Ectodysplasin-a2 Induces Dickkopf 1 Expression In Human Balding Dermal Papilla Cells Overexpressing

Dimitri001

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You can actually kill safe, donor area hair (the one on the sides and back of your head which is supposedly resistant to androgens) by giving it sufficiently high amounts of T & DHT (essentially mimicking what is happening in balding follicles):

Effect of 5α-Dihydrotestosterone and Testosterone on Apoptosis in Human Dermal Papilla Cells
Thus, we investigated the influence of T and 5α-DHT on proliferation, cell death and bcl-2/bax expression in cultured dermal papilla cells (DPC) from nonbalding scalp regions of healthy volunteers. ... T and 5α-DHT induced apoptosis in DPC in a dose-dependent and time-related manner; in addition a necrotic effect due to T at 10–5M was found. ... These data suggest that DPC from nonbalding scalp regions do have the capacity to undergo apoptosis, but need a high androgen stimulus.


In other words, there is nothing particularly fancy or sensitive about the hairs on the top of your head, other than that they synthesize and are exposed to way too high amounts of androgens on a constant basis - the genetic aspect probably explains why some of these key enzymes and proteins regulating androgen synthesis are so imbalanced in these follicles.

But the underlined sentence is kind of ambiguous, it could be saying something other than how you're reading it. It could be saying that safe region hairs can bald, but they need a higher androgen stimulus than balding region hairs. So there sill could be a sensitivity difference.

Do you or anyone else know which reading is correct? Because if they safe region hairs are just as sensitive to androgens as balding region hairs, that would suggest that hairs are EXCLUSIVELY affected by DHT that they themselves generate (otherwise transplanted hairs would meet the same faith as other hairs in that region), which would be very interesting.

Finally, I will leave you with this paragraph from 1987, just so you get an idea of how long this has been known, and how little has been done about it:

View attachment 145731[3]


[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC52442/
[2] https://pubmed.ncbi.nlm.nih.gov/14556282/
[3] https://pubmed.ncbi.nlm.nih.gov/3598212/

Hmm... they say tht EpiT both inhibits 5AR and competes for the AR, but doesn't have any sides. I don't see how that could be so, given the sides ppl see with finasteride.

Maybe it hadn't been tested on enough people at the time to see sides.
 

whatevr

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I think that we are simply arguing causality and correlation here.

The question isn't so much of "is there a sensitivity?" but rather whether it is the cause or the consequence.

a) Was the hair follicle genetically sensitive from the start and subject to damage from even normal amounts of androgens?
b) Does the hair follicle synthesize excessive amount of androgens which then upregulate AR and make it even more sensitive to those very same androgens?

Chicken and egg question.

So far - there doesn't seem to be much evidence for A. There are two studies making a case for B, one of which I already linked:
https://www.researchgate.net/public...uctase_as_Indicators_of_Male-Pattern_Baldness
https://pubmed.ncbi.nlm.nih.gov/14757277/

In fact, the second study provides an interesting data point:

"The level of dihydrotestosterone (DHT) and the ratio of testosterone to epitestosterone (T/E ratio) in vertex hair from premature baldness subjects were higher than in the sample of non-baldness subjects (P<0.001, 0.001), whereas the levels of androgens in occipital hair from the same baldness group were not different."

This shows there is an obvious hormonal excess in the balding hairs, until proven otherwise, this cannot be excluded as the primary reason why they are dying. There is insufficient evidence to suggest that these balding hairs have some intrinsic sensitivity and that the 'non-balding' hairs wouldn't suffer the same fate - if exposed to equally high levels of androgens.

Additionally, it would be difficult to compare a balding and non-balding hair's response to similar levels of androgens because, at the point where the hair is visibly miniaturized enough to be identified as 'balding', it would already be exposed to super high androgen levels for several years, incur lots of cumulative damage and express tons of negative growth factors rendering it very susceptible to any further exposure, whereas that same level of androgens might take a few years to manifest damage on a 'non-balding' follicle.

