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jpj
New member
Username: Jpj

Post Number: 340
Registered: 07-2006
Posted on Sunday, June 10, 2007 - 07:29 pm:   Edit Post Delete Post

As good as you will read...................


http://home.arcor.de/gekkehenk/HW/HW%20Topical/03.%20Role%20of%20TGF-beta2%20in% 20the%20human%20hair%20cycle..pdf
 

Tom Hagerty
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Username: Admin

Post Number: 3293
Registered: 01-2003
Posted on Monday, June 11, 2007 - 01:32 pm:   Edit Post Delete Post

jpj:

"As good as you will read..................."

That's an understatement. Very few people will read the full ten-page scientific article so I'm going to make extensive quotations from it that will summarize the conclusions of this Japanese team:
TGF-b2 was localized at the outermost layer of ORS cells, whereas TGF-b3 was seen at the hair cortex and the hair cuticle in the keratogenous zone.

Deposition of TGF-b2 was only observed in the early catagen hair follicles, characterized by
the upward removal of hair shaft from the DP, decrease of hair color due to the down-regulation
of melanogenesis, and the increased thickness of the connective tissue sheath.

This staining pattern was hardly found in any anagen hair follicles. In an organ culture system, similar TGF-b2 deposition in the bulb area was detected when hair follicles started catagen-like morphological changes.

Appearance of active forms of both initiator caspase-9 and effector caspase-3 suggested that TGF-b is capable of triggering the caspase network in the epithelial cells.

These lines of evidence provided new insights into the mechanism of TGF-b-induced cell death,
showing that TGF-b contributes to the synthesis of certain caspases and activation of the intrinsic caspase network, which are essential steps leading to catagen progression.

If TGF-b is responsible for the induction of catagen, suppression of TGF-b could prevent entry into catagen or progression of catagen.

Extensive screening of plant extracts showed that hydrangea extract was able to suppress TGF-b action. Using an organ culture system, the effect of hydrangea extract on hair growth was examined. The extract resulted in prolonged hair growth compared to the control, suggesting suppression of catagen entry. Caspase activation was also suppressed in the presence of the extract.

Recent investigations suggested that 5aR-II is present in axillary, pubic and beard hair, and in the case of scalp hair, it is present dominantly at the forehead. Indeed inhibition of 5aR-II activity in vivo was effective in preventing hair loss.

[This is the scientists' summary of their article.]

In male pattern baldness, the following sequence of reactions is expected to occur: testosterone delivered to hair follicles is converted to DHT by type II 5a-reductase; DHT then stimulates the synthesis of TGF-b2 in dermal papilla cells; TGF-b2 induces epithelial cells to promote up-regulation and activation of caspase-9 and caspase-3 in matrix cells, resulting in the removal of epithelial cells by apoptotic cell death. We named this series of reactions the ‘‘catagen cascade’’.

Our recent investigations further suggest that this cascade involves a feedback mechanism, in which TGF-b2 plays a central role. In addition, other signal mechanisms influence this cascade. Therefore, it is difficult to envisage a simple inhibition strategy to stop the cascade. In order to have an effective countermeasure against male pattern baldness, it is important to suppress these complicated reactions at multiple stages. For example, the combination of a type II 5a-reductase inhibitor, a TGF-b2 antagonist and a caspase inhibitor might be effective to prevent male pattern baldness.

jpj, I think it's a good idea while reading the article to have an understanding of the difference between mesenchymal and epithelial cells. TNFs (tumor necrosis factor): These are cytokines that can cause cell death - apoptosis. And here is a definition of caspases: These are enzymes that are responsible for the breakdown of the cell during apoptosis by cleaving (splitting) numerous cellular proteins.

Thanks for linking to this article - As Good As It Gets - one of my favorite movies by the way.

