A PGD synthase-positive mast cell gradient characterizes scalp patterning

[maher]

At least we now know where "the pattern" comes from.. damn!

A PGD synthase-positive mast cell gradient characterizes scalp patterning:

"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.

http://www.ncbi.nlm.nih.gov/pubmed/24438498



The mast cells is a "major storage site for histamine":

http://www.annualreviews.org/doi/abs/10.1146/annurev.pa.23.040183.001555?journalCode=pharmtox

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IMO, this is very important discovery. Answers a lot of questions.

 

[abcdefg]

Good. Give me treatment

 

[Python]

At least we now know where "the pattern" comes from.. damn!

A PGD synthase-positive mast cell gradient characterizes scalp patterning:

"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.

http://www.ncbi.nlm.nih.gov/pubmed/24438498



The mast cells is a "major storage site for histamine":

http://www.annualreviews.org/doi/abs/10.1146/annurev.pa.23.040183.001555?journalCode=pharmtox

- - - Updated - - -

IMO, this is very important discovery. Answers a lot of questions.

Interesting, what you think is the scalp of people with something like DUPA.

 

[maher]

Mast cell stabbilizer:

http://en.wikipedia.org/wiki/Mast_cell_stabilizer

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033805

"
Quercetin:Effect on contact dermatitis and skin photosensitivity in humans

Patch tests conducted with nickel in 10 volunteers showed extensive dermatitis ranging from 1+ to 3+ at 48 hr and 120 hr after nickel contact (Fig. 5A&B). Pre-administraiton of WSQ (2 g/day for 3 days) before nickel contact on the same volunteers effectively reduced this reaction by more than 50% in 8 out of 10 patietns, and 100% in the other 2 patients (Fig. 5A&B, Wilxocon paired non-parametric test, p = 0.039 for 48 hr, and p = 0.031 for 120 hr after nickel contact). Moreover, any associated pruritus disappeared as did the generalized pruritus present in one patient with pre-exsiting atopic dermatitis"

 

[bushbush]

This study has been floating around some other forums for a while. It gives support to the PGD2 theory and helps dispel some of the more crackpot theories like gravity being responsible for patterning.

 

[IDW2BB]

So does this mean that transplanted hairs from the donor survive in the recipient area because of this instead of them being androgen resistant?

 

[maher]

So does this mean that transplanted hairs from the donor survive in the recipient area because of this instead of them being androgen resistant?

That could be. Thats the first thing that crossed my mind- mast cells from back of the scalp are immuno-inactive.

 

[benjt]

Very interesting. Some resulting questions: Why are there more mast cells in Androgenetic Alopecia/male pattern baldness patients' scalps? Where are mast cells usually produced? What can elevate mast cell production? How can mast cells be reduced or made inactive?

 

[I.D WALKER]

If I have it correct I believe mast cells are predominantly generated in our bone marrow and act in the best interest of our immune system. Perhaps mast cell proliferation in the occipital scalp region is yet another immune response or byproduct of micro/macrocellular inflammation that once more will require more concentrated research in order to flesh out the root and mechanism.

 

[benjt]

Are all or most mast cells really produced in the bone marrow and then only delivered to local sites? How are they summoned by local sites, if they are only centrally produced? I tried googling into the matter, but could not find much conclusive stuff. There are definitely mast cells generated by/from bone marrow, but I don't know if that is the predominant production.

Mast cells are, as far as I know, not the byproduct of inflammation, but they are the first step in the inflammation process. I think it goes like this:
1. mast cell triggered
2. histamine released
3. PGDS/COX elevated
4. PGD-2 elevated

If I'm wrong, please correct me, but as far as I know that is the rough sketch of the inflammatory process.

 

[maher]

This is complicated.

Dog study:

"Stem cell factor (SCF) influences mast cell activation and inflammatory mediator release, and is elevated in tissues undergoing allergic inflammation.

