I'm looking for a crazy study....

[docj077]

...that would be most beneficial to my hair loss research. However, I'm unable to find anything on any website that could possibly help me.

So, here's my dilemma...

Granted, my knowledge of science isn't at the genius level, but I think I have some of this hair loss moleucular biology down.

In susceptible individuals, DHT binds the androgen receptor on the dermal papillae, which causes the release of secondary mediators that affect keratinocytes. Molecules like TGF-beta are such molecules and cause the hair follicle to enter catagen with a corresponding shortening of anagen. TGF-beta also apparently causes cells in the matrix around the hair follicle to produce collagen and there is even a good chance that a mild immune response occurs causing perifollicular fibrosis.

That's how I understand it, but I'm always open to suggestions.

So, now what I'm trying to figure out is the genetic link to how the body can even allow this process. I know that triplet repeat mutations have been observed in the androgen receptor gene present on the X chromosome. I also know that the androgen receptor/androgen complex enters the cell nucleus of the cell that the androgen binds to and causes downstream effects. At least in vitro, those effects seem to be increased TGF-beta RNA production. In vivo, TGF-beta accumulation can be seen around follicles.

The study that I'm really looking for is the one that clearly shows that the androgen receptor/androgen complex not only causes the transcription of the TGF-beta gene, or a gene with a protein product that increases TGF-beta, but also shows that this link between the androgen receptor complex and TGF-beta gene transcription only happens in men with hair loss. I also need to see a study that shows that their is no link between the two in men without male pattern baldness.

From what I know, TGF-beta actually protects the hair follicle by causing it to enter catagen when there is damage done to the follicle itself. This process seems to be increased and inappropriate in men with hair loss. What I don't know is whether all men have androgen receptors on their hair follicles. If they do, then evolution or some other process has linked the binding of androgens to the production of TGF-beta and I'd like to know why.

So, if anyone is aware of any studies that show any of the items that I'm looking for above, please let me know.

I think that science is getting closer by finally realizing that this is an immune system problem with defects in molecular mediators that are involved in the immune response. They've demonstrated their understanding by doing clinical trials with antibiotics and by showing that minoxidil's action is to prevent apoptosis by opening Kir 6.0 channels in mitochondria, which prevents the action of TGF-beta in susceptible cells. Minoxidil also effects this channel in smooth muscle cells causing dilation and increased blood flow to the hair follicle.

Any help is appreciated. Any opinions are most welcome.

 

[Bryan]

So, now what I'm trying to figure out is the genetic link to how the body can even allow this process. I know that triplet repeat mutations have been observed in the androgen receptor gene present on the X chromosome.

Well, perhaps more to the point is the fact that certain of those androgen receptor polymorphisms are strongly correlated with the incidence of male pattern baldness. That bothers me a little bit, because it implies that the DEGREE of androgenic stimulation is what determines whether or not you have balding. It's always been my little pet theory that not only is the degree important, but also the qualititave RESPONSE to androgens (as in body hair versus scalp hair). I still maintain that both are factors, despite the recent studies on androgen receptor polymorphisms in balding.

The study that I'm really looking for is the one that clearly shows that the androgen receptor/androgen complex not only causes the transcription of the TGF-beta gene, or a gene with a protein product that increases TGF-beta, but also shows that this link between the androgen receptor complex and TGF-beta gene transcription only happens in men with hair loss. I also need to see a study that shows that their is no link between the two in men without male pattern baldness.

Do you want those studies because there's still a certain amount of doubt in your mind about the androgen/TGF-beta link? You're still not fully convinced by that in vitro study?

BTW, I'm a little bothered by your last sentence about wanting to see a study proving that "there is no link between the two in men without male pattern baldness". I think it's quite possible that it's not as black-and-white as that. Judging by that damned androgen receptor polymorphism study, I think it's quite conceivable that there's a link between the two in men with male pattern baldness _and_ in men without male pattern baldness, but it's just a matter of degree. In other words, maybe androgens stimulate more TGF-beta in balding men than they do in non-balding men.

What I don't know is whether all men have androgen receptors on their hair follicles.