Regarding the side-effect profile - it's difficult to say. There are plenty of studies suggesting all manner of things are safe which then proves false in the real world. We don't know, because unfortunately it has never been tried. It certainly makes sense as a topical attempt though. Regardless, this still doesn't treat the root issue. First the pathway of epitestosterone synthesis would need to be fully identified and described. Then, the balding DP would need to be assayed for levels and expression of proteins and genes involved in androgen synthesis and metabolism particularly those in the pathway of Epi-T synthesis. Some anomalies would certainly be found there. Targeting these proteins and attempting to restore a favorable balance of androgen synthesis would probably be a safer approach than applying the end-product to the scalp.
 

Armando Jose

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I think that we are simply arguing causality and correlation here.

The question isn't so much of "is there a sensitivity?" but rather whether it is the cause or the consequence.

a) Was the hair follicle genetically sensitive from the start and subject to damage from even normal amounts of androgens?
b) Does the hair follicle synthesize excessive amount of androgens which then upregulate AR and make it even more sensitive to those very same androgens?

Chicken and egg question.

So far - there doesn't seem to be much evidence for A. There are two studies making a case for B, one of which I already linked:
https://www.researchgate.net/public...uctase_as_Indicators_of_Male-Pattern_Baldness
https://pubmed.ncbi.nlm.nih.gov/14757277/

In fact, the second study provides an interesting data point:

"The level of dihydrotestosterone (DHT) and the ratio of testosterone to epitestosterone (T/E ratio) in vertex hair from premature baldness subjects were higher than in the sample of non-baldness subjects (P<0.001, 0.001), whereas the levels of androgens in occipital hair from the same baldness group were not different."

This shows there is an obvious hormonal excess in the balding hairs, until proven otherwise, this cannot be excluded as the primary reason why they are dying. There is insufficient evidence to suggest that these balding hairs have some intrinsic sensitivity and that the 'non-balding' hairs wouldn't suffer the same fate - if exposed to equally high levels of androgens.

Additionally, it would be difficult to compare a balding and non-balding hair's response to similar levels of androgens because, at the point where the hair is visibly miniaturized enough to be identified as 'balding', it would already be exposed to super high androgen levels for several years, incur lots of cumulative damage and express tons of negative growth factors rendering it very susceptible to any further exposure, whereas that same level of androgens might take a few years to manifest damage on a 'non-balding' follicle.

Regarding the side-effect profile - it's difficult to say. There are plenty of studies suggesting all manner of things are safe which then proves false in the real world. We don't know, because unfortunately it has never been tried. It certainly makes sense as a topical attempt though. Regardless, this still doesn't treat the root issue. First the pathway of epitestosterone synthesis would need to be fully identified and described. Then, the balding DP would need to be assayed for levels and expression of proteins and genes involved in androgen synthesis and metabolism particularly those in the pathway of Epi-T synthesis. Some anomalies would certainly be found there. Targeting these proteins and attempting to restore a favorable balance of androgen synthesis would probably be a safer approach than applying the end-product to the scalp.

All could be solved if the study would tested childrens (girls and boys) years before pùberty, at five years old by example,
https://pubmed.ncbi.nlm.nih.gov/14757277/
Comparative studies on level of androgens in hair and plasma with premature male-pattern baldness


Acording to my idea, there is not difference among healthy scalp hairs before or after puberty, also in both sexes.
 
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Dimitri001

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I think that we are simply arguing causality and correlation here.

The question isn't so much of "is there a sensitivity?" but rather whether it is the cause or the consequence.

a) Was the hair follicle genetically sensitive from the start and subject to damage from even normal amounts of androgens?
b) Does the hair follicle synthesize excessive amount of androgens which then upregulate AR and make it even more sensitive to those very same androgens?

Chicken and egg question.

So far - there doesn't seem to be much evidence for A. There are two studies making a case for B, one of which I already linked:
https://www.researchgate.net/public...uctase_as_Indicators_of_Male-Pattern_Baldness
https://pubmed.ncbi.nlm.nih.gov/14757277/

In fact, the second study provides an interesting data point:

"The level of dihydrotestosterone (DHT) and the ratio of testosterone to epitestosterone (T/E ratio) in vertex hair from premature baldness subjects were higher than in the sample of non-baldness subjects (P<0.001, 0.001), whereas the levels of androgens in occipital hair from the same baldness group were not different."

