can and does use Beta Catenin to exert some of its anabolic effects so it makes sense that it interacts with TCF.

When they say there is a "significant decrease in the cytoplasmic/total beta-catenin protein ratio", where is the beta-catenin now? In the nucleus bound to AR, dragged there by DHT-induced AR translocation to the nucleus?

Exactly like you've said:

Thus, we assumed that AGA-derived DP cells specifically inhibited the growth of keratinocyte and the potential of Lef/Tcf mediated transcription might be due to differences in translocation of AR and β-catenin to the nucleus. As expected, in the presence of DHT and Wnt3a, a significantly higher ratio of AR to β-catenin was cotranslocated to the nucleus in DP cells of AGA than in DP cells of non-AGA males. Considering this result together with analysis of Lef/Tcf mediated transcription, it is conceivable that nuclear interaction of liganded AR with β-catenin inhibits transcriptional activity in DP cells of AGA. In fact, direct binding of AR and β-catenin was more frequent in AGA DP cells than non-AGA DP cells as determined by the present immunoprecipitation analysis.

In AGA40M, after Wnt is added, beta-catenin remains locked down in the cytoplasm even in the absence of DHT:

This shows that in AGA40M, AR/beta-catenin binding is androgen-independent. This is different from the "mouse model" study where AR/beta-catenin binding was androgen-dependent. I guess this goes back to the FGF11 hypothesis that AGA becomes androgen-independent given enough time and androgen exposure, but virtually no work has been done to investigate this in any depth, so for now we don't really know.

This is something I had a hard time accepting. Its not so obvious in the pictures but I can see what you're talking about, however I am still reluctant to jump to this conclusion. If AR does indeed permanently change the response of DPC to T/DHT then it means the sensitivity of AGA to androgens increases as time goes on making regrowth even harder for individuals.

If there is ligand-independent binding of AR/beta-catenin, AR antagonists that compete with androgens by binding to the AR LBD would have limited effectiveness because they can only counteract androgen-dependent AR activation. Something like MDV3100 would be more effective because it actually degrades the AR. There is a guy claiming to use MDV3100 who had dramatic results that he was unable to get with RU alone: https://www.baldtruthtalk.com/thread...-and-MDV3100-2

Absolutely. If AR is upregulated then preventing the binding of AR to LBD or translocating to the nucleus will do jack sh!t if the AR is taking up beta-catenin. We would need something that can interact with the stability of AR. Even EGCG would have little effect seeings as its already a very mild AR antagonist (post coming soon).

Anyway...Of course, as you know, dermal beta-catenin is critical for inducing epithelial hair follicle gowth.

A combination of cellular senescence and apoptosis in DP cells as well as maybe "effective" loss of DP cells due to AR binding of beta-catenin -> progressively lower actual/effective DP cell count -> hair follicle miniaturization

Krajcik et al showed that vellus hairs from bald scalp progressively recover and grow thick terminal hair again after transplanted onto SCID mice. Why?

There was another study done a few years before Krajcik where they transplanted (healthy) human hair onto SCID mice. They found that the follicles soon went into something called dystrophic catagen -- large-scale apoptosis of the hair follicle -- followed by regeneration. Perhaps this process "resets" the follicle by removing senescent cells and other cells with screwy gene expression.

Like you say, the AGA DPC are preprogrammed to respond to DHT in a self-destructive manner so long as they contain the genetic code specific to the frontal scalp. If you remove Androgens from the equation they will function as normal but theres absolutely no way we can completely abolish T/DHT. I've said before about the DPC having direct access to the blood supply's androgens, so it looks like a hopeless battle trying to use the existing DPC to maintain hair. And since prenatal DPC dont exactly disappear and only become senescent, the code is still present, so even if you manage to achieve regrowth and the cells go into anagen, the DPC will still be susceptible. The only solution I see is hijacking the keratinocytes ability to form HF when over-expressed with beta-catenin. That way the DPC that are formed might not have the sensitivity to DHT. The guys at histogen (or was it replicel) claimed to have seen progressive regrowth and maintenance with infrequent injections of powerful mitogenic growth factors like HGF.