ALL human scalp hair follicles contain androgen receptors, according to Whiting. If I had a dollar for every time I've mentioned that on hairloss sites, I could go ahead and retire right now! :wink:

If they do, then evolution or some other process has linked the binding of androgens to the production of TGF-beta and I'd like to know why.

More specifically, we need to know why scalp hair follicles and body hair follicles respond in opposite ways to androgens (which almost certainly includes the TGF-beta response).

I think that science is getting closer by finally realizing that this is an immune system problem with defects in molecular mediators that are involved in the immune response.

Docj, I have not come across a single study in the medical literature which discussed or even acknowledged something which hairloss site posters like us have been discussing for years; namely, the alleged "attack" on hair follicles by the immune system in male pattern baldness. Dr. Proctor has been talking about that for years, but I've never seen anything in the published medical literature. Why do you suppose that is?

I want to emphasize here that there are studies having to do with inflammation in balding (discussing perifollicular lymphocyte infiltrates, etc.), but they don't actually hint or imply that the immune system is attacking the hair follicle. A lengthy and highly technical study I have right here suggests that androgens stimulate sebum production, which feeds the growth of microorganisms, which in turn attracts the attention of the immune system. But not a word about the hair follicles themselves possibly being the objects of interest to the immune system. What do you think about all that?

They've demonstrated their understanding by doing clinical trials with antibiotics and by showing that minoxidil's action is to prevent apoptosis by opening Kir 6.0 channels in mitochondria, which prevents the action of TGF-beta in susceptible cells. Minoxidil also effects this channel in smooth muscle cells causing dilation and increased blood flow to the hair follicle.

So why do you suppose that some other vasodilators (ones that aren't in the same chemical class as minoxidil, diazoxide, etc.) don't affect hair growth (that's always been the traditional response to anyone suggesting such an explanation for minoxidil's effect on hair)?

Bryan

 

[docj077]

Bryan,

You have a lot of information there and you've dealt with a lot of my questions.

I really have no doubt that there is an androgen/TGF-beta link, as you say. I also understand that there are different androgen receptor polymorphisms with the degree of change being directly correlated with the severity of hair loss in susceptible men. I can definitely see it as a spectrum-type disorder with high susceptible men on one end with a certain androgen receptor mutation and men with no problem at all on the other end with no mutation at all. I'm just very curious to know if these men with no mutation have their androgen response unlinked from the TGF-beta pathway, so they are protected in two ways. No androgen stimulation and no downstream effects of these androgens. That's really what I'm trying to figure out. I have no doubt in my mind that the two are linked in men with male pattern baldness and that the androgen receptor is mutated.

As for the Minoxidil, the point I was trying to make is that Minoxidil is mostly an anti-apoptotic compound as it's vasodilatory capabilities are mentioned far too much in hair loss communities. Although it works through a different mechanism, the end result with minoxidil is to prevent TGF-beta induced apoptosis, which is pretty much the same way a lot of the herbs work that we've been discussing around here.

Personally, I think that there is too much emphasis on increasing blood flow to the scalp in some people. I really believe that this causes irritation and only furthers the progression of hair loss since it causes TGF-beta to send the hair follicle into dormancy. So, these people that use hair products that irritate their scalp and cause a mild immune response may rejoice, because it looks like blood is getting to their scalp, but they are actually worsening both the cause of hair loss and their potential outcome. They have androgen-induced TGF-beta production and damage-induced TGF-beta production. They put themselves in a catch 22 at that point.

As for your statement about what causes facial hair growth vs. what causes scalp hair growth, that's a tough question. I get in trouble for mentioning things this way, but facial hair growth is induced by androgen-induced release of IGF-1. IGF-1 is a hair growth stimulator. This same molecule is seen in vivo in people taking propecia and actually directly correlates with their response to the drug. The higher your IGF-1, the better your outcome. If this molecule could be used for hair loss, we'd all be better off, but high doses of the stuff causes massive shedding, which is probably the same reason why people on finasteride experience sheds. It's merely due to increased IGF-1. Don't quote me on that last part as it's just a theory.

