Re: A recently discovered new factor in AA, the cure is near 
Hey all,
Havent posted in a long time as i generally havent focussed much on hairloss and related issues in a few years. Was very interested to do a pubmed search to see if anything new had happened research wise and to see that this result had finally been published and has caused a big ruckus. To give some perspective this was something some people were talking about here over 4 years ago thanks to the miracle of online patents:
viewtopic.php?f=32&t=43715&p=412209&hilit=+pgd2#p412209
Its funny because around the same time Cotsarelis filed the patent on that whole wnt wounding thing that became the basis of Follica and that kind of swept this PGD2 thing aside. The PGD2 synthase elevation always seemed very dramatic and very well demonstrated in the info we had from the patent but as time went by and the results were never published it sort of became a secondary thing - it was only one set of unpublished findings from one group after all, who seemed set on pursuing a treatment based on other findings commercially. Still there were other hints that it might be really important such as hte effect of PGF2 analogs like latanorast on hair growth and the fact that mice which overexpressed COX-2 in skin developed hair miniaturization (an important point because hair miniaturization, not just hair loss, is a defining characteristic of male pattern baldness) and enlarged sebaceous glands.
http://www.pnas.org/content/98/13/7629.figures-only
Anyway some thoughts:
Basically:
Arachidonic Acid -- COX1/COX2--> Prostaglandin H2 --PG D Synthase --> PGD2 <binds to> PGD2 receptor
In this case the PGD synthase is apparently the PTGDS "lipocalin type" that is commonly found in the brain and not the PGDS type associated with mast cells. IN male pattern baldness it seems that something downstream of androgens upregulates this PTGDS and thats why we are getting so much PGD2 unlike in the mice where it was COX2 being upregulated and a whole host of prostaglandins being overexpressed. As mentioned the PGD2 receptor involved here is CTRH2.
So it seems we have 3 targets:
1) COX1/COX2 - lower all prostaglandin production
2) PTGDS - lower PGD2 production
3) CTRH2 - stop PGD2 from binding.
In terms of 2) and 3) I'm not sure that there is a lot we can do by ourselves. Indomethicain is a weak antagonist of CTRH2. Selenium Chloride (SeCl4) and sodium selenite (Na2SeO3) are inhibitors of PTGDS but from what i gather you wouldnt want to mess with selenium chloride at least. OTOH of course the commonly available NSAIDs like aspirin/ibuprofen/paracetemol are COX1/2 inhibitors. Still i havent come up with much research in terms of how to effectively apply them topically and how effective they might be.Theres also a bit about flavonoids like luteolin and quercetin interfering with PGD2 production but its not clear on the pathways involved (it may be more relevant to the PGDS pathway) but some of it at least appears to be COX related.
