Prostaglandin Graphic

[Davey Jones]

I was just reading about the 5-lox inhibition for combating inflammation, and I noticed that the other side of the cascade for archidonic acid is the production of prostaglandins (like PGE2 and PGD2). I've been trying to wrap my head around the whole prostaglandins thing recently, and this helped get a handle on things. Figured I'd post it:



I also have a few questions, if anyone is already all read up anyway.

It is my understanding that your hair would benefit from an environment heavy on the PGE2 and light on the PGD2, or that's one of the newer theories at least. OC000459 is said to block PGD2. It is a CRTH2 antagonist. Problem is...CRTH2 is not on that graphic. Does anyone know by what mechanism OC000459 lowers PGD2?

Are we sure that OC000459 is the only safe chemical out that can lower PGD2? Is there nothing that will inhibit the actions of PGD synthase, perhaps, as lipoxygenase inhibitors can lower levels of leukotrienes?

Lastly which chemicals are out/on the horizon that can promote/act as PGE2?

P.S. I know that there are many theories behind hairloss. Some competing, some related, some ambiguously competing/related. However, in this thread, I'd like to just discuss prostaglandins and their mechanisms and potential relation to hairloss.

[2020]

It is my understanding that your hair would benefit from an environment heavy on the PGE2 and light on the PGD2, or that's one of the newer theories at least. OC000459 is said to block PGD2. It is a CRTH2 antagonist. Problem is...CRTH2 is not on that graphic. Does anyone know by what mechanism OC000459 lowers PGD2?

because CRTH2 is a receptor and because most people reference it as DP2

Are we sure that OC000459 is the only safe chemical out that can lower PGD2? Is there nothing that will inhibit the actions of PGD synthase, perhaps, as lipoxygenase inhibitors can lower levels of leukotrienes?

100% sure. The receptor itself - CRTH2 was only found recently so they haven't had enough time to come up with antagonists

Lastly which chemicals are out/on the horizon that can promote/act as PGE2?

minoxidil is one... you could also just buy a direct PGE2 analog but it's very expensive

[Davey Jones]

because CRTH2 is a receptor and because most people reference it as DP2

Ah, so it's a blocker-type thing. OC000459 binds to CRTH2, preventing PGD2 from binding? It doesn't actually lower levels of PGD2 then?

100% sure. The receptor itself - CRTH2 was only found recently so they haven't had enough time to come up with antagonists

So there is only one safe receptor antagonist, but I was wondering if there were any conversion inhibitors. Sorry, I'm not really sure what the scientific name for that kind of compound would be. I mean something that acts sort of like fin. Rather than binding to the androgen receptor site, it inhibits the actions of 5AR. Is there anything that inhibits PG2 synthase like fin inhibits 5AR or an AI inhibits aromatase?

minoxidil is one... you could also just buy a direct PGE2 analog but it's very expensive

Is that what that group buy you spoke of is for? I looked, and thought that was for OC000459. Maybe it was further on the page. I decided I needed to do a lot more readin' before I looked on that thread too much. I was getting a little lost.

So, in your opinion, would minoxidil be sufficient to regrow a nice amount of hair when coupled with OC000459? I know it would just be an educated guess at this point, I'm just wondering what you think.

[2020]

Ah, so it's a blocker-type thing. OC000459 binds to CRTH2, preventing PGD2 from binding? It doesn't actually lower levels of PGD2 then?

yes, prevents PGD2 from functioning and shrinking follicles. Actual levels of PGD2 will probably stay the same until we figure out a way to actually reverse this prostaglandin imbalance permanently

So there is only one safe receptor antagonist, but I was wondering if there were any conversion inhibitors. Sorry, I'm not really sure what the scientific name for that kind of compound would be. I mean something that acts sort of like fin. Rather than binding to the androgen receptor site, it inhibits the actions of 5AR. Is there anything that inhibits PG2 synthase like fin inhibits 5AR or an AI inhibits aromatase?

not yet I don't think so

Is that what that group buy you spoke of is for? I looked, and thought that was for OC000459. Maybe it was further on the page. I decided I needed to do a lot more readin' before I looked on that thread too much. I was getting a little lost.