What needs to happen is science must understand what sort of difference there is in the androgen receptor in the scalp vs. the receptor in the face. Then, science needs to figure out why TGF-beta production is increased in the scalp while IGF-1 is elevated in facial hair and other areas. I wish I knew whether the TGF-beta gene is simply missing in these areas or if the receptor targets the IGF-1 gene instead. I want to know if a mutation has linked TGF-beta production to androgen receptor binding instead of linking IGF-1 production to the same phenomenon.

Also, sorry about the immune response thing. I've seen studies linking fibrosing alopecia to lymphocytic infiltrates around the hair follicle. I've never seen a histological slide demonstrating the same thing in men with androgenic alopecia.

 

[michael barry]

Bryan wrote:
"Docj, I have not come across a single study in the medical literature which discussed or even acknowledged something which hairloss site posters like us have been discussing for years; namely, the alleged "attack" on hair follicles by the immune system in male pattern baldness. Dr. Proctor has been talking about that for years, but I've never seen anything in the published medical literature. Why do you suppose that is?

I want to emphasize here that there are studies having to do with inflammation in balding (discussing perifollicular lymphocyte infiltrates, etc.), but they don't actually hint or imply that the immune system is attacking the hair follicle.

Bryan,
I wonder what the medical estabishment thinks about that immuno-deficient mouse study that saw human male pattern baldness vellus hairs transplanted to human skin on the mice's backs regenerate as well at 22 weeks with non-male pattern baldness hair from the same donors? Or what they think about Cyclosporin's effect internally on hair growth?

Have no medical journals even discussed this in print to your knowledge?




Bryan,
You metioned "A lengthy and highly technical study I have right here suggests that androgens stimulate sebum production, which feeds the growth of microorganisms, which in turn attracts the attention of the immune system. But not a word about the hair follicles themselves possibly being the objects of interest to the immune system. What do you think about all that? "

Isn't that asotonishing to you? I mean if we KNOW that men born without 5AR2 dont go bald, and 5AR1 is associated with the sebaceous gland, how COULD they come up with that conclusion. I mean finasteride alone never lessened the oiliness of my scalp. Dutasteride (I piddled with that for a few months just to see its effect) did somewhat. Green tea extract has lessened the oiliness some. Revivogen, despite being oily itself, sees me have less oil at the end of the day up there if I wash it out in the morning. Everybody knows about ketoconazale cutting sebum levels somewhat.

I mean really Bryan, Im suprised that any medical journal would think micro organisms in sebum would elicit an immune attack when all you have to do is drive downtown to see street alcoholics who dont bathe twice a year, with visibly greasy, filthy hair...................have full heads of hair. If that were so, all the cowboys in the old west would have been bald because they couldnt often bathe, wore cowboy hats that plastered their sebum-rich hair to their scalps, and no doubt wiped their sweaty foreheads several times a day. Tom Hagerty believes the oleic acid in sebum should counteract the fact that there are +some+ DHT molecules therein.

I dont know what Docj thinks about this, but Im very suprised that is their conclusion. I dont pretend to have the answers to baldness, but I'd lose alot of money if I were a betting man and this idea was right. Transplants dont get bothered by sebum secretions sure enough (often to the patients despair as the native hair falls out around them 20 years later).


One other note that you, Bryan, might find humorous. I seen some downloadable Comcast video of a story concerning a stingray attack in Florida. One of the trauma unit docs had one of the most profound combovers IVE EVER SEEN. Here, an eductated man, pulling hair from back BEHIND his ears to cover frontal baldness. He looked like it may have been permed also. Awful. Docj, guys like YOU and Bryan, are why I always was confident baldness would someday be "solved" because docs and science-minded guys also go bald. I figured one or two of the right guys would research the hell out of it in their spare time and "solve it" once and for all. Now Im just pulling for Intercytex pulling off a cloning protocol mostly.

 

[CCS]

So could too much dutasteride make too much IGF-1? Could different parts of the scalp, say front and back, have different optimal IGF-1 doses?

 

[docj077]

So could too much dutasteride make too much IGF-1? Could different parts of the scalp, say front and back, have different optimal IGF-1 doses?

I really want to know the answers to the above questions, as well. I want to know if taking propecia or avodart actually steadily increases IGF-1 production until it reaches a critical point, which sends the hair follicle into a shedding phase and resets the system so that IGF-1 has to accumulate again before the next shed can take place with normal growth taking place as the hair cycles and IGF-1 increases.

