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Pgd2 mph


#1

A prostaglandin d-synthase-positive mast cell gradient characterizes scalp patterning.

AuthorsLarson AR, et al. Show all Journal
J Cutan Pathol. 2013 Dec 19. doi: 10.1111/cup.12286. [Epub ahead of print]

Affiliation
Abstract
BACKGROUND: Pattern (androgenetic) alopecia is commonly encountered in scalp biopsies obtained for non-scarring hair loss. Prostaglandin d-synthase is known to be elevated in bald vs. non-alopetic scalp of patients with androgenetic alopecia. We hypothesized that this difference in pattern of prostaglandin d-synthase expression may constitute a developmental pattern inherent to normal as well as alopecic scalp skin, thus defining a ‘field’ vulnerable to acquired hair loss.

METHODS: We immunohistochemically mapped prostaglandin d-synthase expression from supra-auricular to vertex scalp skin of 11 cadavers.

RESULTS: We found significantly more dermal mast cells immunoreactive for prostaglandin d-synthase in the vertex compared to the lateral aspects of the scalp, with a decrement that spatially approximated the pattern of androgenetic alopecia. This difference was present in both balding and non-balding scalps and was independent of gender. Dual labeling established dermal cells expressing prostaglandin d-synthase as mast cells.

CONCLUSIONS: These data indicate that scalp is spatially programmed via mast cell prostaglandin d-synthase distribution in a manner reminiscent of the pattern seen in androgenetic alopecia.

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


#2

Wasn’t this discovered and patented by Cotsarelis already?

http://patentscope.wipo.int/search/en/detail.jsf?docId=WO2013142295&recNum=1&maxRec=&office=&prevFilter=&sortOption=&queryString=&tab=PCT+Biblio


#3

Thank you very much, shivers, for an excellent find.

I think this may be very significant.

For one thing, it kind of turns my previous understanding of the place of PGD2 on its head.

The previous consensus as that high PGD2 Synthase and PGD2 were a direct result of DHT. In other words, PGD2 was thought to be “downstream” of DHT.

But this result is showing that there is a “decrement” in PGD2 Synthase in Mast cells from the immediate supra-auricular region (right above the ear), to the vertex, and this is present in people with MPB and without MPB, in men and women. In other words, in everybody.

That, to me, would indicate a completely different cause-and-effect relationship between DHT and PGD2.

It looks like DHT is not causing increased PGD2 in those areas. Rather, those areas area already “primed” to lose hair because of their Mast cells naturally having high levels of PGD2 Synthase… and the presence of DHT in some people, combined with the already-existing high PGD2, triggers MPB in those areas.

A therapeutic strategy might still involve inhibiting or blocking PGD2 or PGD2 Synthase enzyme, however.

I would like to reread the results from Drs. Cotsarelis and Garza to see if there is anything in here which contradicts their findings. But I don’t think there are any huge contradictions.

Any other ideas?

By the way, the reason I haven’t been around here much for a while is because I feel that the very angry and insulting treatment of Dr. Nigam was like a lynch mob, and you can still feel the hate in here. It seems that since Dr. Nigam has left, all the members of the lynch mob have suddenly left too. But I have to say I’ve never seen anything like that before not just on HairSite but anywhere. I’m with Freddie555 on this. What happened here was brutal and sick, especially considering that Dr. Nigam is doing some real, valuable research that may benefit us all.


#4

What kind of a therapeutic strategy may be,Roger_that? I am sure you have an idea.


#5

Excellent post Shivers and response Roger.

Regarding Nigam, i too was thoroughly disgusted with the brainless lynch mob mentality exercised while he was here. Im just about to book in with Patrick Mwamba who is collaberating with Nigam and (in print) has only good things to say about the man and the important knowledge he has to impart.
I will be sure to discuss this with him as thoroughly as he will allow and post the gist of our convo here.


#6

delete


#7

Remember that Cotsarelis/Garza’s conclusion was that PG’s regulate hair growth; so, of course dermal mast cells which are immunoreactive for prostaglandin d-synthase will appear in all hair. This study shows that on certain areas eg crown, it is more immunoreactive which explains why there is patterning to MPB. This add more respect to the hypothesis of Cotsarelis/Garza that a overproduction of PGD2 is the cause of MPB. Why there is a overproduction is unknown(could be related to DHT etc), but it doesnt matter as long as they can fix it.

