Hair Loss Forum - PGD2 linked to DHT - and how to reverse hair loss
instant hair thickening fibers scalp pigmentation tattoo

Log in | User | Register

Thread view  Order  «  
 

featured hair transplant results & topics
free hair transplant consultations in London, Los Angeles, New York, and cities worldwide

-Dr. Baubac (Alvi Armani) patient photo shoot.
-Hasson & Wong: 4050 grafts, 1 year, strip.
-Hairman2's 2500 grafts FUE at HDC Cyprus.

-Dr. Baubac (Alvi Armani): 8151 grafts FUE on a NW6.
-Dr. Ray Woods: world's 1st FUE + BHT scar repair!

-Dr. Umar's UGraft: find out why it is superior.
-Dr. Bisanga 2924 grafts FUE, 8 months.
-Dr. Arvind presentations at ISHRS & AAHRS conference.
-Dr. Baubac (Alvi Armani): 3995 grafts FUE for NW4.

-Dr. Jones: 6000 grafts FUE megasession, 4 months.

roger_that

MARYLAND,
15.10.2012, 19:27
(edited by roger_that, 15.10.2012, 20:04)
 

PGD2 linked to DHT - and how to reverse hair loss (Hair Multiplication & Stem Cells Treatment)

First of all I want to post this:

http://www.genecards.org/cgi-bin/carddisp.pl?gene=PTGDS

Which is a link to a "gene card", sort of like a baseball card for human genes, which shows all the relevant info and stats on the enzyme PGD2 Synthase. This is the one and only enzyme in the human body which synthesizes the prostaglandin called PGD2.

PGD2 Synthase exists in many places in the human body, but this gene card is entitled "prostaglandin D2 synthase 21kDa (brain)" because much of the experimental information, measurements, etc. shown here refer to PGD2 Synthase extracted from the human brain, where the enzyme is plentiful. (This should not lead people to believe that all PGD2 is systhesized in the brain, or that most of it is... or that the PGD2 in your scalp came from the brain. WRONG! Nothing could be further from the truth, although I have read several articles on the internet, in allegedly "reputable" Web publications, which stated or implied that. Also, I've seen authors confusing PGD2 Synthase with PGD2, and calling PGD2 an "enzyme". Also WRONG! It shows you what passes for internet-based science journalism these days... they are hiring their so-called "science writers" on the cheap!)

People should not confuse PGD2 with PGD2 Synthase.

PGD2 is a prostaglandin.

PGD2 Synthase is an enzyme which makes PGD2.

PGD2 Synthase, being an enzyme, is also a protein.

PGD2 is a small molecule with a very short half-life, and always acts very locally (i.e., in very close proximity to the place where it was synthesized). It never travels a long distance through your bloodstream -- the molecule wouldn't survive the trip.

PGD2 Synthase is a much bigger molecule and its sole job is to synthesize PGD2 (the prostaglandin) by taking another prostaglandin, PGH2, and changing its molecular structure a little bit.


The word "Synthase" just means "an enzyme that creates"... as in creating PGD2 by converting PGH2 into PGD2.

If you look at the section on the PGD2 Synthase gene card titled "Tissue Specificity" (way down on the page), you'll see that the enzyme (and therefore PGD2 itself) can be found in a number of bodily tissues, including: the brain, the heart, the male reproductive system, the prostate gland, the eye, etc. It does not mention the scalp of people with MPB, which tells me that this data was either collected before Dr. Cotsarelis' study was published, or afterwards and they just didn't think it necessary to update, because they thought that point was relatively trivial.

Moving upwards on the page, about a third of the way down the page, under "Function Summary", you'll see that various biochemical triggers in the body can "induce" the synthesis of PGD2 Synthase (here they're talking about the synthesis of the synthase enzyme, not the enzyme's synthesis of PGD2). Those substances include the following:

dexamethasone, dihydrotestosterone (DHT), progesterone, retinoic acid and retinal.

SO, there you have it, my peeps: PGD2 Synthase, the one and only enzyme in the human body responsible for the production of that hair poison known as PGD2, can be induced by none other than our main man, DHT!

Now, before anyone accuses me of stating or restating the obvious, I'll say that (1) this is the first time I've seen this particular connection noted on this board and (2) I'm sure Dr. Cotsarelis is aware of this connection, in fact, I'm guessing this connection has been known for a while and isn't something that just surfaced when he did his PGD2 study. (In fact, it is entirely possible that this known connection was one thing that encouraged him to take a special look at PGD2, since all you have to do is run a search of all these gene cards using "DHT" as a search term, and one molecule you'll find that DHT can induce is PGD2 Synthase.)

In any event, since we know that DHT can induce (which roughly translates as "indirectly generate" -- as in to generate by some roundabout or multi-step pathway) PGD2 Synthase, and, by extension, PGD2 itself, it makes sense that Dr. Cots found a connection between PGD2 and MPB.

Now, all this got me thinking. I was thinking this morning about why, when people with MPB are treated with various DHT blockers, DHT inhibitors, and DHT antagonists, or anti-androgens, like Finasteride or Dutasteride, etc., they may regrow a little hair, but generally all it does is stop further hair loss.

Does that mean that once hair is lost, it can only be regrown to a tiny extent, but the vast majority of the hair lost can never be brought back because of some problem like "the follicles are dead"?

And when prisoners are castrated or men were turned into eunuchs, if they were balding, the balding process would stop but in general they wouldn't regrow much hair.

That would also indicate that balding is (with a few marginal and only partial exceptions) a one-way, unidirectional proposition -- you will lose your hair, but those same follicles can never be revived.

Right?

Then I started thinking about how DHT and PGD2 might be different.

Well, we know that DHT is basically a steroid hormone. It's a derivative of Testosterone, and like T and all other steroid hormones, it enters the nucleus of the cell and interacts with the DNA, changing it in some way -- usually by switching on or switching off some gene. And remember, this happens in millions of cells, in great waves of change that pass over the tissues as the they are perfused with testosterone or DHT. EVERYTHING in cell biology, biochemistry, and genetics is a mass process -- we're ALWAYS talking a statistical game of billions of reactions in hundreds of millions of cells over a period of time.

Then I thought, we know DHT and PGD2 are linked, and that it's very likely that DHT somehow induces the offending PGD2 Synthase, and by extension, the nefarious PGD2, in balding people's scalps.

How do those two molecules differ?

Well, for one, PGD2 is NOT a steroid hormone, and it does NOT enter the cell nucleus. It does not (generally, and possibly ever) interact directly with the DNA. Its actions are local and happen most likely in or near the intra-cellular spaces.

But why would Dutasteride only stop further hair loss and not bring back much hair in most people?

Why would castrated men who are balding only have their hair loss stop, and not regrow hair?

Is it that most of the time the follicles die?

Or is there another explanation?

What if DHT was turning on a genetic switch within hair follicle cells which instructed the cells to create a lot of PGD2 Synthase (and therefore a lot of PGD2)... but what if once the DHT is blocked or removed, those genes stay switched on?

This is an entirely possible scenario and happens all the time in genetics. There are many examples of one-way switches in human genetics whereby a particular molecule can switch on a gene, but when the gene gets switched on, it gets switched on indefinitely, even if you remove the initial molecule which triggered that state.

That would explain why just blocking or inhibiting DHT or androgens in general isn't enough.

If this were the case, then once your follicle cells are exposed to enough DHT, enough of their genes for PGD2 Synthase get turned on... and they never get turned off.

That would mean that even if you block all the incoming DHT or androgens, you still have all these millions of tiny factories in your follicles cranking out the PGD2 and keeping the follicles into a coma... from which they never awaken.

Even if you block, arrest, inhibit, suppress, or destroy the DHT, it will never be enough to bring back all your hair.

And since PGD2 is a prostaglandin it works in a very narrowly-targeted, pinpoint location, so that the cells with the switched-on genes continue to propagage PDG2, and the cells with the genes that were never switched on (after you take away the DHT), don't start propagating PGD2. Stopping your hair loss dead in its tracks with the same pattern that doesn't change, as long as you don't stop blocking the DHT.

But now the good part.... the corollary of that is that you can still block the PGD2 -- or its receptor, GPR44 -- and that might actually give you a chance to get your hair back.

In other words, targeting PGD2 which is synthesized downstream of DHT might actually work, not just to stop the MPB process, but also to reverse its effects!