As for these drugs having a different effect on the front vs. the back, I have no good reasoning for that phenomenon. I really wish I knew, because it would be nice to find out this information for people who continue to recede while taking these drugs. It's a very real possibility that 5AR type II inhibitors do somehow increase testosterone in the sebaceous glands leading to increased DHT and sebum production. However, I think people have posted studies that show this doesn't happen. I wish they did, because if increased sebum and a corresponding inflammation due to these drugs was the problem, then we could help people that end up with a receding hairline by simply telling them to shampoo more often. However, this wouldn't explain why recession happens with people on avodart as it should decrease sebum production all together and I'm not sure if increased testosterone in the scalp is proven or if it's even linked to hair loss.

There's something else we're missing. Some molecule that is increased or decreased when people take 5AR type II inhibitors besides DHT, TGF-beta, or IGF-1 and I really want to know what it is. The other option is that the frontal hairline is simply more susceptible to the effects of IGF-1 and simply becomes so overproliferative that the cells within the hair follicle undergo apoptosis anyway as a protective measure.

I really don't know.

 

[CCS]

Does that mean IGT-1 caused catagen just means rapid cycling, and not progressive loss?

 

[Bryan]

I really have no doubt that there is an androgen/TGF-beta link, as you say. I also understand that there are different androgen receptor polymorphisms with the degree of change being directly correlated with the severity of hair loss in susceptible men. I can definitely see it as a spectrum-type disorder with high susceptible men on one end with a certain androgen receptor mutation and men with no problem at all on the other end with no mutation at all. I'm just very curious to know if these men with no mutation have their androgen response unlinked from the TGF-beta pathway, so they are protected in two ways. No androgen stimulation and no downstream effects of these androgens. That's really what I'm trying to figure out.

I see no a priori reason to think or even suspect that there's some connection between having or not having the mutated androgen receptor gene, and having or not having their androgen response unlinked from the TGF-beta pathway. Until I see evidence to the contrary, I'll assume that the presence or absence of those AR mutations is simply a factor in the degree of androgenic stimulation, and that the cellular response to those androgens is a separate issue.

As for your statement about what causes facial hair growth vs. what causes scalp hair growth, that's a tough question. I get in trouble for mentioning things this way, but facial hair growth is induced by androgen-induced release of IGF-1. IGF-1 is a hair growth stimulator. This same molecule is seen in vivo in people taking propecia and actually directly correlates with their response to the drug. The higher your IGF-1, the better your outcome.

I'm interested only rather indirectly in the specific substances which stimulate hairgrowth (and suppress it, for that matter). One can imagine cataloguing a veritable "alphabet soup" of various substances (TGF-beta and IGF-1 I'm sure are not the only ones) that have an effect on hair follicles, with stimulants on one side and suppressants on the other side! Again, the most pressing concern is to finally get to the bottom of why androgens produce those substances in an opposite fashion in scalp hair follicles versus body hair follicles. Of course, I fully acknowledge that identifying all those growth factors and growth inhibitors in the first place will probably be a prerequisite for that.

What needs to happen is science must understand what sort of difference there is in the androgen receptor in the scalp vs. the receptor in the face.

I don't think there IS any difference. At least, if I were a betting man, I'd bet my whole bankroll on it. I think the difference between scalp hair follicles and body hair follicles (in the same individual, of course) lies entirely in the RESPONSE to androgens in the target cells. A stimulation of one kind of follicle and a suppression of the other kind of follicle by androgens can't be explained merely by the degree of androgenic stimulation. At least, I can't think of any reasonable, non-ad hoc (non-Foote-esque) explanation for it!

Then, science needs to figure out why TGF-beta production is increased in the scalp while IGF-1 is elevated in facial hair and other areas. I wish I knew whether the TGF-beta gene is simply missing in these areas or if the receptor targets the IGF-1 gene instead. I want to know if a mutation has linked TGF-beta production to androgen receptor binding instead of linking IGF-1 production to the same phenomenon.

Indeed. They need to trace all the steps in the molecular pathways. It's not gonna be easy.