I Cant wait for the clinical trials to start!


#8

[quote][postedby]Originally Posted by roger_that[/postedby]
The previous consensus as that high PGD2 Synthase and PGD2 were a direct result of DHT. In other words, PGD2 was thought to be “downstream” of DHT.[/quote]

Couldn’t they still be? Everyone may have a gradient, but the absolute levels of PGD2 could still be upregulated by DHT.

PS. there goes the gravity theory for patterning :stuck_out_tongue:


#9

Yes, it’s possible, but (and I hate to base so many arguments on this) the Occam’s Razor rule would say that is unnecessary to seeing a role for DHT here. It’s not like they said there is a gradient, but it’s more pronounced in people with MPB. They just said there’s a gradient in everyone, period.

Therefore DHT may play a different role in conjunction with the increased MPB in those areas.

Very interesting stuff, and I think there’s a lot more to explore here.

Yes, I think you’re right there. This would definitely tend to strongly refute Dr. Ustuner’s “gravity” theory.


#10

RT, glad to see you posting again. Wondered whether we would after that last uncalled for deletion
of your post.

I hope you guys are right about this data defeating Dr. U’s theory. Here’s the conclusion:

CONCLUSIONS: These data indicate that scalp is spatially programmed via mast cell
prostaglandin d-synthase distribution in a manner reminiscent of the pattern seen in
androgenetic alopecia.

Would the age of the cadavers matter in reaching this conclusion? And in necessarily
defeating Dr. Ustuner’s theory? (ie., someone who’s been walking around for 12 years as
opposed to 60). Thanks


#11

there is something to Dr Cots theory. I have stopped shedding with Indomethacin and Chromoglycate and in 20 years of balding nothing has even slowed my hair loss until this PDG2 inhibitors


#12

[quote][postedby]Originally Posted by roger_that[/postedby]
Thank you very much, shivers, for an excellent find.

I think this may be very significant.

For one thing, it kind of turns my previous understanding of the place of PGD2 on its head.

The previous consensus as that high PGD2 Synthase and PGD2 were a direct result of DHT. In other words, PGD2 was thought to be “downstream” of DHT.

But this result is showing that there is a “decrement” in PGD2 Synthase in Mast cells from the immediate supra-auricular region (right above the ear), to the vertex, and this is present in people with MPB and without MPB, in men and women. In other words, in everybody.

That, to me, would indicate a completely different cause-and-effect relationship between DHT and PGD2.

I agree. If you don’t have something good to say, then say nothing!!
It would help if we had a moderator for this site.

It looks like DHT is not causing increased PGD2 in those areas. Rather, those areas area already “primed” to lose hair because of their Mast cells naturally having high levels of PGD2 Synthase… and the presence of DHT in some people, combined with the already-existing high PGD2, triggers MPB in those areas.

A therapeutic strategy might still involve inhibiting or blocking PGD2 or PGD2 Synthase enzyme, however.

I would like to reread the results from Drs. Cotsarelis and Garza to see if there is anything in here which contradicts their findings. But I don’t think there are any huge contradictions.

Any other ideas?

By the way, the reason I haven’t been around here much for a while is because I feel that the very angry and insulting treatment of Dr. Nigam was like a lynch mob, and you can still feel the hate in here. It seems that since Dr. Nigam has left, all the members of the lynch mob have suddenly left too. But I have to say I’ve never seen anything like that before not just on HairSite but anywhere. I’m with Freddie555 on this. What happened here was brutal and sick, especially considering that Dr. Nigam is doing some real, valuable research that may benefit us all.[/quote]


#13

[quote][postedby]Originally Posted by ESP2[/postedby]
RT, glad to see you posting again. Wondered whether we would after that last uncalled for deletion
of your post.

I hope you guys are right about this data defeating Dr. U’s theory. Here’s the conclusion:

CONCLUSIONS: These data indicate that scalp is spatially programmed via mast cell
prostaglandin d-synthase distribution in a manner reminiscent of the pattern seen in
androgenetic alopecia.