This shows there is an obvious hormonal excess in the balding hairs, until proven otherwise, this cannot be excluded as the primary reason why they are dying. There is insufficient evidence to suggest that these balding hairs have some intrinsic sensitivity and that the 'non-balding' hairs wouldn't suffer the same fate - if exposed to equally high levels of androgens.

Additionally, it would be difficult to compare a balding and non-balding hair's response to similar levels of androgens because, at the point where the hair is visibly miniaturized enough to be identified as 'balding', it would already be exposed to super high androgen levels for several years, incur lots of cumulative damage and express tons of negative growth factors rendering it very susceptible to any further exposure, whereas that same level of androgens might take a few years to manifest damage on a 'non-balding' follicle.

Regarding the side-effect profile - it's difficult to say. There are plenty of studies suggesting all manner of things are safe which then proves false in the real world. We don't know, because unfortunately it has never been tried. It certainly makes sense as a topical attempt though. Regardless, this still doesn't treat the root issue. First the pathway of epitestosterone synthesis would need to be fully identified and described. Then, the balding DP would need to be assayed for levels and expression of proteins and genes involved in androgen synthesis and metabolism particularly those in the pathway of Epi-T synthesis. Some anomalies would certainly be found there. Targeting these proteins and attempting to restore a favorable balance of androgen synthesis would probably be a safer approach than applying the end-product to the scalp.

Well, the quote you give seems to settle the question. It's not a difference in sensitivity, but in exposure.

Which is fascinating, because it seems to suggest that a HF is impacted exclusively by the androgens it itself "produces," otherwise you'd expect transplanted hairs to get miniaturized once transplanted, too.

And it makes me wonder about the questions you asked in your earlier post:

So if the ratio is normal in serum (there is no direct study, but this ratio is used for doping control tests, and if balding people had 5 times as much T / Epi-T they would be constantly failing and testing positive for doping) but is five times higher in balding follicles, why is that? Couple of possibilities:

1. The follicle is for some reason taking up way too much testosterone from serum (but not epitestosterone)?
2. Epitestosterone is not taken up from serum but synthesized in the follicle (in far too small amounts)?
3. Something else that I can't think of right now

Do you know, by the way, whether the ratio is different in bald men because of too much test or too little epitest?

Seems to me it could be both an overproduction of T and an underproduction of EpiT at the follicle itself and the reason castration would stop balding is because the HF overproduction of T in itself would not be sufficient to drive baldness, but when you combine it with T from the testes you break the threshold, therefore removing testes T through castration would stop balding.

This is interesting, from the same study you quoted:

In addition, we discovered the levels of DHT, testosterone, and DHT/T ratio in plasma from premature male pattern baldness were higher than in those of control subjects (P<0.001, 0.001, 0.005).

I've never heard that bald men have higher levels of DHT and T, perhaps this is just due to their small sample size. (baldness: 22, non-baldness: 13)
 
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theotherusero

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Given that this has been known about for 20 years now, it seems that an epitestosterone topical would be the logical treatment course for Androgenetic Alopecia then, wouldn't it, since it would tackle the root of the problem? Only one issue with that though - as a natural molecule it cannot be patented, and that's just not where the money is.

"The difference between the fathers of the two groups was more clear - the T/E ratio of the balding fathers (mean 46.41, range 32.99±68.34, p < 0.001) was about five times that of the nonbalding fathers (9.17, 6.34±11.41)."

Very interesting.

@whatevr @pegasus2 Epitestosterone topical or injected with mesotherapy could be a topical anti androgen with no sides?
It would be possible to create such compound?
 

pegasus2

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Very interesting.

@whatevr @pegasus2 Epitestosterone topical or injected with mesotherapy could be a topical anti androgen with no sides?
It would be possible to create such compound?
I don't think epitestosterone is obtainable at a reasonable price. It's also not likely to do much. It's more of a natural finasteride than anything else.
 
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