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New study...................hairloss is in dermal papilla


#1

1: Br J Dermatol. 2006 Apr;154(4):609-18. Links
Inhibitory autocrine factors produced by the mesenchyme-derived hair follicle dermal papilla may be a key to male pattern baldness.Hamada K, Randall VA.
Department of Biomedical Sciences, University of Bradford, Bradford BD7 1DP, UK.

BACKGROUND: Androgenetic alopecia, or male pattern baldness, is a common, progressive disorder where large, terminal scalp hairs are gradually replaced by smaller hairs in precise patterns until only tiny vellus hairs remain. This balding can cause a marked reduction in the quality of life. Although these changes are driven by androgens, most molecular mechanisms are unknown, limiting available treatments. The mesenchyme-derived dermal papilla at the base of the mainly epithelial hair follicle controls the type of hair produced and is probably the site through which androgens act on follicle cells by altering the regulatory paracrine factors produced by dermal papilla cells. During changes in hair size the relationship between the hair and dermal papilla size remains constant, with alterations in both dermal papilla volume and cell number. This suggests that alterations within the dermal papilla itself play a key role in altering hair size in response to androgens. Cultured dermal papilla cells offer a useful model system to investigate this as they promote new hair growth in vivo, retain characteristics in vitro which reflect their parent follicle’s response to androgens in vivo and secrete mitogenic factors for dermal papilla cells and keratinocytes. OBJECTIVES: To investigate whether cultured dermal papilla cells from balding follicles secrete altered amounts/types of mitogenic factors for dermal papilla cells than those from larger, normal follicles. We also aimed to determine whether rodent cells would recognize mitogenic signals from human cells in vitro and whether factors produced by balding dermal papilla cells could alter the start of a new mouse hair cycle in vivo. METHODS: Dermal papilla cells were cultured from normal, balding and almost clinically normal areas of balding scalps and their ability to produce mitogenic factors compared using both human and rat whisker dermal papilla cells as in vitro targets and mouse hair growth in vivo. RESULTS: Normal scalp cells produced soluble factors which stimulated the growth of both human scalp and rat whisker dermal papilla cells in vitro, demonstrating dose-responsive mitogenic capability across species. Although balding cells stimulated some growth, this was much reduced and they also secreted inhibitory factor(s). Balding cell media also delayed new hair growth when injected into mice. CONCLUSIONS: Human balding dermal papilla cells secrete inhibitory factors which affect the growth of both human and rodent dermal papilla cells and factors which delay the onset of anagen in mice in vivo. These inhibitory factor(s) probably cause the formation of smaller dermal papillae and smaller hairs in male pattern baldness. Identification of such factor(s) could lead to novel therapeutic approaches.

PMID: 16536801 [PubMed - indexed for MEDLINE]

Its in the papilla guys.

Inhibit TGF-beta (apple proanthocyandins) and DKK-1 probably is a good place to start. All the inflammation and other things are downstream of this.


#2

Interesting study! How would one inhibit DKK-1?


#3

» Interesting study! How would one inhibit DKK-1?

Ive performed some fruitless web searches via google looking for “DKK-1 inhibitor” or “inhibited DKK-1” etc. DKK-1 was the second most upregulated gene in balding follicles or balding scalp (I forget which). It was upped even more than TGF-beta was. DKK-1 was shown to kill keratinocyte cells.

After reading about the apoptosis in K-cells, I kinda formulated my own idea about what might be happening in baldness. We know that the first inflammation in baldness is seen at the infidulum, or opening in the dermis where the hair comes out of the skin. Well, it stands to reason that this is where alot of the dead keratinocyte cells would be…hanging onto the hair shaft while leaving the body, yet still in the body. Hyperkeratinization is involved with other autoimmune disorders. Perhaps the dead cells that are still in the body is what the travelling T-cells first recognize in the body and begin to attack. We now know that prostaglandin D2 is severely upregulated in balding scalp also, but I haven’t read anywhere that the dermal papilla can make prostaglandin D2, and it would then seem to be part of the immunological response. TGF-beta is associated with fibrosis and is also a negative growth factor identified and released by the dermal papilla. I’d bet that TGF-beta and DKK-1 are going to be found to be two of the most if not the most important negative growth factors the dermal papilla makes in Androgenic Alopecia. We have seen how well hair grows when TGF-beta is blocked in the apple poly photos and mouse pictures.