Then you can throw in some Dutasteride, too (as AlecBaldone suggested he was going to do recently), for good measure -- to make sure that no ADDITIONAL PGD2 Synthase is induced.

I really think that it is entirely possible be the first EVER treatment that has the potential not just to stop baldness in its tracks, but to SUBSTANTIALLY reverse it.

Would be interested to see what people here think.

Would be interested to see what Dr. Cotsarelis might think.




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
jarjarbinx

15.10.2012, 21:17
(edited by jarjarbinx, 15.10.2012, 21:53)

@ roger_that

PGD2 linked to DHT - and how to reverse hair loss

1. If DHT can cause the production of PGD2 then it's possible that other androgens, such as testosterone, can also do the same thing. How exactly does DHT produce PGD2? If DHT produces PGD2 as a byproduct of synthesis after the DHT binds to an androgen receptor then now would be a good time to point out that testosterone is also an androgen and it also binds to that same receptor and does the same synthesis with the only exception being that testosterone's synthesis is less potent.


DHT synthesis = Androgen binds to androgen receptor resulting in androgen synthesis.

TESTOSTERONE synthesis = Androgen binds to androgen receptor resulting in androgen synthesis.


2. Androgens other than DHT play a role in hair loss. I know this because I got much better results from topical RU58841 than I did from oral or topical finasteride.

3. The reason why castration does not cause more substantial hair growth is because even after castration the body still produces androgens in the andrenal glands. Castration will arrest hair loss but in order to reverse hair loss substantially you have negate more androgen than you negate via castration.




jarjarbinx is located in [NA] and he is available to meet: NO


Post reply
roger_that

MARYLAND,
15.10.2012, 21:27

@ jarjarbinx

PGD2 linked to DHT - and how to reverse hair loss

1. If DHT can cause the production of PGD2 then it's possible that other
androgens, such as testosterone, also can.

Definitely possible. But the gene card profile doesn't say anything about other androgens doing it. I would think that if it were known they do, that information would be on the gene card by now.

2. Androgens other than DHT play a role in hair loss. I know this because I
got much better results from RU58841 than I did from finasteride.

Definitely, but DHT is the strongest in that regard. However, if other androgens play a role (I believe they do) and even if they specifically induce PGD2, that still doesn't change my analysis. It's just one more way that analysis can be true.

3. The reason why castration does not cause more substantial hair growth is
because even after castration the body still produces androgens in the
andrenal glands.

Yes, that is very true. Good point, and I know that. I believe the adrenal glands produce about 1/10th the amount of androgens as the testicles do, but it's still significant.

Prior to Dr. Cots' findings, we knew DHT was intimately involved in causing MPB, we just didn't know the "how". I believe we now know the "how".

I believe the DHT-mediated genetic switch for PGDG2 Synthase induction will turn out to be a "one-way" switch meaning once it's turned on, a lot of PGD2 Synthase is created by the DNA in that area and by and large, it can never be switched off except by directly changing the DNA back to its prior state.

Since that is damn near impossible (not completely impossible, but damn near), the best way to reverse MPB is to attack it downstream of that "irreversible" genetic switch, by neutralizing or inhibiting whatever products it's creating.




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
jarjarbinx

15.10.2012, 21:43

@ roger_that

DHT and Testosterone

You might be right. We may have a cure. This is the most hope I've had in a long time. The main thing to me Roger is that now that you have shown that DHT definitely produces DHT it seems to me that the next big question is how does DHT produce PGD2?

You see, I do not believe that DHT could produce PGD2 simply by its' existence in the body. If DHT produces PGD2 by way of DHT's synthesis after DHT binds to the androgen receptor then I think that means that there's a possibility that testosterone does the same thing. You see when push comes to shove DHT and testosterone are very similar and they act in similar ways.

1. They're both androgens.

2. They both bind to androgen receptors.

3. They both produce an androgen synthesis after binding to the androgen receptors.


It just seems to me that since they are both very similar in the first place, both bind to the same receptor, and both do essentially the same synthesis after binding to that same receptor, they may both produce a very similar downstream result after synthesis.








1. If DHT can cause the production of PGD2 then it's possible that other
androgens, such as testosterone, also can.

Definitely possible. But the gene card profile doesn't say anything about
other androgens doing it. I would think that if it were known they do,
that information would be on the gene card by now.

2. Androgens other than DHT play a role in hair loss. I know this because
I
got much better results from RU58841 than I did from finasteride.

Definitely, but DHT is the strongest in that regard. However, if other
androgens play a role (I believe they do) and even if they specifically
induce PGD2, that still doesn't change my analysis. It's just one more
way that analysis can be true.

3. The reason why castration does not cause more substantial hair growth
is
because even after castration the body still produces androgens in the
andrenal glands.

Yes, that is very true. Good point, and I know that. I believe the
adrenal glands produce about 1/10th the amount of androgens as the
testicles do, but it's still significant.

Prior to Dr. Cots' findings, we knew DHT was intimately involved in causing
MPB, we just didn't know the "how". I believe we now know the "how".

I believe the DHT-mediated genetic switch for PGDG2 Synthase induction will
turn out to be a "one-way" switch meaning once it's turned on, a lot of
PGD2 Synthase is created by the DNA in that area and by and large, it can
never be switched off except by directly changing the DNA back to its prior
state.

Since that is damn near impossible (not completely impossible, but damn
near), the best way to reverse MPB is to attack it downstream of that
genetic "irreversible" switch, by neutralizing or inhibiting whatever
products it's creating.




jarjarbinx is located in [NA] and he is available to meet: NO


Post reply
jarjarbinx

15.10.2012, 21:50
(edited by jarjarbinx, 15.10.2012, 22:06)

@ roger_that

PGD2 linked to DHT - and how to reverse hair loss

All of this does kind of make me wonder if negating PGD2 and the other postaglandins that take our hair might also feminize the male body and cause impotence and loss of vigor. I sure hope not. Hopefully, androgen synthesis results in more than one stream of events. Hopefully the post-androgen synthesis (after androgen receptor binding) stream of events that produces hair loss is not the same stream of events that produces male virility and the male physique.



1. If DHT can cause the production of PGD2 then it's possible that other
androgens, such as testosterone, also can.

Definitely possible. But the gene card profile doesn't say anything about
other androgens doing it. I would think that if it were known they do,
that information would be on the gene card by now.

2. Androgens other than DHT play a role in hair loss. I know this because
I
got much better results from RU58841 than I did from finasteride.

Definitely, but DHT is the strongest in that regard. However, if other
androgens play a role (I believe they do) and even if they specifically
induce PGD2, that still doesn't change my analysis. It's just one more
way that analysis can be true.

3. The reason why castration does not cause more substantial hair growth
is
because even after castration the body still produces androgens in the
andrenal glands.

Yes, that is very true. Good point, and I know that. I believe the
adrenal glands produce about 1/10th the amount of androgens as the
testicles do, but it's still significant.

Prior to Dr. Cots' findings, we knew DHT was intimately involved in causing
MPB, we just didn't know the "how". I believe we now know the "how".

I believe the DHT-mediated genetic switch for PGDG2 Synthase induction will
turn out to be a "one-way" switch meaning once it's turned on, a lot of
PGD2 Synthase is created by the DNA in that area and by and large, it can
never be switched off except by directly changing the DNA back to its prior
state.

Since that is damn near impossible (not completely impossible, but damn
near), the best way to reverse MPB is to attack it downstream of that
"irreversible" genetic switch, by neutralizing or inhibiting whatever
products it's creating.




jarjarbinx is located in [NA] and he is available to meet: NO


Post reply
Ahab

15.10.2012, 21:58

@ roger_that

PGD2 linked to DHT - and how to reverse hair loss

Someone should test the scalps of balding people before and after taking Avodart and/or Finasteride, to see if there is less PGD2 in their scalps after taking Avodart or Finasteride.




Ahab is located in [NA] and he is available to meet: NO


Post reply
roger_that

MARYLAND,
15.10.2012, 22:03

@ jarjarbinx

DHT and Testosterone

You might be right. We may have a cure. This is the most hope I've had in
a long time. The main thing to me Roger is that now that you have shown
that DHT definitely produces DHT it seems to me that the next big question
is how does DHT produce PGD2?

