Seborrheic alopecia linked to MPB and destruction of vital progenitor cells?

OK, I was debating some time back about the acidic properties of sebum and how a build up of it within the follicle can cause inflammation. Well, I happened to notice that the sebaceous gland is located directly above the hair bulge -- the region which houses vital progenitor cells required for hair growth. progenitor cells are basically involved with the production of matrix cells -- cells located around the papilla and they assist it in producing thick terminal hair.

Anyway, i realized something which may be of major importance here: because sebum is produced directly above the hair bulge, if it comes into contact with this region and remains there for a considerable length of time, then it's acidic properties (pro inflammatory fatty acids) will begin to inflame the bulge and vital progenitor cells will be destroyed.

If you have gone without washing your hair for a few days, then you will recall how greasy your scalp becomes and you will also likely experience a stinging sensation throughout your scalp. This is inflammation caused by the fatty acids. So, it's very likely during this process, that progenitor cells within the hair bulge are also being destroyed.

Sebum is a substance recognized in causing baldness, and it is termed seborrheic alopecia. I think that the reason is because of inflammation caused to the bulge region, although the medical community state that they believe it is because it clogs up the hair shaft (yes, partially, but the damage is caused by it's acids).

BTW I'm not citing this as the #1 cause of baldness, as it is apparent that the condition is induced in many ways in different individuals, but I definitely believe that this is a contributory factor.

I suggest you google the sebaceous gland and the hair bulge, and you will find that they are very close together, then you will have a better picture of what i am getting at.

ETA: the inflammatory effects of sebum may be more marked in men because it is said that testoterone, esp DHT, causes the sebaceous glands to produce much more sebum.

What are your thoughts on toxins, etc in the sebum itself?

I only ask because the dermatologists that are researching scarring alopecia have found problems with fatty acid metabolism in scarring alopecia (and I guess people with AGA probably have some sort of fatty acid metabolism dysfunction also) and it's deemed to be an autoimmune condition where the sebaceous glands are being attacked until they die. I think in their lastest study they were trying to find out if maybe the sebum itself was toxic causing an immune response, or if hair could not survive without the sebaceous gland.

I found this interesting because all alopecias have been linked to auto immunity. To me the patterns of loss can appear similar, like frontal fibrosing alopecia appears almost like MPB (except involves the side burns area, eyebrows and eyelashes). This is also known to respond to dutasteride (however, occurs mostly in post menopausal women).

Missy, as I understand it, the acids in sebum are there to destroy bacteria on the skin. Sebum forms into a layer on the skin called the acid mantle,

In acne, the skin becomes inflamed due to a build up of acidic sebum, and if severe enough, it will impair protein structures and leave scarring. In some acne sufferers, the scarring leaves them with bald patches in the beard. So I believe that the same can definitely happen in scalp hair if too much of it builds up.

Not only do I think it attacks the hair bulge, but it may penetrate to the lower levels of the follicle where the dermal papilla and hair producing matrix cells are located, and it likely inflames them.

I have read about many hairloss sufferers who report their hair becoming extremely greasy - prior to them losing their hair. Again, the excess production of sebum is apparently caused by overproduction of DHT. Perhaps because DHT anabolizes cells within the gland and causes them to overproduce sebum. perhaps.

As far as toxins go, I personally think that due to the skin of the scalp or galea region being much tighter than everywhere else, then circulation is hindered and thus toxins build up and remain within the cytoplasm or cell wall much much longer. I think that this is the reason why immune activity seems to be heightened in this region, hence the increased inflammation experienced by many hairloss sufferers. As you stated, "all alopecias have been linked to auto immunity". I completely agree, and there seems to be a myriad of causes for inflammation.

I never actually knew that the sebaceous gland was attacked by the immune system (or that it died). Perhaps this may be because it overproduces acidic sebum, due to steroid hormones.

Thanks for the info. I'll look into this.

Now as I understand it, that inflammation has less to do with the pH of the sebum in general, and more to do with the commensal bacteria/yeasts of the skin which feed on the fatty acids in sebum. Arachidonic acid is produced during this process and eventually leads to the production of the bad prostaglandins we want to stay away from. Arachidonic acid is also not a fatty acid you want floating around in high amounts, it makes for instability in cell membranes and probably perpetuates mast cell degranulation, leading to even more arachidonic acid.

Where did you read that commensal bacteria feeds on these acids? i read that the acid mantle formed from sebaceous acids is designed to prevent the build up of bacteria on the skin.

i read that increased inflammation of the follicle wall causes an increase of shedding in dead cells, which then creates an environment for propionibacterium to thrive. Apparently, propionibacterium proliferates in the papilla area, which then leads to an inflammatory response, hence destruction of vital matrix cells. But from what I have read, sebum generally prevents this gram positive bacteria from building up, so I am puzzled at your statement that this bacteria feeds on sebum fatty acids.

In regards to arachidonic acid, how is it produced during this process? i know that a diet consisting of meat, eggs and dairy cause higher production of it, but fail to see how it forms during the process by which you describe... but I'm open to you explaining it to me.

P. acnes is the main species I'm referring to, and it is responsible for the pathology of acne. But in my mind, hair loss is highly related. Other forms of yeast, like melasezzia also contribute.