Look up Hydrangea on Wikipedia. You'll notice way down in the article: "Hydrangeas are one of very few plants that accumulate aluminium. Aluminium is released from acidic soils, and in some species, forms complexes in the hydrangea flower giving them their blue colour."
 

jpj
New member
Username: Jpj

Post Number: 341
Registered: 07-2006
Posted on Monday, June 11, 2007 - 01:57 pm:   Edit Post Delete Post

Tom,

We KNOW that barley proanthocyandins inhibit TGF-beta 1 and 2 expression. Barley is available as a liquid extract (by the gallon too, very cheap) but is much available in beer. The boiling beer (until it loses about half its volume) should make alot of barley availed to anyone who wishes to add it to their shampoo, etc.

I have read in the past that green tea inhibited TGF-beta 1 and 2, but haven't been able to find it in the past few days.

Finasateride lowers TGF_beta expression in the scalp by roughly 30 percent, and thats not enough.

I'll look up hydragena.............but it sounds exotic and expensive. Probably not alot of this cheaply available.
 

Jeff M
New member
Username: Vm17

Post Number: 9
Registered: 11-2006
Posted on Tuesday, June 12, 2007 - 06:46 am:   Edit Post Delete Post

Thanks for the link JPJ, it was interesting to read. My knowledge of the more complicated anatomical (not sure if thats a word)aspects regarding hairloss is pretty limited but I'm slowly getting there.

So from your previous post, potentially rubbing barley in liquid extracts or beer into your scalp could help prevent hairloss? Id be willing to try it if that was the case.
 

Gabe
New member
Username: Gabe

Post Number: 117
Registered: 07-2006
Posted on Tuesday, June 12, 2007 - 10:29 am:   Edit Post Delete Post

jpj

i actually found cheap hydrangea on swanssons

http://www.swansonvitamins.com/webapp/wcs/stores/servlet/ProductDisplay?storeId= 10001&langId=-1&catalogId=10051&SourceCode=INT999&productId=19262&R=8799&healthC oncernDropBox=null&Ntx=mode%2Bmatchallpartial&Ntt=hydrangea&keyword=hydrangea&N= 4294967183&brandDropBox=null&productDropBox=null&Ntk=Level1

Not sure if it's the right thing though.
 

jpj
New member
Username: Jpj

Post Number: 342
Registered: 07-2006
Posted on Tuesday, June 12, 2007 - 12:35 pm:   Edit Post Delete Post

jeff m

Id slow-(lower temp) boil the beer until it lost a third of its volume, then re-add some alcohol back to it for penetration first. Barley proanthocyandins have been shown to inhibit tgf beta 1 and 2, but the wouldn't be too awfully concentrated in regular beer.


There is barley extract that you can buy very cheap. I think they sell it by the gallon. It would probably have alot more proanthocyandin content. .


gabe,
Id rather inhibit tgf beta topically. Im scared of the side effects of 24 hour inhibition of this pathway. 12 might be ok, but just shutting it down altogether systemically...............I wonder. Its pro-collagen too, which makes your face look young.
 

Gabe
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Username: Gabe

Post Number: 118
Registered: 07-2006
Posted on Tuesday, June 12, 2007 - 06:02 pm:   Edit Post Delete Post

jpj

Is internal nettle root and green tea also included in this tgf beta problem?
 

Jeff M
New member
Username: Vm17

Post Number: 10
Registered: 11-2006
Posted on Wednesday, June 13, 2007 - 12:09 am:   Edit Post Delete Post

thanks for that jpj. I live in Australia, so ill have to check around and see if someone sells barley extract. if not, ill look around the net for someone selling the stuff.
 

Downunder
New member
Username: Downunder

Post Number: 30
Registered: 08-2006
Posted on Thursday, June 14, 2007 - 04:11 am:   Edit Post Delete Post

jpj/Tom

Can I ask what are you trying to achieve through the TGF-b inhibition?

The hair follicle goes through a natural cycle Anagen .. So it is only natural that something is going to trigger the process of a shed and beginning of an new cycle. In this case it is believed that TGF-b may be responsible for triggering the event.

So inhibit TGF-b and you are effectively trying to stop this natural process. So you have follicles that cannot enter into catagen and in theory remain frozen in the hair cycle.