You see, I do not believe that DHT could produce PGD2 simply by its'
existence in the body. If DHT produces PGD2 by way of DHT's synthesis
after DHT binds to the androgen receptor then I think that means that
there's a possibility that testosterone does the same thing. You see when
push comes to shove DHT and testosterone are very similar and they act in
similar ways.

1. They're both androgens.

2. They both bind to androgen receptors.

3. They both produce an androgen synthesis after binding to the androgen
receptors.


I think you're mixing apples and oranges a bit here.

Both DHT and other testosterone bind to androgen receptors, but there are different kinds of androgen receptors.

DHT preferentially binds to the DHT receptor which is one specific type of androgen receptor. Doesn't mean it doesn't bind to other androgen receptors, it just preferentially binds to DHT receptors. Furthermore the preference is a strong one, not a weak one. In other words, if both receptors are present, all other things being equal, it will definitely bind to the DHT receptor not another kind of androgen receptor.

Same is true for every other different kind of androgen.

Furthermore there is probably a range of sub-types of DHT receptors which are slightly different and do different things in different parts of the body. While DHT always has the exact same molecular structure, different DHT receptors in different parts of the body might be slightly different.

I think you're making way too much of the similarities between DHT and testosterone, and conflating all that.

There is ample scientific evidence that implicates DHT as being by far the most important androgen in causing MPB. All the other androgens, while they might technically play a role, play peripheral roles.

For instance, personally I believe that it is the cumulative effects of testosterone that accounts for geriatric alopecia in elderly men -- a general thinning of the scalp hair. This happens at a much slower rate than MPB. And even though elderly men have much less testosterone than younger men, the effect is cumulative and like the PGD2 effect, it is essentially irreversible (indeed, as you have hinted by equating the effects of DHT and testosterone, it too might be mediated through PGD2.)

My point here is that although I completely recognize the roles that other androgens play in MPB and some other types of alopecia, I believe you are conflating DHT with testosterone and over-exaggerating their similarities, just because of your interpretation of something anecdotal that happened to YOU.

Be aware that whatever your experience was with RU, you have put your own interpretation on why it happened, and that might not be the correct interpretation... or there may be other explanations which are equally good.




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
Ahab

15.10.2012, 22:05

@ roger_that

PGD2 linked to DHT - and how to reverse hair loss

Instead of this one way switch idea, it could also be--as I've said before--that hair follicles are programmed to go through the hair cycle a set number of times, and that exposure to DHT shortens the time between cycles so that the cycles get used up at a younger age, making such men bald.

This would also explain why using DHT blockers on bald or already balding men does not cure hair loss; because although blocking DHT may lengthen the time between cycles, there are too few cycles left, so the person loses his hair anyway.

And that would be why the earlier someone takes DHT blockers, the longer they will continue to grow hair.

And why someone who is already slick bald when starting DHT blockers, gets no meaningful results.




Ahab is located in [NA] and he is available to meet: NO


Post reply
roger_that

MARYLAND,
15.10.2012, 22:08

@ Ahab

PGD2 linked to DHT - and how to reverse hair loss

Someone should test the scalps of balding people before and after taking
Avodart and/or Finasteride, to see if there is less PGD2 in their scalps
after taking Avodart or Finasteride.

Good idea, and my guess is that there probably wouldn't be much less PGD2. The difference would be either non-existent or relatively nominal.




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
Freddie555

15.10.2012, 22:11

@ roger_that

PGD2 linked to DHT - and how to reverse hair loss

if its being synthesized in the brain, we are fuc,ked.

we'd have to blow our brains out to get rid of it.




Freddie555 is located in [NA] and he is available to meet: NO

---
"When true Hair Multiplication comes, it will arise out of the East." - John The Revelator, Feb. 18, 2001


Post reply
roger_that

MARYLAND,
15.10.2012, 22:12

@ Ahab

PGD2 linked to DHT - and how to reverse hair loss

Instead of this one way switch idea, it could also be--as I've said
before--that hair follicles are programmed to go through the hair cycle a
set number of times, and that exposure to DHT shortens the time between
cycles so that the cycles get used up at a younger age, making such men
bald.

I don't disagree with you there, I just think it's more like DHT puts the follicles into a coma, with extreeeeeemely elongated telogen phases and extremely shortned anagen phases until ultimately the anagen phase is like nothing.

And I think that this is all mediated by a one-way genetic switch wherein PGD2 Synthase synthesis is turned on in the DNA.

So it's basically something like a combination of your idea and my idea, but we are both looking at different points in the process.

You are talking about what DHT does, and I'm saying that there are several other essential steps in-between "what DHT does" and follicle miniaturization, namely, "what PGD2 Synthase and PGD2 do".




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
roger_that

MARYLAND,
15.10.2012, 22:16

@ jarjarbinx

PGD2 linked to DHT - and how to reverse hair loss

All of this does kind of make me wonder if negating PGD2 and the other
postaglandins that take our hair might also feminize the male body and
cause impotence and loss of vigor.

No more danger of that than the danger posed by rubbing an anti-androgen into your scalp. A PGD2 blocker would most likely be topical.




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
ipod

15.10.2012, 23:26

@ roger_that

PGD2 linked to DHT - and how to reverse hair loss

this reminds me of finasteride and dht, finasteride doesn't suppress dht directly, instead if inhibits the enzyme 5-alpha reductase (5AR) because 5AR is the enzyme that converts testosterone to dht. now we also have enzyme that is responsible for the production of PGD2, targeting the enzyme maybe a more proactive way to deal with PGD2, without the enzyme we won't even have to worry about the existence of PGD2 at all.




ipod is located in [NA] and he is available to meet: NO


Post reply
jarjarbinx

16.10.2012, 00:30

@ ipod

PGD2 linked to DHT - and how to reverse hair loss

this reminds me of finasteride and dht, finasteride doesn't suppress dht
directly, instead if inhibits the enzyme 5-alpha reductase (5AR) because
5AR is the enzyme that converts testosterone to dht. now we also have
enzyme that is responsible for the production of PGD2, targeting the enzyme
maybe a more proactive way to deal with PGD2, without the enzyme we won't
even have to worry about the existence of PGD2 at all.

WTF?

Go ahead and waste a decade or so your time if you want to. About 7 to 10 years from now an inhibitor of the enzyme that is responsible for the production of PGD2 may get to the same point where the GPR44-blockers are already at right now but since the GPR44 blockers are already very close to coming to market it would be more expeditious to go the GPR44-blocker route instead. Don't ya think?

I think I would rather use a GPR44-blocker very soon rather than wait 7 - 10 years for companies to bring a drug like you are talking about to market.

Don't ya think?




jarjarbinx is located in [NA] and he is available to meet: NO


Post reply
Bryan

16.10.2012, 00:49

@ roger_that

DHT and Testosterone

DHT preferentially binds to the DHT receptor which is one specific
type of androgen receptor. Doesn't mean it doesn't bind to other androgen
receptors, it just preferentially binds to DHT receptors.

What makes you think there's a specific "DHT receptor"?




Bryan is located in [NA] and he is available to meet: NO


Post reply
cal

16.10.2012, 01:02

@ Bryan

DHT and Testosterone

Ahab -

I recall it being observed that MPB can measurably miniaturize a hair shaft over the course of a single hair cycle in some cases. That would seem to invalidate your theory about MPB being the result of the lifetime supply of hair cycles being used up too early.


But I still think you might be onto something with the theory that follicles have a finite number of hair cycles per human lifetime.




cal is located in [NA] and he is available to meet: NO


Post reply
roger_that

MARYLAND,
16.10.2012, 07:24
(edited by roger_that, 16.10.2012, 08:02)

@ Bryan

DHT and Testosterone

What makes you think there's a specific "DHT receptor"?

Articles like this:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1048919/

http://www.nature.com/pr/journal/v15/n1/full/pr198190a.html




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
Bryan

16.10.2012, 14:39

@ roger_that

DHT and Testosterone

What makes you think there's a specific "DHT receptor"?

Articles like this:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1048919/

http://www.nature.com/pr/journal/v15/n1/full/pr198190a.html

I don't think a couple of 30-year-old studies are valid any longer. Before I posted my question above, I deliberated mentioning myself that I had also seen a couple of such studies that mentioned such a reference to "DHT receptors", but not in recent years. I think everybody knows now (including doctors and researchers) that androgen receptors work with ALL androgens, including DHT.