Would the age of the cadavers matter in reaching this conclusion? And in necessarily
defeating Dr. Ustuner’s theory? (ie., someone who’s been walking around for 12 years as
opposed to 60). Thanks[/quote]

Thanks, ESP2.

How does this affect Dr. Ustuner’s theory?

I think it makes it even less likely to be true than we thought when we didn’t know this.

As you said, this finding suggests that there’s an inherent biological or phsyiological reason for the patterning. The study suggests that underlying cause is present in EVERYONE, male or female, bald or not bald.

It would then somehow involve DHT to trigger expression of MPB in these areas. Maybe the patterning template is slightly different, more diffusely spread over the scalp, and with a less severe gradient in PGD2 Synthase, in women, which would result in female pattern baldness looking a bit different than MPB.

As far as Dr. Ustuner’s theory, you know I didn’t like it from the start.

BUT, I can see one situation where his theory may, in part, be true – and that still wouldn’t contradict these findings about the PGD2 Synthase gradient.

Suppose that gravity CAUSES the gradient in the first place.

Then, since everyone stands upright (just about) and everyone is subject to the same gravity, the same gradient would exist in everyone.

In that case, it still wouldn’t change our approach to therapy one bit. It is inconsequential.

Because, what can you practically do to counteract the effects of gravity on the scalp? Have everyone who’s balding hang upside down for 12 hours a day?

That would be the ONLY approach to take, and it isn’t practical.

If gravity is causing the PGD2 gradient, then there’s still a PGD2 gradient that you can attack. You can also attack PGD2 or PGD2 Synthase in conjunction with going after DHT and other things.

So Ustuner’s theory is, at best, moot.


#14

when do trials start?


#15

[quote][postedby]Originally Posted by alecbaldone[/postedby]
when do trials start?[/quote]
Should be this year. It was March 2012 when he said “within 2 years”, hopefully there will be an update sometime soon.


#16

BUT, I can see one situation where his theory may, in part, be true – and that still wouldn’t contradict these findings about the PGD2 Synthase gradient.

Suppose that gravity CAUSES the gradient in the first place.


If gravity is causing the PGD2 gradient, then there’s still a PGD2 gradient that you can attack. You can also attack PGD2 or PGD2 Synthase in conjunction with going after DHT and other things.

So Ustuner’s theory is, at best, moot.[/quote]

I like your analysis–this is exactly what I was driving at: the possibility that gravity may (directly or indirectly) be responsible for the gradient.
I quibble with the conclusion that every human scalp is programmed to distribute PGD2 in a manner consistent with MPB, because the
while the study found the distribution pattern to be present–I think it’s a leap for it to conclude we are all programmed that way (I didn’t see anything
that supported that conclusion).

Also, while I hope you are proven right, I’m not sure Dr. U’s theory is moot unless and until any conceivable attack methods prove successful at restoring lost hair…


#17

[quote]I quibble with the conclusion that every human scalp is programmed to distribute PGD2 in a manner consistent with MPB, because the
while the study found the distribution pattern to be present–I think it’s a leap for it to conclude we are all programmed that way (I didn’t see anything
that supported that conclusion).[/quote]

Why not? The gradient itself supports the conclusion that we’re all programmed that way. The same type of gradient or decrement in PGD2 Synthase was found in all cadavers, male and female, bald and non-bald.

Besides, there are plenty of ways our bodies are programmed to create different types of phenotypic outcomes. Everything from the color of our hair and eyes, to the age and pattern our hair goes gray, to whether we come down with a genetic disease, are all programmed by genetics. Why couldn’t this one be, too? Because you don’t see it? A person may have genes for colon cancer or breast cancer, and they don’t see it or know it, until the genes are expressed.

The very pattern of hair growth on the human scalp, ending at a hairline above the forehead, and ending above the ears and the neck, indicates that boundaries of hairy areas can be patterned by genes.

What I meant by Dr. U’s theory being moot is that even if it is true (and to me, there’s little chance it is true), it would be moot.

The reason I think it would be moot is that you have a physical cause being translated into a biochemical state.

Obviously we cannot do anything about the physical cause because we all have to stand and walk upright.