My current progress

I stopped everything around 2 months ago. Before I stopped I was using the following for two weeks:

Minox by itself - morning
Minox + EGCG - night
Minox + OL - night
Water + VPA - night
Keto + Mico - morning & night
Evening primrose - night

After stopping, a week later I saw a ridiculous amount of vellus hairs all along my nw0 hairline, so much that it looked like I'd cured my recession. I strongly suspect this a residual effect of all the treatments finally showing results - or it could be because I stopped. I really really regret not taking pictures which means we're going to have to write it off as not happening but I have hope that I'll be able to recreate the results again and this time will take pictures. I didnt have my treatments with me so I couldnt continue but I had good density and I was quite happy. 6 weeks later I started receding again and lost all the vellus hairs but surprisingly I didnt lose the hairs on the side I was concentrating all my treatments (pics soon). I've got more density than I've had in the past year and I'm back on minox, keto, mico, EPO and borage oil. The EGCG is quite irritating so I've dropped it and I've ordered some more OL. I've managed to regrow hair using only minox and OL in the past - without an AR blocker, so the EPO and Borage oil should definitely help. I might use the VPA again and I'm considering creating a topical out of my fin tablets.

[monoid]

I was under the impression topical application wouldnt cause much systemic absorption. I havent taken it but the studies demonstrated that it had alot of potential to stimulate the proliferation of DPC/Keratinocytes, not the traditional beliefs of the Chinese. We dont pass hearsay as scientific proof around here. Thank you for the welcome!

Well if it has solid scientific proof then OK. Be careful with it since its hepatotoxicity is confirmed.

[burtandernie]

I think some people on here like chemical should be researching an actual treatment for MPB. Some of the guys here know as much as the researchers almost. Can you use those supplements orally instead of having to mix a topical vehicle? how do you know using that stuff causes any hair growth verses it being from the minox which is obviously one of the best regrowth agents.
What is the best and safest way to stop the most androgens?

[InBeforeTheCure]

AR can and does use Beta Catenin to exert some of its anabolic effects so it makes sense that it interacts with TCF.

But in the stains, it looks like very little AR or beta-catenin is in the nucleus after Wnt is added in AGA40M?

Anyway, I'm wondering if AR binding to beta-catenin could maybe alter the way in which beta-catenin interacts with Wnt response elements -- for instance by recruiting HATs and HDACs to remodel chromatin structure, or by other interactions with certain transcription factors -- and thereby downregulate some Wnt target genes and upregulate others. DKK1 for example is actually a Wnt target gene -- and indeed DKK1 is upregulated over 2x in response to Wnt in DPCs -- and as you've pointed out DKK1 is (further) upregulated in balding DP cells in response to DHT. The new gene transcription "profile" of DPCs in response to Wnt could then fail to induce epithelial stem cell activation. Highly speculative, but could it be possible?

This is something I had a hard time accepting. Its not so obvious in the pictures but I can see what you're talking about, however I am still reluctant to jump to this conclusion. If AR does indeed permanently change the response of DPC to T/DHT then it means the sensitivity of AGA to androgens increases as time goes on making regrowth even harder for individuals.

Increased sensitivity to androgens could happen by

- Upregulation of AR
- An increase in androgen-independent activation of AR. Let's say z is the threshold in AR activation that causes hair loss, x is the androgen-independent level of activation, and y is activation caused by androgens. And let's say androgen-independent activation is very low in early stages of balding, but rises somehow over time as a result of DHT-bound AR transcribing its target genes. Left untreated, x rises over time and it takes less y to push x + y over the threshold (z). Eventually x > z and no anti-androgen or even castration could push AR activation below z -- the DPC's inductive ability is lost.