Bryan is located in [NA] and he is available to meet: NO


Post reply
roger_that

MARYLAND,
16.10.2012, 18:17

@ Bryan

DHT and Testosterone

I don't think a couple of 30-year-old studies are valid any longer. Before
I posted my question above, I deliberated mentioning myself that I had also
seen a couple of such studies that mentioned such a reference to "DHT
receptors", but not in recent years. I think everybody knows now
(including doctors and researchers) that androgen receptors work with ALL
androgens, including DHT.

I'm not disputing that androgen receptors can work with all androgens. If you re-read my post, I indicated that the same receptor could bind either testosterone or DHT, or even other androgens. Maybe I'm partly misinformed in that I implied that the receptors were physically different. Another way of looking at the same thing, though, is that when an androgen receptor binds testosterone, it's a testosterone receptor by default and when it binds DHT, it's a DHT receptor by default.

In any event, what is this, a chess game where we have to deliberate our comments cautiously before we post?

The point of my post wasn't about parsing the molecular structures of androgen receptors for minor differences. It was about my hypothesis that there's a one-way genetic switch involving PGD2 Synthase, activated or induced by DHT. THAT was clearly the central point of my post.

Would you care to offer an opinion on my central point?




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
jarjarbinx

16.10.2012, 18:57

@ Bryan

DHT and Testosterone

What makes you think there's a specific "DHT receptor"?

Articles like this:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1048919/

http://www.nature.com/pr/journal/v15/n1/full/pr198190a.html

I don't think a couple of 30-year-old studies are valid any longer. Before
I posted my question above, I deliberated mentioning myself that I had also
seen a couple of such studies that mentioned such a reference to "DHT
receptors", but not in recent years. I think everybody knows now
(including doctors and researchers) that androgen receptors work with ALL
androgens, including DHT.

So then you agree with my point that these androgens (DHT and testosterone) are binding to the same receptor. I read the T. Battman study involving RU58841 and I spoke with T. Battman on the telephone myself and both in the study and on the telephone Mr. Battman talks about the "androgen receptor" as if to indicate that we are talking about a single receptor for all androgens.




jarjarbinx is located in [NA] and he is available to meet: NO


Post reply
jarjarbinx

16.10.2012, 19:11
(edited by jarjarbinx, 16.10.2012, 19:28)

@ roger_that

DHT and Testosterone

I don't think a couple of 30-year-old studies are valid any longer.
Before
I posted my question above, I deliberated mentioning myself that I had
also
seen a couple of such studies that mentioned such a reference to "DHT
receptors", but not in recent years. I think everybody knows now
(including doctors and researchers) that androgen receptors work with
ALL
androgens, including DHT.

I'm not disputing that androgen receptors can work with all androgens. If
you re-read my post, I indicated that the same receptor could bind either
testosterone or DHT, or even other androgens. Maybe I'm partly misinformed
in that I implied that the receptors were physically different. Another way
of looking at the same thing, though, is that when an androgen receptor
binds testosterone, it's a testosterone receptor by default and when it
binds DHT, it's a DHT receptor by default.

In any event, what is this, a chess game where we have to deliberate our
comments cautiously before we post?

The point of my post wasn't about parsing the molecular structures of
androgen receptors for minor differences. It was about my hypothesis that
there's a one-way genetic switch involving PGD2 Synthase, activated or
induced by DHT. THAT was clearly the central point of my post.

Would you care to offer an opinion on my central point?


Roger_that please post links proving your claim that there are multiple androgen receptors and that each different androgen predominantly binds to its' specific receptor rather than there being one androgen receptor with all androgens binding to that same receptor.

I remember seeing a study wherein researchers increased testosterone levels in the skin in an attempt to reduce DHT binding to the androgen receptor. DHT has a higher affinity to the androgen receptor than testsosterone so more DHT than testosterone binds to the receptor. DHT and testosterone compete for binding at the same receptor. Researchers decided to increase the amount of testosterone to see if increased testosterone would lead to more testosterone binding to the receptor, and less DHT binding to the receptor. These researchers clearly were operating under the premise that DHT and testosterone bind to the same receptor.

One androgen receptor:

http://www.ncbi.nlm.nih.gov/pubmed/6891012

All androgens act through the same receptor:

http://www.endotext.org/male/male3/index.html


Please provide links that show otherwise since that is your claim.




jarjarbinx is located in [NA] and he is available to meet: NO


Post reply
roger_that

MARYLAND,
16.10.2012, 20:10

@ jarjarbinx

This issue is a distraction

Here's something I found. This is from 2008, so maybe it's already ancient history, and may not be exactly on point to what Bryan is talking about, but here it is anyway:

http://www.molecular-cancer.com/content/7/1/88

"An increasing body of scientific evidence points to the existence of two types of androgen receptors: (a) intracellular androgen receptors (iARs) mediating genomic androgen signals resulting in receptor dimerization, nuclear translocation and subsequent activation of androgen-specific target genes (reviewed in [1]) and (b) membrane androgen receptors (mARs) triggering non-genomic signals manifested within minutes of androgen binding (reviewed in [2,3])."

Anyway, this issue about different types of androgen receptors, be they DHT, testosterone, intracellular iARs, membrane mARs, or whatever is a total distraction and SIDE ISSUE, not relevant to my main point in the original post on this thread... Which is my hypothesis about a one-way genetic switch for the PGD2 Synthase gene, activated or induced by DHT.

It's funny how people here can read my post, and then latch onto not the central theme in my post, but a relatively insignificant side-issue which really doesn't affect the plausibility of the hypothesis one way or another.

Whether there is one kind of androgen receptor, or two, or a thousand, doesn't affect the fact that the information on the PGD2 Synthase gene card says that PGD2 Synthase is induced by DHT (not testosterone, I remind you)...

Does it? I leave that question for the brilliant eminences here on this forum to debate.




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
jarjarbinx

16.10.2012, 20:35

@ roger_that

It's not a distraction. It's a key point.

In an attempt to prove it's very possible that testosterone produces PGD2 I asserted that since DHT produces PGD2 that means that testosterone may also produce PGD2. This point is NOT a distraction. This is a major important point because you are asking why the elimination of DHT (by way of 5 alpha reductase inhibitors) only arrests hair loss but does not regrow a lot of hair. I'm pointing out that by eliminating DHT that only eliminates some of the PGD2 (the PGD2 created by DHT) but may not eliminate all of the PGD2 because there may still be the PGD2 that is created by testosterone. This is a major point. It answers a question that you asked. And now that we have examined your claim that each androgen has its' own receptor I think that it is largely proved that your claim is incorrect and this supports my claim that the similarities between DHT and testosterone are very similar.

1. testosterone and DHT are both powerful androgens.

2. both testosterone and DHT bind to the same recptor.

These two hormones are very similar hormones in what they essentially are, and in that they both bind to the same receptor, and in that when they bind to that receptor it results in the same androgen synthesis, although the androgen synthesis they each produce has a different strength. It does seem to me that if the synthesis of one produces PGD2 then the other might as well.




jarjarbinx is located in [NA] and he is available to meet: NO


Post reply
jarjarbinx

16.10.2012, 20:49

@ roger_that

PGD2 linked to DHT - and how to reverse hair loss


Moving upwards on the page, about a third of the way down the page, under
"Function Summary", you'll see that various biochemical triggers in the
body can "induce" the synthesis of PGD2 Synthase (here they're talking
about the synthesis of the synthase enzyme, not the enzyme's synthesis of
PGD2). Those substances include the following:

dexamethasone, dihydrotestosterone (DHT), progesterone, retinoic
acid and retinal.

SO, there you have it, my peeps: PGD2 Synthase, the one and only enzyme
in the human body responsible for the production of that hair poison known
as PGD2, can be induced by none other than our main man, DHT!




It does seem to me that this shows that things besides androgens produce this PGD2 Synthase stuff. Roger_that, I think this is an interesting point. DHT is an androgen, but what are these other things:

1. dexamethasone

2. progesterone

3. retinoic acid

4. retinal

What are these things Roger_that? These things are part of the problem too aren't they? If they are then it might be a good idea to try to understand them, what they are, and what increases or decreases the supply of this stuff in the body. One of them is retinoic acid and it's my understanding that people use retinoic acid mixed in with their rogaine to make the rogaine stronger.