Bryan

 

[Bryan]

Bryan,
I wonder what the medical estabishment thinks about that immuno-deficient mouse study that saw human male pattern baldness vellus hairs transplanted to human skin on the mice's backs regenerate as well at 22 weeks with non-male pattern baldness hair from the same donors? Or what they think about Cyclosporin's effect internally on hair growth?

Have no medical journals even discussed this in print to your knowledge?

Not to my knowledge. That mouse study was fairly recent, and as I've told Stephen Foote more than once, it hasn't been duplicated by anyone else yet. Let's give them some more time, and see what all those other docs and scientists think about it.

BTW, I think even Dr. Proctor ascribes cyclosporin's (alleged) beneficial effect on male pattern baldness to something other than it's effect on the immune system.

Bryan,
You metioned "A lengthy and highly technical study I have right here suggests that androgens stimulate sebum production, which feeds the growth of microorganisms, which in turn attracts the attention of the immune system. But not a word about the hair follicles themselves possibly being the objects of interest to the immune system. What do you think about all that? "

Isn't that asotonishing to you? I mean if we KNOW that men born without 5AR2 dont go bald, and 5AR1 is associated with the sebaceous gland, how COULD they come up with that conclusion. I mean finasteride alone never lessened the oiliness of my scalp. Dutasteride (I piddled with that for a few months just to see its effect) did somewhat. Green tea extract has lessened the oiliness some. Revivogen, despite being oily itself, sees me have less oil at the end of the day up there if I wash it out in the morning. Everybody knows about ketoconazale cutting sebum levels somewhat.

Michael, I really don't understand what it is you find astonishing. Neither am I sure what "conclusion" it is you think they're coming up with.

I mean really Bryan, Im suprised that any medical journal would think micro organisms in sebum would elicit an immune attack when all you have to do is drive downtown to see street alcoholics who dont bathe twice a year, with visibly greasy, filthy hair...................have full heads of hair. If that were so, all the cowboys in the old west would have been bald because they couldnt often bathe, wore cowboy hats that plastered their sebum-rich hair to their scalps, and no doubt wiped their sweaty foreheads several times a day.

I think you're missing the point, which is that the study doesn't seem to be BLAMING that immune response for hairloss. They seem to be just trying to explain WHY the immune response is there, which is (apparently according to their way of thinking) only rather indirectly associated with male pattern baldness.

Bryan

 

[Old Baldy]

Bryan and Doctor: I always thought fibrosis was a key indicator that the immune system is involved in male pattern baldness? You know, the "inflammation/immune system response" opined by some doctors.

I know some doctors feel fibrosis is an "after effect" (i.e., the follicle has already shrunk and there is no need for blood vessels, etc.).

However, isn't any type of fibrosis an indication that the immune system is "neutralizing" something? Well, maybe this is too broad a question so I'll ask the following:

What system(s) of ours creates scarring?

Perifollicular fibrosis: pathogenetic role in androgenetic alopecia.Yoo HG, Kim JS, Lee SR, Pyo HK, Moon HI, Lee JH, Kwon OS, Chung JH, Kim KH, Eun HC, Cho KH.
Department of Dermatology, Seoul National University College of Medicine, Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, and Institute of Dermatological Science, Seoul National University.

Androgenetic alopecia (Androgenetic Alopecia) is a dihydrotestosterone (DHT)-mediated process, characterized by continuous miniaturization of androgen reactive hair follicles and accompanied by perifollicular fibrosis of follicular units in histological examination. Testosterone (T: 10(-9)-10(-7) M) treatment increased the expression of type I procollagen at mRNA and protein level. Pretreatment of finasteride (10 [-8]) M) inhibited the T-induced type I procollagen expression at mRNA (40.2%) and protein levels (24.9%). T treatment increased the expression of transforming growth factor-beta 1 (TGF-beta1) at protein levels by 81.9% in the human scalp dermal fibroblasts (DFs). Pretreatment of finasteride decreased the expression of TGF-beta1 protein induced by an average of T (30.4%). The type I procollagen expression after pretreatment of neutralizing TGF-beta1 antibody (10 mug/ml) was inhibited by an average of 54.3%. Our findings suggest that T-induced TGF-beta1 and type I procollagen expression may contribute to the development of perifollicular fibrosis in the Androgenetic Alopecia, and the inhibitory effects on T-induced procollagen and TGF-beta1 expression may explain another possible mechanism how finasteride works in Androgenetic Alopecia.

