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

J Cutan Pathol. 2013 Dec 19. doi: 10.1111/cup.12286. [Epub ahead of print]
A prostaglandin d-synthase-positive mast cell gradient characterizes scalp patterning.
Larson AR, Zhan Q, Johnson E, Fragoso AC, Wan M, Murphy GF.

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.

Well I hope this one doesn't go unnoticed. That is extremely telling of why the pattern of balding exists.

The question is, if this distribution occurs even in non-balding individuals, what is activating the mast cells in balding men vs. non-balding?

Gut integrity problems, lacking minerals and excess toxins sums it up I think.

The soils in organic and conventional alike often lack important minerals, some have been out of major circulation for 200 years. Add to to that toxins, stress, glyphosate, antibiotics and vaccines, it's quite a bit.

I was reading about the 'niacin flush' and how absorption of niacin elevates PGD2 expression. The hot flushes are caused by the vasodilatory effects of PGD2, so I wonder if the hot flushes in the balding areas of many hairloss sufferers are the result of elevated PGD2 and if they are related to niacin toxicity?

But why would higher levels of PGD2 be found in the vertex of the scalp? This is puzzling to say the least. Unless they are required to help dilate compressed capillaries and help maintain homeostasis.

Xenon wrote:I was reading about the 'niacin flush' and how absorption of niacin elevates PGD2 expression. The hot flushes are caused by the vasodilatory effects of PGD2, so I wonder if the hot flushes in the balding areas of many hairloss sufferers are the result of elevated PGD2 and if they are related to niacin toxicity?

But why would higher levels of PGD2 be found in the vertex of the scalp? This is puzzling to say the least. Unless they are required to help dilate compressed capillaries and help maintain homeostasis.

Long before PDG2 was a recognized factor in MPB, I had wondered about positive or negative effects of niacin. However, it's not quite as black and white of an issue. Niacin produces a flush initially, however it actually reduces allergic/mast cell production after and fuels the mitochondrial and acts as a potassium channel agonist (like minoxidil) or
helps maintain hair follicle diameter and helps boost the mood (especially with other B-vitamins in proper form).

I should mention however, that quecetin prevents a rise in PGD2 from niacin.

IDK if this is of any interest to you CS, AS54, or anyone else, but according to this study, it says that PGD2 is not mast cell derived, rather from a niacin responsive cell that resides in the skin. The study after this states that Langerhans cells within the skin release PGD2 in response to niacin.

I found both to be interesting:

Identification of skin as a major site of prostaglandin D2 release following oral administration of niacin in humans.

Oral administration of niacin (nicotinic acid) at pharmacologic doses that reduce serum cholesterol levels induces intense flushing in humans. We have recently shown that the vasodilation following ingestion of niacin is due to the release of prostaglandin (PG) D2. However, the site from which PGD2 is released is not known. It has previously been shown that topical application of methylnicotinate causes local cutaneous erythema. Thus, we investigated whether topical methylnicotinate causes a release of PGD2 locally from skin and the possibility that skin may be a major contributor to the release of PGD2 when niacin is administered by mouth. Topical administration of methylnicotinate (10(-1) M) to the forearms of human volunteers resulted in 58- to 122-times increases in levels of PGD2 and 25- to 33-times increases in levels of the metabolite of PGD2, 9 alpha,11 beta-PGF2, in blood drawn from the antecubital vein draining the treated sites. Increased levels of PGD2 and 9 alpha,11 beta-PGF2 were not found in blood drawn simultaneously from veins in the contralateral arm, indicating that the PGD2 was released from the site of methylnicotinate application. The release of PGD2 in response to topically applied methylnicotinate occurred in a dose-dependent manner over the concentration range of 10(-3) to 10(-1) M. The release of PGD2 was not accompanied by a release of histamine, suggesting that the release of PGD2 was not from the mast cell. Following oral ingestion of niacin, levels of PGD2 in superficial venous blood draining the skin were 14 to 1200 times higher than the level in arterial blood supplying the skin of the same arm. This finding indicates that the skin is a major site from which PGD2 is released following oral ingestion of niacin. These studies thus indicate that the cutaneous vasodilation that occurs following oral administration of niacin is primarily due to a release of PGD2 from a niacin responsive cell that resides in the skin.

http://www.ncbi.nlm.nih.gov/pubmed/1373750


LANGERHANS CELLS RELEASE PROSTAGLANDIN D2 IN RESPONSE TO NICOTINIC ACID.

Summary:

This study by researchers at Arena Pharmaceuticals demonstrated that MatTek’s Human Dendritic Cells can be used to identify the mechanism of a drug’s in vivo adverse side effects.