Are any of these other 4 things androgen(s):

1. dexamethasone

2. progesterone

3. retinoic acid

4. retinal




jarjarbinx is located in [NA] and he is available to meet: NO


Post reply
Bryan

17.10.2012, 02:51

@ jarjarbinx

DHT and Testosterone

So then you agree with my point that these androgens (DHT and testosterone)
are binding to the same receptor. I read the T. Battman study involving
RU58841 and I spoke with T. Battman on the telephone myself and both in the
study and on the telephone Mr. Battman talks about the "androgen receptor"
as if to indicate that we are talking about a single receptor for all
androgens.

Yes, I totally agree with you, and with Dr. Battman. I thought it was downright peculiar to see someone referring to "DHT receptors", as if I fell into a time-warp and went back 30 or 40 years ago! :)




Bryan is located in [NA] and he is available to meet: NO


Post reply
Bryan

17.10.2012, 03:00

@ roger_that

DHT and Testosterone

I'm not disputing that androgen receptors can work with all androgens. If
you re-read my post, I indicated that the same receptor could bind either
testosterone or DHT, or even other androgens. Maybe I'm partly misinformed
in that I implied that the receptors were physically different.

I think you were misinformed to believe that they're physically different.

Another way
of looking at the same thing, though, is that when an androgen receptor
binds testosterone, it's a testosterone receptor by default and when it
binds DHT, it's a DHT receptor by default.

I have no idea what that means.




Bryan is located in [NA] and he is available to meet: NO


Post reply
roger_that

MARYLAND,
17.10.2012, 07:02
(edited by roger_that, 17.10.2012, 07:38)

@ Bryan

DHT and Testosterone

I think you were misinformed to believe that they're physically different.

OK, if the receptors are not physically different, I stand corrected. I'm not trying to present myself as an expert on every aspect of the biochemical basis of hairloss. I am a humble non-scientist on this forum, a dilettante just offering ideas.

Please don't let it distract you from the main issue in my post, though -- which is my hypothesis about the one-way genetic switch for the PGD2 Synthase gene, induced by DHT. Can you please offer us an opinion on that?




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
roger_that

MARYLAND,
17.10.2012, 07:11

@ Bryan

DHT and Testosterone

Yes, I totally agree with you, and with Dr. Battman. I thought it was
downright peculiar to see someone referring to "DHT receptors", as
if I fell into a time-warp and went back 30 or 40 years ago! :)

I admitted I was wrong and I'm sorry about that. Is your point to politely correct my mistake, or to ridicule me?




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
roger_that

MARYLAND,
17.10.2012, 18:53

@ jarjarbinx

It's not a distraction. It's a key point.

OK, jarjar, I understand your point and I see what you're saying. Testosterone (and maybe other androgen variations) also play a role in MPB; they all act through that androgen receptor, so they must also have some role in generating PGD2. I'm sure you're correct about that, but that doesn't change the fact that DHT is singled out as being the most important androgen in MPB. Not to mention that of all the possible androgens, DHT was the one and only androgen connected with induction of PGD2 Synthase on that gene card.

The other thing is you have to remember that it's all relative. Let's say, for example (I'm just throwing out hypothetical numbers here, these are NOT based on knowledge of any facts), that DHT is 70% responsible for MPB, and testosterone's and all the other minor androgens' joint contribution to MPB can be quantified at 30%.

Now let's assume your theory (at least something you've stated or implied here from time to time), that to get full regrowth of hair, you have to block EVERY androgen, not just DHT.

Then, according to that theory, and given those hypothetical figures above, if you block DHT with a DHT blocker, you should get 70% regrowth. But since the other androgens are not being blocked, after the treatment has time to work, you would still remain 25% bald.

But we know that is not the case. In the vast majority of people who use a DHT-specific anti-androgen, they don't regrow a large portion of their hair like that.

Let's assume, then, that DHT accounts for only 50% of the effect, with testostserone and all the other androgens put together accounting for the other 50%.

Then, if I use a DHT blocker and it really blocks all (or almost all) of the DHT, but I don't do anything to block all the other androgens, I should regrow 50% of my hair... at least according to the theories or ideas you have sometimes put forward here.

But we know that doesn't happen, either.

We can't say that DHT is only responsible for less than a 50% contribution to MPB, because that would mean it's no longer the "major" cause of MPB, right?

But we know that even when people have ALL, or almost all, androgens blocked, the vast majority don't regrow all their hair or anything close to it. (I realize you said you did when you used RU, and I'm not discounting that or doubting it... it may be true and you're just a fluke, and there is probably a really valid biochemical reason for what happened to you... and it probably does have to do with blocking all the androgens... but what I am saying is that if this were found to be possible in a sizable number of people, lots of people would already be doing it and it would be considered a de facto cure for MPB.)

What I'm saying is that the real way to reverse hair loss is probably downstream of all that androgen stuff. It doesn't mean androgens aren't responsible. Androgens are very definitely responsible; you wouldn't get bald if it weren't for androgens.

What I'm saying is that in the vast, vast majority of cases, you can't reverse MPB to any reasonable extent by just blocking androgens (whether it's DHT, testosterone, or any combination of androgens... including all of them.) You have to block something else.

That's why I think there's a biochemical choke point involved here and I think that it's a one-way genetic switch at the PGD2 Synthase gene. It is most likely stimulated by DHT and/or other androgens, like testosterone (most strongly by DHT, though.) When this switch is activated, it causes PGD2 Synthase crank out ridiculous amounts of PGD2, which basically puts people's follicles into a coma by gradually shortening the anagen phase and dragging out the telogen phase.

Removing or blocking one, two, or all the androgens is generally enough to stop further hair loss but, in almost all cases, it is NOT ENOUGH to actually reverse the follicle miniaturization process to any significant degree. The only way to reverse that biochemically is by blocking or negating the PGD2 somehow, or by blocking or inactivating the enzyme.




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
jarjarbinx

17.10.2012, 20:27

@ roger_that

It's not a distraction. It's a key point.

Based on my experience with 5-alpha reductase inhibitors and anti-androgens I would say that it does not work the way you are thinking. I would say that there are 3 different biological tasks and each has a different threshold you have to reach in order to accomplish the task at hand.

1. Preventing hair loss before hair loss starts. I would say this requires the least amount of androgen suppression.

2. Arresting hair loss after hair loss has already started. This takes more androgen suppression than preventing hair loss before hair loss starts but less androgen suppression than reversing hair loss after hair loss starts.

3. Arresting hair loss plus reversing hair loss after hair loss starts. This biological task requires the most androgen suppression and if you don't reach a minimum amount of androgen suppression then you can not succeed at this task. You have to negate nearly ALL androgen in the target tissue in order to achieve this task. Anything less and you won't succeed at this task.



OK, jarjar, I understand your point and I see what you're saying.
Testosterone (and maybe other androgen variations) also play a role in MPB;
they all act through that androgen receptor, so they must also have some
role in generating PGD2. I'm sure you're correct about that, but that
doesn't change the fact that DHT is singled out as being the most important
androgen in MPB. Not to mention that of all the possible androgens, DHT
was the one and only androgen connected with induction of PGD2 Synthase on
that gene card.

The other thing is you have to remember that it's all relative. Let's
say, for example (I'm just throwing out hypothetical numbers here, these
are NOT based on knowledge of any facts), that DHT is 70%
responsible for MPB, and testosterone's and all the other minor androgens'
joint contribution to MPB can be quantified at 30%.

Now let's assume your theory (at least something you've stated or implied
here from time to time), that to get full regrowth of hair, you have to
block EVERY androgen, not just DHT.

Then, according to that theory, and given those hypothetical figures above,
if you block DHT with a DHT blocker, you should get 70% regrowth. But
since the other androgens are not being blocked, after the treatment has
time to work, you would still remain 25% bald.

But we know that is not the case. In the vast majority of people who use a
DHT-specific anti-androgen, they don't regrow a large portion of their hair
like that.

Let's assume, then, that DHT accounts for only 50% of the effect, with
testostserone and all the other androgens put together accounting for the
other 50%.

Then, if I use a DHT blocker and it really blocks all (or almost all) of
the DHT, but I don't do anything to block all the other androgens, I should
regrow 50% of my hair... at least according to the theories or ideas you
have sometimes put forward here.

