Cotsarelis/Garza Genetic analysis

[Boldy]

Its true that the dermal papilla over expresses androgen receptorss/ more sensitive for androgens. There it all starts. Pgd2 has huage impacts oh hair growth/ and proliferation of the cells.

in short, the pgd2 is responsible for androgen inducedDkk1(that is a WNT inhibitor), induces p53, tgfb, that triggers caspase apoptosis, and yet again dkk1, its and anti angiogenesis factor. Pge2|(the down regulated prostaglandin in AGA), is Pro angiogenesis, induces CD43+, wnt pathway, and FGF9.

this inbalance causes the hair to shrink, so not directly Androgens it self, but the triggered chain reaction behind it.

Check this topic for more detials: http://www.hairlosshelp.com/forums/m...hreadid=103373

Boldy

[UK_]

Pgd2 is just a result of the damage caused to the follicle by DHT.

PGD2 is always present in the wound healing process during the latter stages while PGE2 is present during the initial stages.

They're not causes of hair loss, they're just present because androgens have damaged the hair follicle, I think it has more to do with the pathway to regeneration, PGD2 is somehow inhibiting the regeneration of the hair follicle after it has become damaged, this is why Dr Cots is looking at both the regeneration (FGF9) pathway and also the inhibition to regeneration (PGD2) pathway.

[KO1]

Yep.


Keratin 15(KRT15, Red) a keratinocyte stem cell marker, labels a separate population than that
of the Prostaglandin D2 Synthase (PTGDS, Green) in the apoptotic hair follicle.

[HairlossAt15]

More details on on the effects of pgd2(aka agonism of gpr44) on human hair:

"To test the effect of PGD2 on human hair growth, we used explanted human hair follicles maintained in culture for 7 days. We added increasing amounts (from 0 to 10 μM) of PGD2, 15-dPGJ2, or vehicle to the culture medium and measured hair length (Fig. 6D). Starting at 5 μM, PGD2 and 15-dPGJ2 significantly inhibited hair growth. At 10 μM, PGD2-treated hair was 62 ± 5% shorter than vehicle, whereas 10 μM 15-dPGJ2 completely inhibited all hair growth. We tested a variety of other PGD2 analogs and found them to be capable of inhibiting hair lengthening. Agonism for GPR44 correlated with the ability to inhibit hair lengthening (fig. S3)."

pgd2 = 62% inhibition and 15-dPGJ2 = 100% inhibition. Both work through the gpr44 receptor. Thats a lot of inhibition!

Some evidence pgd2 may target progenitor cells:
"Both DP-1 and DP-2(gpr44) have been reported to be expressed by outer root sheath keratinocytes in the hair follicle, among other sites"

I noted earlier pdg2 was not found around the bulge/stem("mother")cells which might explain preservation of stem cells in AGA.

[KO1]

That's very interesting he thinks PGD2 is responsible for that. I agree they're after getting terminal growth, but I just found it striking that their primary endpoint for the trials were to generate neogenic-like hair follicles.

My wild guess is that perhaps other agents will be used on top of lithium to get terminal hairs.

[HairlossAt15]

^What did the Cots say to you?

What it appears to me is that Follica does not expect to grow terminal hairs in scalp, but rather "neogenic-like follicles" which are smaller than vellus. How those become terminal, I have no idea.

There long term goal is to certainly grow real hairs. I asked him if he thinks pdg2 is responsible for stopping the conversion of stem cells to progenitor cells and he said "that is our working hypothesis".

[Thinning87]

Thanks bro!

Please share with us if he replies!

^What did the Cots say to you?

What it appears to me is that Follica does not expect to grow terminal hairs in scalp, but rather "neogenic-like follicles" which are smaller than vellus. How those become terminal, I have no idea.

Well I'm sure their goal is to achieve cosmetic results...

[KO1]

^What did the Cots say to you?

What it appears to me is that Follica does not expect to grow terminal hairs in scalp, but rather "neogenic-like follicles" which are smaller than vellus. How those become terminal, I have no idea.

[ar50]

Here is his email: cotsarel@mail.med.upenn.edu

He has replied to me before but no guarantees.

Thanks bro!

[HairlossAt15]

Hey guys.

I wondered if one of us know how to contact dr. Cotsarelis, or his colleagues?
Maybe if we can get a hold and this guy ans his colleagus, we could get more info.

Greetings

AR

Here is his email: cotsarel@mail.med.upenn.edu

He has replied to me before but no guarantees.

[ar50]

Hey guys.

I wondered if one of us know how to contact dr. Cotsarelis, or his colleagues?
Maybe if we can get a hold and this guy ans his colleagus, we could get more info.

Greetings

AR

[KO1]

ehm thanks for the explanation but you can try it first

I would, I'm just tired and lazy at this point.

[KO1]

Lithium causes hair loss , but Follica used it in P2 trials. Point is, let's not generalize.

[Pentarou]

Alright, listen.

What is this business about Doxycycline upregulating FHF or whatever? I swear they tried to give me Doxy for acne as an anti-bacterial.

I did research, and of causes hair loss. I literally have the pills, never taken for this reason, right here.



Look it up. Doxy causes hair loss. I don't understand.

A drug applied topically may have completely different effects to the same drug being rconsumed orally.

[HairlossAt15]

More on deactivated bulge/stem cells:
Cotsarelis Interview:
" After a variety of confir-
matory tests,they were able to conclude that
“loss of this CD200hiITGA6hi population in
AGA represents a loss of activated bulge
cells.” These were not the quiescent stem
cells,but the progenitor cells responsible for
the immediate growth of new hair."

So these cells are needed for activation of the bulge(stem cells). Transfer of these cells is mentioned in his patent, as well as analogues of these cells. Perhaps pdg2 targets these cells as pdg2 is found at high levels at the secondary germ which i believe is were the CD200hiITGA6hiare located.

Now I am beginning to understand why Cotsarelis focuses so much on pdg2 when there were other genes involved as well. Either way more reason to be excited.