Nicotinic acid, used for atherosclerosis treatment, has an adverse effect of skin flushing. The flushing mechanism, thought to be caused by the release of prostaglandin D2 (PGD2), is not well understood.

In this study, researchers at Arena Pharmaceuticals attempted to identify which cells mediate the flushing effect.

Nicotinic acid receptor (GPR109A) gene expression was assessed in various tissues and cell lines. Cells expressing GPR109A mRNA were further assayed for PGD2 release in response to nicotinic acid.

Of all samples, only skin was able to release PGD2 upon stimulation with nicotinic acid. The responsive cells were localized to the epidermis, and immunocytochemical studies revealed the presence of GPR109A on epidermal Langerhans cells. CD34+ cells isolated from human blood and differentiated into Langerhans cells (hLC-L) from MatTek Corp. also showed GPR109A expression.

IFN ã treatment increased both mRNA and plasma membrane expression of GPR109A. IFN ã-stimulated hLC-Ls released PGD2 in response to nicotinic acid in a dose-dependant manner (effector concentration for half-maximum response=1.2mM±0.7). Acifran, a structurally distinct GPR109A ligand, also increased PGD2 release, whereas isonicotinic acid, a nicotinic acid analog with low affinity for GPR109A, had no effect.

These results suggest that nicotinic acid mediates its flushing side effect by interacting with GPR109A on skin Langerhans cells, resulting in release of PGD2.

http://mattek.com/425.-langerhans-cells-release-prostaglandin-d2-in-response-to-nicotinic-acid.

CS has pointed out before that zinc and quercetin are both potent mast cell stabilizers. The thing with zinc is that its such a ubiquitous mineral in the body (so many enzymes use it) that most people don't really ever get to true zinc sufficiency. They might get what's absolutely necessary, but sufficiency is different. I've taken 50 mg for a while now. I've known people to do 3 days to one week of loading with zinc, taking 100 mg daily. There were no problems.

I also think that this mast cell issue makes cromolyn/cromoglycic acid something to continue looking at. Obviously there are things like bimatoprost out there, but unless you've got the money to pay for enough for daily full scalp application, its impractical to even experiment with. Not to mention, I think the scalp skin is a different environment than the normal application of bimatoprost (eyelashes). I think cromolyn has a huge potential for application here, but we need a better vehicle to carry it.

P.S. I'd just like to touch upon a line from the latter study:

"CD34+ cells isolated from human blood and differentiated into Langerhans cells (hLC-L) from MatTek Corp. also showed GPR109A expression."

CD34+ cells are the progenitors involved in hair growth. So I wonder if the niacin receptors within these progenitors are involved in hairloss?

AS54 wrote:CS has pointed out before that zinc and quercetin are both potent mast cell stabilizers. The thing with zinc is that its such a ubiquitous mineral in the body (so many enzymes use it) that most people don't really ever get to true zinc sufficiency. They might get what's absolutely necessary, but sufficiency is different. I've taken 50 mg for a while now. I've known people to do 3 days to one week of loading with zinc, taking 100 mg daily. There were no problems.

I also think that this mast cell issue makes cromolyn/cromoglycic acid something to continue looking at. Obviously there are things like bimatoprost out there, but unless you've got the money to pay for enough for daily full scalp application, its impractical to even experiment with. Not to mention, I think the scalp skin is a different environment than the normal application of bimatoprost (eyelashes). I think cromolyn has a huge potential for application here, but we need a better vehicle to carry it.

Interesting, I never knew zinc played a role in mast cell stabilization... wonder if zinc loss from excessive masturbation has any effect upon this? I read somewhere that men can lose between 5 - 15mg of zinc from every ejaculation, I also read that PGD2 is involved in erectile function.

I guess if you take your zinc / quercetin supplements (as I don't), then there's nothing to worry about. BTW I hear that ginger inhibits COx-2 and PGD2, I might apply some topically... see how that works out.

CF wrote:

Xenon wrote:BTW I hear that ginger inhibits COx-2 and PGD2, I might apply some topically... see how that works out.

https://immortalhair.forumotion.com/t9183-6-gingerol-inhibits-hair-shaft-growth-in-cultured-human-hair-follicles-and-modulates-hair-growth-in-mice

Thanks for the heads up.

No problem.

I think a water-soluble mixture of cromolyn sodium and quercetin-chalcone would be incredibly interesting to try.

Cromolyn sodium has been used for several mast cell diseases with a lot of success. These applications were primarily for histamine mitigation, but if we're stabilizing mast cells, we'd be lowering PGD-2 at the same time.

I'm not sure where to get my hands on the cromolyn though. You can get it through nasalcrom, but I'm not sure what the dilution is for that.

You can get cromolyn drops from any pharmacy. It's for eye allergies. But it comes in a small dropper bottle and is pretty expensive.