But P. acnes is an anaerobe who can tolerate oxygen but this is why it tends to form biofilm deep in hair follicles, particularly those which produce high amounts of sebum, which minimizes the oxygenation and makes it more habitable for the bacteria. There is evidence that P. acnes can cause increased sebum production. P. acnes enzymatically digests sebum fatty acids and triglycerides to conjugated fatty acids and propionic acid (where the P in their name comes from). This metabolic activity can produce lipoperoxides that are in and of themselves inflammatory but also trigger the inflammatory response. In addition, the success of steroidal antiinflammatories against acne suggests some type of activity of arachidonic acid, perhaps as part of the immune response. I didn't really state it correctly by saying p acnes produces arachidonic acid. It tends to produce more short chain fatty acids. Rather, the immune response to the bacteria and its metabolic byproducts probably results in increased arachidonic acid and other mast cell products like PGD2.

But diet plays an important role in sebum production and concentration, with high fat diets and high carbohydrate diets both shown to alter amount and composition of sebum. Particularly, insulin and IFG are really important for sebum production. While we may never be able to alter our own immune response to commensal bacteria, we can certainly alter the microenvironment...eat a healthier profile of fats and minimize our baseline insulin levels.

But yes, sebum does have its own inflammatory effects, meant to help sterilize the skin surface, and it also works to balance the levels of oxidants-to-antioxidants in the skin, suggesting that there may be a lack of fat-soluble antioxidants in patients with inflammatory skin conditions. But there are organisms that have evolved, like p acnes, to thrive in this environment. There is something to fill every niche.

In fact, now that I think about it, the proliferation of aneorobes like p acnes could be connection between a lack of circulation and hair loss....after all, a lack of circulation would mean less oxygen and a more habitable environment for them. Just spitballing, but its interesting.

But diet plays an important role in sebum production and concentration, with high fat diets and high carbohydrate diets both shown to alter amount and composition of sebum

I read more into the kinds of fatty acids contained within sebum. Many sources point to Oleic acid as the culprit for causing inflammation and major shedding of the follicle wall. Given the close proximity of the hair bulge to the sebaceous gland, I personally think Oleic acids directly inflame this area and may cause progenitor cells to diminish.

"When there is an imbalance of available Omega 3 and 6 essential fatty acids, the sebaceous glands produce sebum with another fatty acid, oleic acid. Oleic acid produces sebum that is firmer. It is also irritating to the follicle lining which promotes irritation and excessive cellular debris."

ETA: DHT promotes higher sebum production, and on that merit, more Oleic acid.

I read a study recently where recombinant bacterial species given certain isomerases from p acnes were far less viable when their diet included a lot of monounsaturated fatty acids. This whole aspect of things is worth looking at in my opinion, and finding how the sex steroids tie in, perhaps through sebum like you mentioned, is also necessary.

Look at this diagram showing the bulge beneath the sebaceous gland

http://www.pnas.org/content/100/suppl.1/11830/F2.large.jpg



The follicle depends upon the store of progenitor cells in order for terminal hair cells to be produced in the matrix - surrounding the papilla. Now oleic acid would certainly come into contact with the bulge wall if there was an overproduction of sebum, and it would definitely cause it to inflame. If this process is ongoing, then the bulge would likely be destroyed and progenitor cells would no longer be produced. The result, of which, would be a discontinuance in production of terminal hair cells within the papilla. In short, if the bulge is destroyed, then terminal hair cannot be produced, period.

I also think that pure destruction of the bulge might not be so much of an issue as improper hyperproliferation of keratinocytes is. Its part of the wound healing mechanism which seems to be deranged in male hairloss and one of the reasons, in addition to collagen deposits, that we see the scarring that goes on with mpb. So perhaps its that the keratinocytes aren't migrating to the papilla and being utilized in formation of new shaft structure as much as they are being deposited into the root sheath, cause the shaft itself to begin thinning more and more with each new hair produced.

The thing is, keratinocyte stem cell production is dependent upon the existence of progenitor cells within the bulge. If there is no PC's, then there will be no keratinocytes produced.

I wonder if poor blood circulation results in low migration of progenitors to the hair bulge also? i can't say for certain, but there's so much speculation about poor blood circulation and hairloss, that there might just be a link.

I was looking at minoxidil and how it apparently causes some regrowth, and several sources believed that it worked by acting as a vasodilator to capillaries, as to allow greater oxygen and nutrient delivery. Perhaps this vasodilating effect allows a greater number of progenitor cells to migrate to the hair bulge, also? I say this because how else could hair start to regrow? Minox must assist in allowing easier migration of PC's to the bulge.

See, if there is a problem with PC's migrating to the bulge, then when the follicle is being inflamed, there might not be enough PC's within the bulge to regenerate the matrix region. And if the site is under chronic inflammation, then the matrix will just continue to degenerate worse.

Anyway, I was reading a study about the hair bulge and PC's, and the study said that the papilla and the matrix region had been removed under an experiment, and it said that the papilla and matrix still regrew because their stem cells existed within the bulge. So it seems that the problem is directly linked to the number of existent PC's.

It seems that two factors are present here: 1) chronic inflammation causes continued tissue degeneration 2) poor blood circulation may result in poor migration of PC's within the bulge. When there aren't enough PC's reaching the bulge, then this might result in poor wound healing, or rather poor healing of the matrix region.

And on a final note: perhaps the hairline area is harder to treat with minox because this is the area which we have pressed against a pillow for the entire 8 hours we are asleep, so the compressed capillary network might further hinder PC migration. The expanded skull might also play a role too.

Apologies for wild-goose-chase of a post.