But (assuming Dr. U’s theory is true), that physical cause works by being translated into a biochemical state.

We know that we can use drugs (or cell therapy) to impact or change a biochemical state.

So, what’s the problem? If Dr. Ustuner’s theory happens to be true, there is something we can do. In fact, treating MPB if his theory is true would be no different than treating MPB if it isn’t true, because the physical cause (the gravity) is translated into a biochemical state that can be attacked.

Let’s assume his theory is true (a special case). What we know now (undisputed) is that there’s something going on with PGD2 in the scalp. We also know that the scalps of people with MPB are biochemically different than those without MPB, in terms of prostaglandins, DHT, etc. From that, we can infer (a strong inference) that if Dr. U’s theory is true, the physical cause (gravity) acts by altering the biochemical state in affected people.

Therefore, since we know there’s an altered biochemical state in people with MPB, how would Dr. Ustuner’s theory being true mean that we couldn’t use drugs to change or reverse that altered biochemical state?


#18

[quote]I quibble with the conclusion that every human scalp is programmed to distribute PGD2 in a manner consistent with MPB, because the
while the study found the distribution pattern to be present–I think it’s a leap for it to conclude we are all programmed that way (I didn’t see anything
that supported that conclusion).

[postedby]Originally Posted by roger_that[/postedby]

Why not? The gradient itself supports the conclusion that we’re all programmed that way. The same type of gradient or decrement in PGD2 Synthase was found in all cadavers, male and female, bald and non-bald.

Besides, there are plenty of ways our bodies are programmed to create different types of phenotypic outcomes. Everything from the color of our hair and eyes, to the age and pattern our hair goes gray, to whether we come down with a genetic disease, are all programmed by genetics. Why couldn’t this one be, too? Because you don’t see it? A person may have genes for colon cancer or breast cancer, and they don’t see it or know it, until the genes are expressed.

The very pattern of hair growth on the human scalp, ending at a hairline above the forehead, and ending above the ears and the neck, indicates that boundaries of hairy areas can be patterned by genes. [/quote]

(Sorry for the delay getting back)

This is why I question the age of the cadavers. Assuming they were all of elderly people, the gradient might only
support the conclusion that we all end up that way; however, if there were some very young cadavers involved
in the study that also exhibited the gradient, I’d agree–we’re programmed that way. As written, the conclusion appears
to be based on circumstantial evidence (albeit, very convincing).

[postedby]Originally Posted by roger_that[/postedby]

[quote] What I meant by Dr. U’s theory being moot is that even if it is true (and to me, there’s little chance it is true), it would be moot.

The reason I think it would be moot is that you have a physical cause being translated into a biochemical state.

Obviously we cannot do anything about the physical cause because we all have to stand and walk upright.

But (assuming Dr. U’s theory is true), that physical cause works by being translated into a biochemical state.

We know that we can use drugs (or cell therapy) to impact or change a biochemical state.

So, what’s the problem? If Dr. Ustuner’s theory happens to be true, there is something we can do. In fact, treating MPB if his theory is true would be no different than treating MPB if it isn’t true, because the physical cause (the gravity) is translated into a biochemical state that can be attacked.

Let’s assume his theory is true (a special case). What we know now (undisputed) is that there’s something going on with PGD2 in the scalp. We also know that the scalps of people with MPB are biochemically different than those without MPB, in terms of prostaglandins, DHT, etc. From that, we can infer (a strong inference) that if Dr. U’s theory is true, the physical cause (gravity) acts by altering the biochemical state in affected people.

Therefore, since we know there’s an altered biochemical state in people with MPB, how would Dr. Ustuner’s theory being true mean that we couldn’t use drugs to change or reverse that altered biochemical state?[/quote]

While, in theory, I agree with you, we all know that so far, mankind is 0 for infinity when it comes to applying drugs that restore hair (fully).
Perhaps now that I’m moving into middle age and balder/shinier by the year, I may be seeing the glass has half-empty, instead of half-full,
or it could be failure after failure by numerous bio-chem & pharma co’s, but I find that subscribing to a theory that says “nothing works until proven
differently” is more comfortable than “this will work if tried.”