So for the person noticing hair loss the hairs are getting weaker. This weakness may cause further loss as the hairs do not cope with normal daily activity. So you want to inhibit TGF-b and freeze it in the cycling process. Your situation is that you have lost some hair, so you freeze cycling. The remaining hair is weak and some is going to fall out through activity, the rest is just hanging there waiting to be brushed out etc. In theory no new hairs shall grow as you have interrupted the natural hair cycling process.

It appears that doing this may be at best trying to slow the process and I know jpj is quite interested in that aspect. But there would appear to be little hope of recovery as you have frozen the hair cycle and prevented the ability for the body to grow a newer stronger hair. Let me know if I am interpreting this incorrectly.

I see the catagen cascade as an important part of the cycle.

Tom, you did not comment as to whether you see this as something assisting the SE. Could you comment?
 

Tom Hagerty
Moderator
Username: Admin

Post Number: 3297
Registered: 01-2003
Posted on Thursday, June 14, 2007 - 10:44 am:   Edit Post Delete Post

Downunder:

"So inhibit TGF-b and you are effectively trying to stop this natural process. So you have follicles that cannot enter into catagen and in theory remain frozen in the hair cycle."

In one paragraph of the article jpj linked to is the phrase, "prevent entry into catagen or progression of catagen," but in other paragraphs there is the phrase, "suppression of catagen entry."

I don't think there is any evidence that natural inhibitors of TGF-b actually "prevent" entry into catagen; they just slow down the premature entry of the hair follicle into this retrogressive stage of the hair cycle. By natural I mean phytochemicals like the proanthocyandins in barley or herbals like the extract of hydrangea. I prefer getting the phytochemicals from real foods; jpj prefers their topical application although he also advocates eating some foods high in beneficial phytochemicals.

Male pattern baldness develops because of a shorter growing stage (anagen). The hair follicles enter into the catagen stage prematurely. As MPB progresses there is also a progressive shortening of the anagen stage. A short anagen stage usually means miniaturized hair follicles. Miniaturized follicles produce hair of increasingly smaller diameter - vellus hairs. Anything that can counteract the shortening of the growing stage of the hair cycle - that is, postpone the entry into catagen - should be of benefit to people suffering from thinning hair.

Perhaps chemicals, not natural phytochemicals but synthesized compounds, will be found that can actually "prevent" the hair follicle from entry into catagen. I think this would not be helpful to people with hair loss problems. As you said, "I see the catagen cascade as an important part of the cycle." That is my opinion too.

I don't see how the SE fits into all of this. Perhaps it doesn't.
 

Fred Smith
New member
Username: Hair_king

Post Number: 11
Registered: 07-2006
Posted on Friday, June 15, 2007 - 10:00 am:   Edit Post Delete Post

I read through this thread several times. It is hard reading but it is definitely an education about hair loss problems. I never realized hair loss and treatment options were so complicated. I am optimistic about the future though. someone is going to figure this all out.
 

jpj
New member
Username: Jpj

Post Number: 344
Registered: 07-2006
Posted on Friday, June 15, 2007 - 03:07 pm:   Edit Post Delete Post

Fred,

Yes, its complicated. I think the nearest term-solution-is what Dr. Loren Pickart has said on his own forum, the cloning of "donor" hair and placement of it through its cells in the balding area.

When you think about it, anti-andrognes and substances that supress particular dermal papilla growth inhibitors are simply attempts to keep nature from taking its course. Dietary changes to lower androgen levels in the dermis are very healthy for the rest of the body and thats why I support them, however if one is born with a tendency to baldness.............attempts to fight baldness short of real "gene" therapy that literally changes their genetics up there on their head are lifelong treatments.

Id rather be lucky like my uncles and have a full head of hair all my life and eat whatever I want, use harsh shampoos, and never think about my hair at all...........but that takes a change in genetics. Till then, we have to work a tad, much like an acne-prone kid has to wash his face more often and use some cream in a container to keep from breaking out vs. that kid across the street with perfect skin. Except baldness is worse.............its a lifelong fight that doesn't end a few years after puberty. Sucks doesn't it?

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