In this model castration > dut > fin. A prediction of this model is that someone who is maintaining on fin who goes on dut, regrows some on dut, but then switches back to fin would lose the hair he gained on dut (is this how it is in reality?). This would be expected based on a model where AR is upregulated or androgen-independent activation of AR increases over time with exposure to DHT, or both. At least, I think it would fit such a model better than a model where DP cells in recently lost hair are "repaired" in response to androgen removal.

I'm just speculating here, of course.

Absolutely. If AR is upregulated then preventing the binding of AR to LBD or translocating to the nucleus will do jack sh!t if the AR is taking up beta-catenin. We would need something that can interact with the stability of AR. Even EGCG would have little effect seeings as its already a very mild AR antagonist (post coming soon).

Sulforaphane? Don't know how good it would be in practice though. Seems to have a half-life of only a couple hours too, so even if it did work you might have to use it 20 times a day or so, including at night.

Like you say, the AGA DPC are preprogrammed to respond to DHT in a self-destructive manner so long as they contain the genetic code specific to the frontal scalp. If you remove Androgens from the equation they will function as normal but theres absolutely no way we can completely abolish T/DHT. I've said before about the DPC having direct access to the blood supply's androgens, so it looks like a hopeless battle trying to use the existing DPC to maintain hair. And since prenatal DPC dont exactly disappear and only become senescent, the code is still present, so even if you manage to achieve regrowth and the cells go into anagen, the DPC will still be susceptible. The only solution I see is hijacking the keratinocytes ability to form HF when over-expressed with beta-catenin. That way the DPC that are formed might not have the sensitivity to DHT. The guys at histogen (or was it replicel) claimed to have seen progressive regrowth and maintenance with infrequent injections of powerful mitogenic growth factors like HGF.

Yes, but dystrophic catagen could remove senescent cells and other malfunctioning cells from the cell cycle. Then dermal stem cells regenerate the dermal papilla. Sure, over time it will malfunction again, but you would just need maintenance treatments then to stop that from happening. And then eventually, once the technology is available, you could get the AR gene knocked down permanently in your scalp and never have to worry about AGA again.

[UNBEAT]

so CHIMICAL , INBEFORETHECURE : fgf 11 with his theory about AR genes and what he is trying to do is right , or not??? It can be like a cure?

[InBeforeTheCure]

Anyway, I'm wondering if AR binding to beta-catenin could maybe alter the way in which beta-catenin interacts with Wnt response elements -- for instance by recruiting HATs and HDACs to remodel chromatin structure, or by other interactions with certain transcription factors -- and thereby downregulate some Wnt target genes and upregulate others. DKK1 for example is actually a Wnt target gene -- and indeed DKK1 is upregulated over 2x in response to Wnt in DPCs -- and as you've pointed out DKK1 is (further) upregulated in balding DP cells in response to DHT. The new gene transcription "profile" of DPCs in response to Wnt could then fail to induce epithelial stem cell activation. Highly speculative, but could it be possible?

The more I look into it, the more I think this is probably correct. It's probably not so much that AR binds beta-catenin and prevents it from acting (as FGF11 thought). I think it's more likely that AR hijacks the Wnt pathway for its own nefarious purposes by binding to beta-catenin and altering the way that beta-catenin/TCF4 interacts with Wnt response elements, either enhancing them or (relatively) repressing them. From this model you can actually derive, for example, why PGD2 is upregulated in AGA with reference to both theory and experimental results. You can also imagine how a similar mechanism could actually account for why androgens stimulate facial hair growth while causing hair loss on your head. However, I'd like to develop this idea further before really getting into that (maybe I'll create a new thread sometime).

This is not exactly a novel idea, as something similar is known to happen in prostate cells, for example.

so CHIMICAL , INBEFORETHECURE : fgf 11 with his theory about AR genes and what he is trying to do is right , or not??? It can be like a cure?

I think the answer is "I don't know".