PMID: 16755026 [PubMed - in process]

Now, what system of ours causes the above responses discussed by the researchers? Being a layman, it is difficult for me to sort these things out.

Isn't Lupus a classic type of disease where the immune system causes fibrosis? There are others but this is why I always thought fibrosis had a strong immune system component?

What part does the immune system play in the following article?

Inflammation in androgenetic alopecia

Years of research have led to the conclusion that androgenetic alopecia may be a result of an alteration in the hair growth cycle and/or a premature aging of the pilosebaceous unit. The etiology of androgenetic alopecia has been defined as multifactorial or even polygenic in nature. The fact that the success rate of treatment with either antihypertensive agents or modulators of androgen metabolism barely exceeds 30 percent, has led to some researchers to propose the possibility of other pathways that mediate this form of hair loss.

Hair follicle inflammation in androgenetic alopecia

The new focus, therefore, is the implication of various activators of inflammation in the etiology of androgenetic alopecia. An early study referred to an inflammatory infiltrate of mononuclear cells and lymphocytes in about 50 percent of the scalp samples observed. Jaworsky et al. subsequently in 1992 referred to an inflammatory infiltrate of activated T cells and macrophages in the upper third of the hair follicles, associated with an enlargement of the follicular dermal-sheath composed of collagen bundles (perifollicular fibrosis), in regions of actively progressing alopecia. Whiting has documented that horizontal sections of scalp biopsies indicated that the perifollicular fibrosis is generally mild, consisting of loose, concentric layers of collagen (a fibrous protein that makes up connective tissue) that must be distinguished from cicatricial alopecia. Another study conducted on 412 patients (193men and 219 women) showed the presence of a significant degree of inflammation and fibrosis in at least 37 percent of androgenetic alopecia cases.

The location of the infiltrate near the infrainfundibulum clearly differentiates androgenetic alopecia from alopecia areata, which is characterized by infiltrates in the bulb and dermal papilla zone. The term ‘microinflammation’ was proposed by Mahe and colleagues because the process of inflammation in androgenetic alopecia adopts a slow, subtle, painless and lethargic course, in contrast to the inflammatory and destructive process that has been seen in the classical inflammatory scarring alopecias.

The significance of these findings has remained controversial. However, only 55 percent of male pattern androgenetic patients with microinflammation had hair re-growth in response to Minoxidil treatment, which was less than the 77 percent of patients with no signs of inflammation, suggesting that, to some extent, perifollicular microinflammation may account for some cases of male pattern androgenetic alopecia which do not respond to Minoxidil.

Inflammatory phenomena in pattern baldness

An important fact to be established is how the inflammatory reaction pattern in androgenetic alopecia is generated around the individual hair follicle. Inflammation is regarded as a multi-step process which and is assigned to a central major mediator or pathway. Mahe et al believe that the presence of a perifollicular infiltrate in the upper follicle near the infundibulum points to the fact that the primary causal event for the triggering of inflammation might occur near the infundibulum.

On the basis of this localization and the microbial colonization of the follicular infundibulum with Propionibacterium sp., Staphylococcus sp., Malassezia sp., or other members of the transient flora, some researchers speculate that that microbial toxins or antigens could be involved in the generation of the inflammatory response. The production of porphyrins (any of various organic compounds containing four pyrrole rings, occurring universally in protoplasm, and functioning as a metal-binding cofactor in hemoglobin) by Propionibacterium sp. in the pilosebaceous duct of 58 percent of androgenetic alopecia patients (compared with 12 percent of control subjects) has also been considered to be a possible cofactor of this initial pro-inflammatory stress.

