New minoxidil study............how it works being discovered

[michael barry]

Posted: Sun Dec 31, 2006 2:53 pm Post subject:

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Here is a new study about how exactly minoxidil works, read and learn young'un's.



Hair growth effect of minoxidil]

[Article in Japanese]

Otomo S.

Pharmacological Evaluation Laboratory, Taisho Pharmaceutical Co., Ltd., 403, Yoshino-cho 1-chome, Saitama-shi, Saitama 330-8530, Japan.

The length and size of hair are depend on the anagen term in its hair cycle. It has been reported that the some cell growth factors, such as VEGF, FGF-5S, IGF-1 and KGF, induce the proliferation of cells in the matrix, dermal papilla and dermal papillary vascular system and increase the amount of extra cellular matrix in dermal papilla and then maintain follicles in the anagen phase. On the other hand, negative factors, like FGF-5, thrombospondin, or still unknown ones, terminate the anagen phase. If the negative factors become dominant against cell proliferation factors according to fulfilling some time set by the biological clock for hair follicles, TGF beta induced in the matrix tissues evokes apoptosis of matrix cells and shifts the follicles from anagen to catagen. Androgenetic alopecia is caused by miniaturizing of hair follicles located in the frontal or crown part of scalp and are hereditarily more sensitive to androgen. In their hair cycles, the androgen shortens the anagen phase of follicles and shifts them to the catagen phase earlier than usual. The mode of action of hair growth effect of minoxidil is not completely elucidated, but the most plausible explanation proposed here is that minoxidil works as a sulfonylurea receptor (SUR) activator and prolongs the anagen phase of hair follicles in the following manner: minoxidil (1) induces cell growth factors such as VEGF, HGF, IGF-1 and potentiates HGF and IGF-1 actions by the activation of uncoupled SUR on the plasma membrane of dermal papilla cells, (2) inhibits of TGF beta induced apoptosis of hair matrix cells by opening the Kir 6.0 channel pore coupled with SUR on the mitochondrial inner membrane, and (3) dilates hair follicle arteries and increases blood flow in dermal papilla by opening the Kir 6.0 channel pore coupled with SUR on the plasma membrane of vascular smooth muscle cells



Obviously minoxidil is much more than just a "growth stimulant'


Read that paragraph twice and think about it, it reveals quite alot about baldness and the negative growth factors released by the dermal papilla's in men with baldess. The big three are popular for a reason. Its because they work.

 

[Bryan]

Obviously minoxidil is much more than just a "growth stimulant'

Why do you feel that way, Michael?

Bryan

 

[michael barry]

Bryan,


The authors wrote: ".......but the most plausible explanation proposed here is that minoxidil works as a sulfonylurea receptor (SUR) activator and prolongs the anagen phase of hair follicles in the following manner: minoxidil (1) induces cell growth factors such as VEGF, HGF, IGF-1 and potentiates HGF and IGF-1 actions by the activation of uncoupled SUR on the plasma membrane of dermal papilla cells, (2) inhibits of TGF beta induced apoptosis of hair matrix cells by opening the Kir 6.0 channel pore coupled with SUR on the mitochondrial inner membrane, and (3) dilates hair follicle arteries and increases blood flow in dermal papilla by opening the Kir 6.0 channel pore coupled with SUR on the plasma membrane of vascular smooth muscle cells "


It appears that minoxidil: counteracts TGF-beta to some extent, and this probably leads to less collagen getting deposited around the follicle which makes it hard for microcapillaries to reach it.

It also appears minoxidil opens potassium channels which help cellular communication in follicle cells.

It also appears that minoxidil dialates hair follicles arteries and increases papilla blood flow.

It also appears in other literature that minoxidil fights the hardening and crosslinking of collagen fibers in the connective tissue sheath and root sheath like aminexil also supposedly does

It also appears that minoxidil induces cell growth factors such as VEGF, HGF, IGF-1 and potentiates HGF and IGF-1 actions by the activation of uncoupled SUR on the plasma membrane of dermal papilla cells.......



Thats a hell of an effect on hair isnt it? Keratinocyte growth factor might be "just a stimulant", but minoxidil appears to do so much thats good for affected head hair in AA, its hard to just say its a plain ol' hypertrichotic isn't it? It may not fight baldness on as many fronts as prox-n, but for the price its a hell of a tool for young guys looking to hold onto what they have in my opinion.



By the way...........I looked around a tad and couldn't find anything that supposedly counteracts FGF-5 and thrombo-whatever, which are listed as negative growth factors released by papilla cells to other hair cells.



Bryan, Im of the opinion that when we find exactly what the papilla releases to the rest of the follicle we will be in the business of attempting to counteract baldness at that level. Men without baldness have androgen receptors and DHT, but their papillas must do something different. Counteracting THAT, with no need to alter hormones in anyway, would be the most elegant solution to baldness "someday" in my opinion.

 

[So]

Michael,

What is the difficulty associated with finding out exactly what the papilla releases to the rest of the hair follicle?

Is there great complexity in determining this? Has it been attempted before? How would you even go about the process in theory?

I am interested to know because as you put it someday it may be an elegant solution to baldness rather than screwing with our hormones.

 

[michael barry]

So,

I'd imagine we would be talking about very intricate lab work with extremely small volumes of subtances. Hair follicles can exist outside the bod for about fourteen days in a test tube while scientist overexpress androgen receptors on the dermal papillas (receptor expression is apparently decreased during the ex vivo cultivation and has to be made up for). Feed DHT to the test tube, and at the end of ten or twelve days, remove the follicle and see what substances can be identified within various follicle cells.

We aren't talking about a long part of the hair, just the little bulb and a few parts north of it. Thats the problem. THis is so SMALL. Finding out what every chemical is therein (without destroying them!) is probably a martyrs task. It would seem if all the chemicals could be identified first, then each could be added to various hair cells (keratinocyte cells, epidermal cells, root sheath, dermal sheath, papilla, etc) to see if the new substances slow any cell division down and thus prove to be negative growth factors. They mention two FGF-5, and thrombo-whatever as two that are negative.


I think haircloning will be here before they find out exactly what goes on in baldness.

And furthermore, even if we find out all the growth inhibitors and even find out which one or ones cause an immuno response................we still may not be able to find or synthesize anything that counteracts them as a topical or internal effectively and without dangerous side effects, etc.


I really wish a great topical receptor blocker that was effective for about thirty good hours with no sides could be synthesized by some pharma or another. That would seemingly be the best hope in the shorter term to help men keep what they have up there.

 

[Guest]

hi there So,, how are you progressing if any?

 

[So]

Michael,

Thanks!

I do not doubt the fact as you said that hair clonning will arrive before we know exactly how the balding process truely works.

Despite the difficulty (by way of size) associated with researching exactly what the papilla releases, I would have thought by now, someone would have prioritized it's importance as critical.

I am only taking a guess at best whilst stated the bluntly obvious but such pieces of information could reveal so much to the cause.

It seems like a backward approach.


Fight4Hairs,

Hi, I have made no progress with my current treatment regimen and my situation worsens as time goes by.

Although my loss is highly aggressive I do however remain optimistic in times of distress.

Whilst the blueprint for hair loss may be genetic, it is our cells in which dictate which blueprints (genes) to read and our environment in which influences our cells.

PM me to learn more if I have confused you mate
:?

 

[sammy]

hi,

nice reading, hope to hear more updates.