But we know that doesn't happen, either.

We can't say that DHT is only responsible for less than a 50% contribution
to MPB, because that would mean it's no longer the "major" cause of MPB,
right?

But we know that even when people have ALL, or almost all, androgens
blocked, the vast majority don't regrow all their hair or anything close to
it. (I realize you said you did when you used RU, and I'm not discounting
that or doubting it... it may be true and you're just a fluke, and there is
probably a really valid biochemical reason for what happened to you... and
it probably does have to do with blocking all the androgens... but what I
am saying is that if this were found to be possible in a sizable number of
people, lots of people would already be doing it and it would be considered
a de facto cure for MPB.)

What I'm saying is that the real way to reverse hair loss is probably
downstream of all that androgen stuff. It doesn't mean androgens aren't
responsible. Androgens are very definitely responsible; you wouldn't get
bald if it weren't for androgens.

What I'm saying is that in the vast, vast majority of cases, you can't
reverse MPB to any reasonable extent by just blocking androgens (whether
it's DHT, testosterone, or any combination of androgens... including all of
them.) You have to block something else.

That's why I think there's a biochemical choke point involved here and I
think that it's a one-way genetic switch at the PGD2 Synthase gene. It is
most likely stimulated by DHT and/or other androgens, like testosterone
(most strongly by DHT, though.) When this switch is activated, it causes
PGD2 Synthase crank out ridiculous amounts of PGD2, which basically puts
people's follicles into a coma by gradually shortening the anagen phase and
dragging out the telogen phase.

Removing or blocking one, two, or all the androgens is generally enough to
stop further hair loss but, in almost all cases, it is NOT ENOUGH to
actually reverse the follicle miniaturization process to any significant
degree. The only way to reverse that biochemically is by blocking or
negating the PGD2 somehow, or by blocking or inactivating the enzyme.




jarjarbinx is located in [NA] and he is available to meet: NO


Post reply
jarjarbinx

17.10.2012, 20:35

@ jarjarbinx

oops no text

i said no text




jarjarbinx is located in [NA] and he is available to meet: NO


Post reply
roger_that

MARYLAND,
18.10.2012, 18:28
(edited by roger_that, 18.10.2012, 18:57)

@ jarjarbinx

It's not a distraction. It's a key point.

Based on my experience with 5-alpha reductase inhibitors and anti-androgens
I would say that it does not work the way you are thinking.

My illustrations about different percentage contributions of different androgens (e.g., 75% for DHT, 25% for testosterone etc), were actually intended to prove the opposite of what you probably think I was saying. I was trying to illustrate that even if you remove/block ALL the androgens (as you advocate), you still don't get a major reversal of your hair loss. So your theory can't be completely true.

I was trying to show that something else is needed, i.e., you need to block PGD2.

If my theory is correct and DHT induces PGD2 Synthase by way of a one-way gene switch, even if you eliminated ALL androgens from a balding person's head (by way of anti-androgens or whatever... including castration), that person would still not grow back all his lost hair, because many of the one-way switches (there are millions of them) will have already been turned on from previous exposure to DHT, and by definition, one-way switches cannot be turned off by removing or neutralizing the trigger that turned them on.

So I think you have to modify your theory, and for the third part, reversing hairloss, you need to say that in addition to blocking androgens, you need to block the PGD2 that's already being formed in the follicles, regardless of whether the androgens are all blocked or not.




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
jarjarbinx

18.10.2012, 21:24

@ roger_that

It's not a distraction. It's a key point.

where is the evidence that if you ALL androgen you don't grow back hair? I have experienced the opposite. When I used finasteride I slowed down the losses but when I used RU58841 in combo with rogaine 5% I got back a lot of hair. Now, keep in mind that I still have a lot of hair - I'm missing about 50% of my hair so I am not completely bald, I do not have any shiny bald skin on my head, and I still have peach fuzz in my bald areas. I am not saying that a shiny bald man will get regrowth if he uses a strong antiandrogen. It depends on how far advanced his hair loss is, how old he is, and how long he has been dealing with balding. I'm at stage 4 and I'm confident that I would get my hair back if they came up with a cure. But there are guys who have been balding too long, and the process has gotten too far advanced, who will never get their hair back.


Based on my experience with 5-alpha reductase inhibitors and
anti-androgens
I would say that it does not work the way you are thinking.

My illustrations about different percentage contributions of different
androgens (e.g., 75% for DHT, 25% for testosterone etc), were actually
intended to prove the opposite of what you probably think I was saying. I
was trying to illustrate that even if you remove/block ALL the
androgens (as you advocate), you still don't get a major reversal of your
hair loss. So your theory can't be completely true.

I was trying to show that something else is needed, i.e., you need to block
PGD2.

If my theory is correct and DHT induces PGD2 Synthase by way of a one-way
gene switch, even if you eliminated ALL androgens from a balding person's
head (by way of anti-androgens or whatever... including castration), that
person would still not grow back all his lost hair, because many of the
one-way switches (there are millions of them) will have already been turned
on from previous exposure to DHT, and by definition, one-way switches
cannot be turned off by removing or neutralizing the trigger that turned
them on.

So I think you have to modify your theory, and for the third part,
reversing hairloss, you need to say that in addition to blocking androgens,
you need to block the PGD2 that's already being formed in the follicles,
regardless of whether the androgens are all blocked or not.




jarjarbinx is located in [NA] and he is available to meet: NO


Post reply
AleMB81

19.10.2012, 04:19

@ jarjarbinx

It's not a distraction. It's a key point.

It seems to me that what roger_that says makes sense. It's quite obvious that DHT can not be the only responsible for hair loss. Once someone is castrated will stop his hair loss, however he needs oral anti-androgens for seeing hair regrowth.

As Roger_that says follicles are put into coma and they are not died. Indeed when you take strong meds you see some vellus regrowthing.

Moreover please note that smaller follicles can regrowth terminal hair in the proper conditions:
http://www.ncbi.nlm.nih.gov/pubmed/12734505

Probably we need to act against the real follicle killers on a topical level(I mean PGD2) because it seems barely impossible to stop all the androgens.




AleMB81 is located in [NA] and he is available to meet: NO


Post reply
roger_that

MARYLAND,
19.10.2012, 07:40

@ AleMB81

It's not a distraction. It's a key point.

It seems to me that what roger_that says makes sense. It's quite obvious
that DHT can not be the only responsible for hair loss. Once someone is
castrated will stop his hair loss, however he needs oral anti-androgens for
seeing hair regrowth.

I am not exactly saying that DHT is not the only thing responsible for hair loss. I am saying, all the evidence we have indicates that DHT is responsible for high levels of PGD2. Elevated levels of PGD2 do not happen spontaneously, out of thin air. PGD2 is directly in the chain of causation triggered by DHT.

What I am saying is that you have different opportunities to block this whole process. Blocking DHT itself is not enough, you have to also block the main consequence of DHT, which is PGD2.

The reason that blocking DHT alone doesn't reverse the process may be because of the one-way genetic switch that I described. This is only a working hypothesis, but I think it's a logical one.




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
AleMB81

19.10.2012, 08:53

@ roger_that

It's not a distraction. It's a key point.

What I wanted to say is that DHT is not the only responsible for hair loss since it only transfers a message. The "material killer" of the hair follicle is PGD2.. However now we have to wait the experiments with OC000459 to see if all the theory is true...

Let's hope...




AleMB81 is located in [NA] and he is available to meet: NO


Post reply
jarjarbinx

19.10.2012, 13:37

@ AleMB81

It's not a distraction. It's a key point.

There is some confusion because what you are saying agrees more with what I'm saying than what roger_that is saying. You need to go back and re-read the posts again because you are saying you agree with roger_that but in reality you disagree with roger_that.



It seems to me that what roger_that says makes sense. It's quite obvious
that DHT can not be the only responsible for hair loss. Once someone is
castrated will stop his hair loss, however he needs oral anti-androgens for
seeing hair regrowth.

As Roger_that says follicles are put into coma and they are not died.
Indeed when you take strong meds you see some vellus regrowthing.

Moreover please note that smaller follicles can regrowth terminal hair in
the proper conditions:
http://www.ncbi.nlm.nih.gov/pubmed/12734505

Probably we need to act against the real follicle killers on a topical
level(I mean PGD2) because it seems barely impossible to stop all the
androgens.




jarjarbinx is located in [NA] and he is available to meet: NO


Post reply
Mr. Z

19.10.2012, 14:14

@ roger_that

It's not a distraction. It's a key point.