Alternatively, keratinocytes themselves may respond to chemical stress from irritants, pollutants, and UV irradiation, by producing radical oxygen species and nitric oxide, and by releasing intracellularly stored IL-1a. This pro-inflammatory cytokine by itself has been shown to inhibit the growth of isolated hair follicles in culture. Skin keratinocytes, which may also have antigen-presenting capabilities, could theoretically induce T-cell (white blood cell) proliferation in response to bacterial antigens. These antigens, once they have been “taggedâ€, are then selectively destroyed by infiltrating macrophages (cells that act as scavengers within the body), Langerhans cells (dendritic cells in the skin that pick up an antigen and transport it to the lymph nodes), or natural killer cells (immune system cells that destroy foreign bodies or abnormal cells that are marked with antibodies).
When any of the causal agents described above persist, it leads to sustained inflammation of the hair follicle. This phase of inflammation often results in tissue remodeling, where collagenases (various enzymes that catalyze the hydrolysis of collagen and gelatin) may play an active role. Collagenases are suspected to contribute to the tissue changes and the so-called “perifollicular fibrosis†by “preparing†tissue matrix and basal membranes for macrophages and T-cell adhesion.

Relations between inflammation and steroidogenesis

It has been proven beyond doubt that androgens, in the form of testosterone or its metabolites, are the prerequisites for development of common male pattern baldness. According to Mahe, the only apparent link that can be established between androgen metabolism and the complex inflammatory process proposed by him is sebum production, which is controlled by androgens. As sebum harbors a large amount of microorganisms, which use lipids as nutrients, it is possible that, at least for some individuals, androgen metabolism might make possible the colonization of the sebaceous infundibulum and sebaceous ducts by microorganisms. These microorganisms may well be involved in the first steps of pilosebaceous unit inflammation.

Conclusion

Therefore Mahe and his team deduce that the genetic factors and androgen metabolism are only responsible for about 30 percent of the androgenetic alopecia cases, and factors which lead to the lethal damage by microinflammatory process include androgens, microbial flora, endogenous or exogenous stress, genetic imbalance, amongst others. Formation of fibrous tissue or fibroplasia of the dermal sheath, which surrounds the hair follicle, is now suspected to be a common terminal process resulting in the miniaturization. Involution of the pilosebaceous unit in this form of baldness and sustained microscopic follicular inflammation with connective tissue remodeling, eventually resulting in permanent hair loss, is considered a possible cofactor in the complex etiology of androgenetic alopecia. However, till date, the inflammatory component has not been explored in developing treatment protocols for androgenetic alopecia.

I don't know about the micro-organism stuff but the bold writing above is what I see alot when male pattern baldness is discussed by doctors.

 

[docj077]

Old Baldy,

Lupus does have a strong immune system component, but there is a difference here. In Lupus, a person develops antibodies against their own DNA and associated structures. These antibodies accumulate and form immune complexes or groups of antibodies. As they move through the systemic circulation, they become trapped in places like the kidneys, skin, lungs, etc. Once they become stationary, the complement system attaches to the antibodies and immune cells are attracted to the complexes with complement bound to them. Once immune cells (macrophages, lymphocytes, etc.) arrive at the site, they begin to attack any and all cells around the area of immune complex deposition.

male pattern baldness seems to be slightly different with no real evidence of immune complex deposition or even an autoimmune component. Under the microscope a person can see increased fibrosis and increased collagen deposition around the hair follicle. This is mostly a fibroblast mediated process caused by the release of TGF-beta (at least it seems that way according to the research). One might even see lymphocytic infiltrates if there is an inflammatory component.

One should not be so quick as to compare the two, because it's basically DHT putting a process into motion that causes the fibrosis and not an immune response.

If the immune system is involved, it's involved through simple molecular mediators that are considered to be part of an immune response. Fibrosis and collagen deposition seems to require TGF-beta and fibroblasts only. Hopefully, researchers will give us some more molecular options soon.

 

[Old Baldy]

I see, thank you.

Dr. Proctor has always said immune system cells surround male pattern baldness follicles in greater numbers than normal. What would cause this increased concentration? What type of message is the male pattern baldness follicle sending that would result in unreasonable accumulations of immune system cells?

Dr. Proctor says it's almost as if the immune system is rejecting the male pattern baldness follicle. I guess we don't know what part of the DHT "cascade of events" is causing this reaction either?

 

[docj077]

I see, thank you.

Dr. Proctor has always said immune system cells surround male pattern baldness follicles in greater numbers than normal. What would cause this increased concentration? What type of message is the male pattern baldness follicle sending that would result in unreasonable accumulations of immune system cells?