So, in your opinion, would minoxidil be sufficient to regrow a nice amount of hair when coupled with OC000459? I know it would just be an educated guess at this point, I'm just wondering what you think.

not sure by how much minoxidil increases PGE2 I'll have to look it up but its natural levels in AGA scalp are not that much lower than normal so it's not that big of a problem... excess PGD2 is the main problem. Also, in that study they said that PGD2 is MUCH BETTER at inhibiting hair growth than PGE2/PGF2 is at growing hair....

I'm almost positive that PGE2 analog + CRTH2 antagonist will regrow all your hair but the problem is that you will have to use those treatments for life until we figure out how to fix the main problem - prostaglandin imbalance

[Gjm127]

Good thread.

[hairysituation]

This is the proactivity I'm encouraging other members to adapt as well! Great stuff! 2020, keep us updated on how the results turns out, ok?

[Davey Jones]

What method of delivery are you guys looking at? How is this going from a powder to something you put on your scalp?

As a sidenote, has anyone brought up the idea of using a derma-roller to increase absorbtion?

[Follicle Death Row]

I only know of resveratrol that you can buy. It was thought before to have some beneficial effect on hair but has never been quantified or confirmed. I take resveratrol as a supplement but I'm sure at that dose it does anything for the hair. It's quite expensive mind and I'm not specifically taking it for hair just general health. Might not even be worth taking. I believe the only supplement that we'd all really benefit from in terms of general health is vitamin d.

As for making a topical I'd have to look into it but I don't think I'd have the know how to actually make one.

[Follicle Death Row]

From my reading around systemic PGD2 synthase inhibitors would not be a good idea as apparently it's important for neuromodulation. So topicals it is.

[Follicle Death Row]

One other thing, the ideal topical would actually be a shampoo that would have 5AR inhibitory effects, along with androgen receptor blocking molecules. The second form of attack would be PGD2 synthase inhibitory effects and PGD2 receptor blockers of some kind. Attacking the problem at 4 distinct steps would stop signalling nearly completely. Of course hairloss may be even more complex still but to date this is all we know.

In a nutshell it would have to be a shampoo with 4 different molecules that can be absorbed locally. A big ask but not impossible.

[ferwin]

. The second form of attack would be PGD2 synthase inhibitory effects and PGD2 receptor blockers of some kind.

This could be one of the components you're looking for:


50% suppression of the PGD2 level by cetirizine

http://www.ncbi.nlm.nih.gov/m/pubmed/2469708/

ferwin

[CurlyBird]

One other thing, the ideal topical would actually be a shampoo that would have 5AR inhibitory effects, along with androgen receptor blocking molecules. The second form of attack would be PGD2 synthase inhibitory effects and PGD2 receptor blockers of some kind. Attacking the problem at 4 distinct steps would stop signalling nearly completely. Of course hairloss may be even more complex still but to date this is all we know.

In a nutshell it would have to be a shampoo with 4 different molecules that can be absorbed locally. A big ask but not impossible.

Unfortunately, there is research that shows topical finasteride is absorbed systemically. So a topical 5-AR inhibitor would not necessarily be preferable. And should it be a shampoo, it better be able to penetrate the scalp easily and quickly or else most of the ingredients will be washed off.

[rdawg]

Any companies looking into creating a full-market product for this.

and anyone have any actual experience/results with using a PGD2 inhibitor?

It seems like a very worthy thing to go through a trial for.

Wouldn't it essentially be Minoxidil mixed with a PGD2 inhibitor? super minoxidil.

[youngin]

So is everyone saying that the follicles CRTH2 receptor is uptaking PGD2 and causing the hair not to grow? If that's the case, then why do only the follicles on the top of our heads do it, not the sides? The same amount of PGD2 would be running through our blood to the sides of our head.

[gutted]

So is everyone saying that the follicles CRTH2 receptor is uptaking PGD2 and causing the hair not to grow? If that's the case, then why do only the follicles on the top of our heads do it, not the sides? The same amount of PGD2 would be running through our blood to the sides of our head.

some believe its because of "genetics"

feed the back and sides with a continuous supply of pgd2(dht), and the hairs would minutuarise too but this doesnt happen because blood and lymphatic circulation/drainage is good in this region.