Thanks for putting together this information, RogerThat. Good stuff!

Do you happen to know the mechanism that cetirizine works through? Does it inhibit PGD synthase or is it binding to the receptor CRTH2? Something else?




Mr. Z is located in [NA] and he is available to meet: NO


Post reply
AleMB81

19.10.2012, 14:50

@ jarjarbinx

It's not a distraction. It's a key point.

Really? Oh gosh I'm getting older however you understand my point of view:

1) DHT is a messenger, PGD2 is the follicle killer

2) Follicle does not die (or better not due to DHT)

3) Inibhiting the androgens wont't be as good as killing the PGD2 or its receptor




AleMB81 is located in [NA] and he is available to meet: NO


Post reply
roger_that

MARYLAND,
20.10.2012, 09:06
(edited by roger_that, 20.10.2012, 09:45)

@ jarjarbinx

It's not a distraction. It's a key point.

There is some confusion because what you are saying agrees more with what
I'm saying than what roger_that is saying. You need to go back and re-read
the posts again because you are saying you agree with roger_that but in
reality you disagree with roger_that.

He's not really saying that there are things other than DHT which are INITIALLY responsbible for most of MPB. He was trying to say that just targeting DHT alone is not enough, but he put that statement in a much simpler and abbreviated form because I believe English is not his main language. Still, I'm not criticizing him on that. He writes English quite well -- better than many who post here.

I am in agreement with you, jarjar, on the fact that other androgens definitely play a role in MPB and contribute to it. The point is that you seem to be implying that if you just make sure you block ALL the androgens, that will grow everyone's hair back. I don't think that's the case. It may have been the case for you because when you used RU58841, you were in an early stage of hair loss. I think for most cases which are more advanced or worse than yours, even blocking all the androgens would probably not restore all or most of the hair.

Let's face it, if what you say about RU is true, then it would by now be a widely acknowledged cure for MPB and some big pharma company or research group somewhere would have put it on track for FDA approval. The product has been "out there" for a long time. Obviously there's some reason it hasn't been leveraged as a complete or partial cure. Unacceptable side-effects might be one reason, but I'm just guessing because I haven't used the product.




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
AleMB81

20.10.2012, 10:19

@ roger_that

It's not a distraction. It's a key point.

There is some confusion because what you are saying agrees more with
what
I'm saying than what roger_that is saying. You need to go back and
re-read
the posts again because you are saying you agree with roger_that but in
reality you disagree with roger_that.

He's not really saying that there are things other than DHT which are
INITIALLY responsbible for most of MPB. He was trying to say that just
targeting DHT alone is not enough, but he put that statement in a much
simpler and abbreviated form because I believe English is not his main
language. Still, I'm not criticizing him on that. He writes English quite
well -- better than many who post here.

I am in agreement with you, jarjar, on the fact that other androgens
definitely play a role in MPB and contribute to it. The point is that you
seem to be implying that if you just make sure you block ALL the androgens,
that will grow everyone's hair back. I don't think that's the case. It
may have been the case for you because when you used RU58841, you were in
an early stage of hair loss. I think for most cases which are more
advanced or worse than yours, even blocking all the androgens would
probably not restore all or most of the hair.

Let's face it, if what you say about RU is true, then it would by now be a
widely acknowledged cure for MPB and some big pharma company or research
group somewhere would have put it on track for FDA approval. The product
has been "out there" for a long time. Obviously there's some reason it
hasn't been leveraged as a complete or partial cure. Unacceptable
side-effects might be one reason, but I'm just guessing because I haven't
used the product.

Exactly Roger, English is not my mother tongue language since I'm italian and sometimes it's hard for me to express all that I want to say. However what you say it's true. I don't believe that DHT is the only responsible and moreover I believe it's much better to erase all the negative prostaglandin than androgens (of course if possible).




AleMB81 is located in [NA] and he is available to meet: NO


Post reply
KO

21.10.2012, 01:20

@ roger_that

PGD2 linked to DHT - and how to reverse hair loss

First of all I want to post this:

http://www.genecards.org/cgi-bin/carddisp.pl?gene=PTGDS

Which is a link to a "gene card", sort of like a baseball card for human
genes, which shows all the relevant info and stats on the enzyme PGD2
Synthase. This is the one and only enzyme in the human body which
synthesizes the prostaglandin called PGD2.


This is a very very good post and definitely something to chew on.




KO is located in [NA] and he is available to meet: NO


Post reply
neversaynever

21.10.2012, 07:21

@ KO

PGD2 linked to DHT - and how to reverse hair loss

Good thread (for a change!).

In theory this PGD2 stuff is exciting, but there is yet to be a single shred of evidence that it can halt or reverse the human balding process. PGd2 might be the final hair killer (with DHT just dishing out signals to cells). But to regrow hair, the other PG's are vital. I think they are PGE2 and PGf2a? I think I read somewhere (maybe in a Dr Cots study) that PGE2 levels are also abnormal in balding areas? (too low). So some more things to talk about in terms of hair regrowth...

What happens to the other PG levels if PGD2 is blocked? Do E2 and f2a levels directly depend on pgd2 levels? Why are PGE2 levels lower in bald areas? It also makes sense that PGd2 plays a big part in sending follicles into the resting phase, what if blocking PGd2 triggers a reaction to produce it by non-DHT means. In the same way the body can generate extra sensitive DHT receptors or even create new ones.

If the PG's role in hair follicles are to regulate between resting and growth phases, it would make sense that as well as blocking PGD2, we need to signal hairs to grow using something else.

Brings me onto stuff like Histogens HSC. They claim to be achieving amazing regrowth in very short periods. As far as I know they're not directly interacting with PGD2. Their cocktail is obviously sending the right signals (which would usually be sent by PGE2?). So maybe its a combination of HSC + PGD2 blocking that we need.




neversaynever is located in [NA] and he is available to meet: NO


Post reply
Amilcar

08.11.2012, 20:12

@ roger_that

PGD2 linked to DHT - and how to reverse hair loss

Hello,

I have a question

If the Hair loss is believed to be areas related , in the Cotsarelis study, PG2 are higher in squares where Hairloss is occuring, how can we explain the fact that HT surgeons are able to regrow hair in bald areas which are supposed to already have high levels of PG2 ? In other words, if MPB is area related and not hair follicle related THEN the new seeded hair follicles should fall too right ????




Amilcar is located in [NA] and he is available to meet: NO


Post reply
roger_that

MARYLAND,
08.11.2012, 21:01

@ Amilcar

PGD2 linked to DHT - and how to reverse hair loss

If the Hair loss is believed to be areas related , in the Cotsarelis study,
PG2 are higher in squares where Hairloss is occuring, how can we explain
the fact that HT surgeons are able to regrow hair in bald areas which are
supposed to already have high levels of PG2 ? In other words, if MPB is
area related and not hair follicle related THEN the new seeded hair
follicles should fall too right ????


VERY good question and this issue has been raised before in other contexts (not specifically relating to PGD2).

I think the answer to that is that the assumption that it's not follicle-related is false. That is the assumption you're making but in Dr. Cotsarelis' research, there is nothing that really supports that assumption.

MPB can be both area-related and follicle-related, by virtue of the fact that follicles only in a certain AREA are affected.

Also remember that PGD2, as a prostaglandin, has some chemical properties such as being effective only in the precise local area where it is synthesized. PGD2 molecules are "used up" very very quickly after they're synthesized (within seconds), and don't travel any distance from point A to point B to do their work. Think of it this way: they are very fragile molecules that have a very strong desire to react with something immediately after they're synthesized. Therefore they only act locally.

At the sub-microscopic scales we're talking about, "locally" means within several nanometers (1 nanometer = 1 billionth of a meter)... maybe less than that.

Remember the place where the PGD2 Sythase is active (according to the radiographic photos shown by Dr. Cotsarelis), creating the PGD2, is not in-between follicles, but INSIDE the follicles themselves, in the very cells of the follicle... Look at the photo...

[image]

The active PGD2 Synthase enzyme here is green.

For a PGD2 molecule to move from a balding follicle where it was made to a transplanted follicle, and still remain intact, would probably be impossible. The molecule would be destroyed by reacting with something long before it left the follicle where it was synthesized.