These experiments suggest that dermal SCF secretion could potentiate histamine release following IgE receptor cross-linking and thus, could be one of the explanations for the inherent mast cell hyperexcitability observed in canine atopic dermatitis."

http://www.ncbi.nlm.nih.gov/pubmed/11844224

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Mast cells derive from hematopoietic progenitors and mature in tissues depending on microenvironmental conditions [1], [2]. Mast cells are important effector cells in allergic reactions [3]–[6] by secreting histamine, leukotrienes (LTs), prostaglandin D2 (PGD[SUB]2[/SUB]), proteolytic enzymes and several multifunctional cytokines, such as interleukin-6 (IL-6), IL-8, IL-13, tumor necrosis factor (TNF), and vascular endothelial growth factor (VEGF) [7]–[9]. These mediators contribute to the late-phase reactions and to inflammation through the recruitment and activation of immune cells [10], [11]. In addition to IgE and antigen, anaphylatoxins, cytokines, hormones and neuropeptides, such as substance P (SP), can trigger mast cell secretion [12] of several mediators often selectively [13]. More importantly, SP has been implicated in many skin inflammatory disorders, including contact dermatitis [14], [15]. As a result, mast cells are also involved in innate and acquired immunity [16], as well as autoimmunity and inflammation [12], especially in the skin [17], [18]. Mast cells were also shown to be involved in contact dermatitis in mice.

 

[Python]

Are all or most mast cells really produced in the bone marrow and then only delivered to local sites? How are they summoned by local sites, if they are only centrally produced? I tried googling into the matter, but could not find much conclusive stuff. There are definitely mast cells generated by/from bone marrow, but I don't know if that is the predominant production.

Mast cells are, as far as I know, not the byproduct of inflammation, but they are the first step in the inflammation process. I think it goes like this:
1. mast cell triggered
2. histamine released
3. PGDS/COX elevated
4. PGD-2 elevated

If I'm wrong, please correct me, but as far as I know that is the rough sketch of the inflammatory process.

Where does DHT fit in your theory. If it's mostly about inflamation then the best drug should be more about stoping inflamation rather then stopping localize DHT?

On another note, since you seem to know your stuff, do know if hairloss makes the scalp touch sensative, like it hurts when I rub my scalp. Is that something that you have come across? Since I have been losing more hair, it feels more sensative an painful. I don know it's because I have some form of DUPA or is just the alcohol in minoxidil, but I have been using it for years and it got worse now that I lost a lot of hair. Thanks in advance if you respond.

 

[benjt]

I'm not entirely sure where DHT fits in here. Elevated DHT is definitely connected with elevated COX-2. See this post for a couple of confirmed connections between DHT and inflammatory response mechanisms which might be lacking intermediate steps though. So perhaps the cause of action is DHT -> mast cells -> histamine -> COX/PGDS. I'm not too sure about this, maybe someone else (like a biologist - you know who you are ) could shed some light.

DHT is also in general associated with a more aggressive immune system. Uneducated guess: Maybe DHT is responsible for the mast cells?

 

[maher]

Mast cells contain androgen receptors.

 

[brunobald]

A good explaination of mast cell function in inflammation

http://www.youtube.com/watch?v=GGXg6jf6Phk

 

[benjt]

Mast cells do contain androgen receptors, but according to http://www.ncbi.nlm.nih.gov/pubmed/19758318 they do not degranulate upon treatment with T. Question is whether they would degranulate when DHT is given.

However, it is actually dermal papilla cells in bald(ing?) scalp that have higher androgen receptor expression (source: http://www.ncbi.nlm.nih.gov/pubmed/21167691 ), which is also a pretty good candidate for a significant difference between people suffering from Androgenetic Alopecia/male pattern baldness vs people not suffering from it - while I don't know if mast cell AR expression is higher or not.

Also, given how androgens strengthen the immune system, the mast cells on Androgenetic Alopecia/male pattern baldness scalp could (only a hypothesis here!) be a side effect of the very high DHT levels. After all, in bald(ing) scalps you don't only have AR overexpression, but also extremely high levels of 5αR.
Additionally take into account that PGs are involved in hair cycling, so perhaps the mast cells are actually supposed to be there anyway. It would make for a very plausible explanation of their presence, assuming that the body uses them to release the PGs for hair cycling. After all, the study says: "This difference was present in both balding and non-balding scalps and was independent of gender." If these mast cells are present both in people with and without Androgenetic Alopecia, I don't think they'd make a good target for treatment, as they are not the key difference (or any at all) between people with and without Androgenetic Alopecia/male pattern baldness.

 

[drgs]

Luteolin inhibits mast cells
I had a bottle of pills which I threw out, and now regret

So does quercertin