I think whatever the immune system is attacking, its downstream of what is released in the dermal papilla cells. Hair transplants kinda “prove” this in my opinion as Ive seen so many HT’s that have been around since the eighties and the donor hair is growing in balded scalp just fine after nearly thirty years.


#4

I’m reluctant to say this for sure but all this evidence kinda shows that intercytex might really be trying something that has potential to give us a head of dht resistant hair.


#5

Yeah, that’s how it sounds to me too.

The bottom line is that if they can get viable donor-area DP cells to start doing their job in balding follicles, then we’ve got real HM on our hands.

I would rather just pay the huge money and have that kind of no-maintinence solution for life. It beats any amount of daily topical regimens, no matter how effective the more advanced topicals eventually might be.


#6

There is no doubt in my mind that the philosophy behind Intercytex work is tremendously outstanding but everything relies on finding a good working protocol…Benji would you please clarify to me that Prostaglandins inhibition issue please !


#7

» Benji would you please clarify to me that Prostaglandins
» inhibition issue please !

What about prostagladins did you want to know?

Here is what I know about them. Latanaprost inhibits something like three of them, and nizoral inhibits a couple of them. Both grow hair.

Not all prostaglandins are bad.

Costarialis’ patent calls for the inhibition of the particular prostaglandin, PGD2 or prostaglandin D2. Its not one of the prostaglandins that Niz or Latanaprost inhibits.

In blood platlets, ECGC from green tea inhibits Prostaglandin D2…but Im not certain that translates to the human scalp.

I do know (now) that there is a prostaglandin D2 receptor on the hair follicle thanks to a guy named Harold at HLT. Prostaglandin D2 was found to be severely increased in balding scalp, and application of PGD2 could delay the next anagen phase in mice indefinitely after depilation of their fur. PGD2 is formulated downstream of COX-2…so topical COX-2 inhibitors might be helpful in lessening this substance. A few COX-2 inhibitors Ive read about were rosemary and sage and thyme and aspirin, and ibuprofen, and caffeine. Who knows, maybe these things are helpful from the anti-inflammation standpoint.

ICX getting us donor resistant hair would be the best thing by far in my opinion. Then we could pretty much forget about it.


#8

Dear benji,

You are getting somehow a bit obsessed about ICX aint you !! :smiley:

Anyway studies showed that the balding spots have 4.4 times more adrongens then healthy hair scalp …or am I connfusing things and that was 4.4 more Prostaglandins ??

Prostaglandins are fatty acids-derives right ! I guess you are fully aware that unsaturated fatty acids have pretty good androgenic inhibition capabilities …what do you have to say about that !

Also do you have any insights about the way Prostaglandins contribute to AGA ?!


#9

The study showed that there was much more prostaglandin D2 in balding scalp. There is also more DHT in balding scalp, but even DHT isn’t as upregulated as prostaglandin D2 is. There is a prostaglandin D2 receptor on hair follicles. It appears to be important in the inflammation and oxidative stress put on the follicle.

Prostaglandins are downstream of COX-2 (and I think one or two of them are downstream of COX-1). Both COX’s are downstream of arachidonic acid. Topical anti-inflammaotries might inhibit these to some extent, but probably not totally.

The patent called for a prostaglandin-D2 inhibtor at the recptor site, or in its synthesis—anything to get it out of the scalp. The thing is…some prostaglandins are good for hair, most apparently are not.

Ketoconazole inhibits two or three prostaglandins and latanaprost inhibts three of them.


#10

I’m now considering to try Ginger (I 've it both powder and roots)…I stil have to choose the vehicle and whether I’m gonna take it topically or internally