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
jarjarbinx

08.11.2012, 21:37

@ Amilcar

PGD2 linked to DHT - and how to reverse hair loss

Hello,

I have a question

If the Hair loss is believed to be areas related , in the Cotsarelis study,
PG2 are higher in squares where Hairloss is occuring, how can we explain
the fact that HT surgeons are able to regrow hair in bald areas which are
supposed to already have high levels of PG2 ? In other words, if MPB is
area related and not hair follicle related THEN the new seeded hair
follicles should fall too right ????


That's a very good question. There are some questions that still need to be answered.




jarjarbinx is located in [NA] and he is available to meet: NO


Post reply
hairman2

09.11.2012, 05:42

@ Amilcar

PGD2 linked to DHT - and how to reverse hair loss

Hello,

I have a question

If the Hair loss is believed to be areas related , in the Cotsarelis study,
PG2 are higher in squares where Hairloss is occuring, how can we explain
the fact that HT surgeons are able to regrow hair in bald areas which are
supposed to already have high levels of PG2 ? In other words, if MPB is
area related and not hair follicle related THEN the new seeded hair
follicles should fall too right ????


well, isn't the area affected by MPB, simply defined by the prevalent tissue. If you move tissue (i.e. follicles) from the back of your head to the top of your head, then you are introducing new tissue into the affected area.

Since this obviously works, the affects of PGD2 must either be quite localized or the new follicles resistant to it (i.e. less or no GPR44 receptors). It has also been suggested by someone in another forum that the PGD2 is actually produced in the very same cells which it affects. So to me it is conceivable that the newly introduced cells from the back of your head produce less PGD2 than the cells in the bald area of the scalp.

Also I agree with roger_that, that according to the literature PGD2 has a very short half-life (few seconds) and must therefor be quite localized, albeit probably more than just nanometers, but rather a micron or so (just guessing).




hairman2 is located in [NA] and he is available to meet: NO


Post reply
Amilcar

09.11.2012, 07:02

@ hairman2

PGD2 linked to DHT - and how to reverse hair loss

jarjabinx, hariman2 and roger_that Thank you for this. Do you think we can find some natural PG2/receptor inhibitor ??? And guess what tumric, Omega-3 Fatty Acids and Resveratrol are in the crowd http://www.chiro.org/nutrition/FULL/Natural_COX-2_Inhibitors.shtml

We used to think that Resveratrol is good for Hair/MPB due to its anti-inflammatory effects. Now, it seems there are other reasons for that and that some literature is citing Prostaglandins as a source of inflammation, So you will be fighting inflammation while inhibiting PG2 ?....

Latey, some one of you guys mentioned fish oil as part of all successful regimens. As you may know its rich in Omega3 fatty acids. I still recall posts from Brian in HLH where he used to talk a lot about Omega3 fatty acids and how they are Good to fighht MPB...




Amilcar is located in [NA] and he is available to meet: NO


Post reply
roger_that

MARYLAND,
09.11.2012, 07:48
(edited by roger_that, 09.11.2012, 08:08)

@ Amilcar

PGD2 linked to DHT - and how to reverse hair loss

jarjabinx, hariman2 and roger_that Thank you for this. Do you think we can
find some natural PG2/receptor inhibitor ??? And guess what tumric, Omega-3
Fatty Acids and Resveratrol are in the crowd
http://www.chiro.org/nutrition/FULL/Natural_COX-2_Inhibitors.shtml

I think this could be possible theoretically, but I don't have much faith in it. I have more faith in custom designed drugs -- they can be more precisely targeted.

We used to think that Resveratrol is good for Hair/MPB due to its
anti-inflammatory effects. Now, it seems there are other reasons for that
and that some literature is citing Prostaglandins as a source of
inflammation, So you will be fighting inflammation while inhibiting PG2
?....

I think the answer is that the 2 things are one in the same. In general, prostaglandins are involved in the inflammatory process, so it stands to reason that some anti-inflammatory drugs will reduce specific prostaglandins like PGD2.


Latey, some one of you guys mentioned fish oil as part of all successful
regimens. As you may know its rich in Omega3 fatty acids. I still recall
posts from Brian in HLH where he used to talk a lot about Omega3 fatty
acids and how they are Good to fighht MPB...

I have no idea about fish oil, and I tend to be very skeptical about any claim that a certain nutrient in foods can effectively "fight MPB". I think the proponents of nutrition as a way of preventing or slowing or stopping MPB are pretty much deluding themselves. It may have a nominal impact in impeding a bit of damage at the cellular level, but never a visible cosmetic impact.

Also, Bryan says a lot of things. I think the last time he came to this forum, he parachuted in here, made some snarky sarcastic criticisms of one of my big posts about PGD2 Synthase, and then when I asked him to explain, he disappeared just as quickly.

And my post was one that a lot of people here said was interesting and maybe very important in connecting the dots on MPB, and one new forum poster who is extremely knowledgeable commended me on.

I'm not saying Bryan isn't a smart guy, but I think he puts way too much stock in his own opinions, and a lot of the time his opinions are pretty idiosyncratic and outside of the mainstream of what scientists like Dr. Cotsarelis would tell you.




roger_that is located in MARYLAND and he is available to meet: YES
email hairsite@aol.com to arrange a meeting.


Post reply
cal

09.11.2012, 15:30

@ roger_that

PGD2 linked to DHT - and how to reverse hair loss

Existing food/drugs to block PGD2 -

IMO if there was anything that made a significant dent then people would have known about it centuries ago. Anything that helps us in a significant way will be artificially man-made and probably just invented within the last few decades or less.



Histogen -

Their more recent pics seem to show a much weaker result for the male patient than the two female ones.

Meanwhile, the PGD2 blocking theory we're kicking around here would provide a way to fight the most directly "male" part of the MPB problem, the effects of the androgen exposure.

I'm wondering if a combination of blocked PGD2 and Histogen injections might be more effective than the sum of its parts. Too bad we're probably looking at 2015+ before we have an answer.




cal is located in [NA] and he is available to meet: NO


Post reply
Amilcar

09.11.2012, 19:58

@ cal

PGD2 linked to DHT - and how to reverse hair loss

cal,

Do you know a single person that has been rubbing Green Tea/Fish oil daily on his scalp ?!

Existing food/drugs to block PGD2 -

IMO if there was anything that made a significant dent then people would
have known about it centuries ago. Anything that helps us in a significant
way will be artificially man-made and probably just invented within the
last few decades or less.



Histogen -

Their more recent pics seem to show a much weaker result for the male
patient than the two female ones.

Meanwhile, the PGD2 blocking theory we're kicking around here would provide
a way to fight the most directly "male" part of the MPB problem, the
effects of the androgen exposure.

I'm wondering if a combination of blocked PGD2 and Histogen injections
might be more effective than the sum of its parts. Too bad we're probably
looking at 2015+ before we have an answer.




Amilcar is located in [NA] and he is available to meet: NO


Post reply

Thread view  Order  «  
 
117704 Postings in 11208 Threads, 5302 registered users
Hair Loss Forum | Admin contact

 

Disclosure: This is an advertising site for our paid sponsors & advertisers. The contents, videos & photos on HairSite are provided by paid sponsors and are not endorsed by HairSite in any way. The recommendations, results, and representations made by our sponsors/advertisers do not reflect the opinions of HairSite. This site is to showcase successful hair restoration results only. It is not the mandate of this site to engage in the discussion of failed, unsuccessful procedures, lawsuits, litigations or complaint cases; comments of such nature, including external links, may be removed from the forum. Notify hairsite@aol.com any false, defamatory, misleading or inappropriate user generated contents for immediate removal from the forum. Also read Terms of Use & Privacy Statement |  HairSite advertisers: ASMED | Dr. Bhatti | Dr. Bisanga | Dr. Cole | Dr. Hakan Doganay | Dr.Epstein | Dr. Jones | Dr. Halder | Hasson & Wong | Dr. Klein | Dr. Madhu | Dr. Mwamba | Dr. Donald Ng| Dr. Poswal | Dr. Rahal | Dr. Razack | Dr. Reddy | Dr. Umar | Dr. Woods | DHI Global | HDC Clinic | |Lasercomb | Reviva Clinic | Ziering Medical|