Dr. Proctor says it's almost as if the immune system is rejecting the male pattern baldness follicle.

You know, I've heard the immune system cell accumulation theory go both ways. Some say there clearly is an increase and others see nothing. I don't know if it depends on the person or their degree of hair loss...it's rather confusing.

I'll have to do some thinking and some research on this one.

 

[Old Baldy]

You know, maybe it does depend on the person. The article I posted above suggests that might be why some people respond differently to finasteride., etc.

Not to mention that a veteran posted a study a while back where a certain DNA "combination" made it impossible for a person to metabolize finasteride. properly. Some people have that genetic makeup and others do not. I can't remember the technical specifics of that study but you get the point.

 

[S Foote.]

Old Baldy,

Lupus does have a strong immune system component, but there is a difference here. In Lupus, a person develops antibodies against their own DNA and associated structures. These antibodies accumulate and form immune complexes or groups of antibodies. As they move through the systemic circulation, they become trapped in places like the kidneys, skin, lungs, etc. Once they become stationary, the complement system attaches to the antibodies and immune cells are attracted to the complexes with complement bound to them. Once immune cells (macrophages, lymphocytes, etc.) arrive at the site, they begin to attack any and all cells around the area of immune complex deposition.

male pattern baldness seems to be slightly different with no real evidence of immune complex deposition or even an autoimmune component. Under the microscope a person can see increased fibrosis and increased collagen deposition around the hair follicle. This is mostly a fibroblast mediated process caused by the release of TGF-beta (at least it seems that way according to the research). One might even see lymphocytic infiltrates if there is an inflammatory component.

One should not be so quick as to compare the two, because it's basically DHT putting a process into motion that causes the fibrosis and not an immune response.

If the immune system is involved, it's involved through simple molecular mediators that are considered to be part of an immune response. Fibrosis and collagen deposition seems to require TGF-beta and fibroblasts only. Hopefully, researchers will give us some more molecular options soon.

"Inflammatory Manifestations of Experimental Lymphatic Insufficiency."


http://www.ncbi.nlm.nih.gov/entrez/quer ... s=16834456

Quote:


"The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response."

Whilst there is no proof at all of any direct pathway for DHT mediated immunology in male pattern baldness, there is proof of these conditions in lymphedema.

S Foote.

 

[S Foote.]

I don't think there IS any difference. At least, if I were a betting man, I'd bet my whole bankroll on it. I think the difference between scalp hair follicles and body hair follicles (in the same individual, of course) lies entirely in the RESPONSE to androgens in the target cells. A stimulation of one kind of follicle and a suppression of the other kind of follicle by androgens can't be explained merely by the degree of androgenic stimulation. At least, I can't think of any reasonable, non-ad hoc (non-Foote-esque) explanation for it!

Bryan you are a complete fraud :roll:

You are the master of unproven, unprecedented speculation on these forums!

Your blatent contraditions in your past posts have been pointed out to people before. Do you really want me to embarrass you with them again?

Because if you keep on taking these cheap unqualified and unjustified digs at me, i will 8)

S Foote.

 

[docj077]

Old Baldy,

Lupus does have a strong immune system component, but there is a difference here. In Lupus, a person develops antibodies against their own DNA and associated structures. These antibodies accumulate and form immune complexes or groups of antibodies. As they move through the systemic circulation, they become trapped in places like the kidneys, skin, lungs, etc. Once they become stationary, the complement system attaches to the antibodies and immune cells are attracted to the complexes with complement bound to them. Once immune cells (macrophages, lymphocytes, etc.) arrive at the site, they begin to attack any and all cells around the area of immune complex deposition.

male pattern baldness seems to be slightly different with no real evidence of immune complex deposition or even an autoimmune component. Under the microscope a person can see increased fibrosis and increased collagen deposition around the hair follicle. This is mostly a fibroblast mediated process caused by the release of TGF-beta (at least it seems that way according to the research). One might even see lymphocytic infiltrates if there is an inflammatory component.

One should not be so quick as to compare the two, because it's basically DHT putting a process into motion that causes the fibrosis and not an immune response.

If the immune system is involved, it's involved through simple molecular mediators that are considered to be part of an immune response. Fibrosis and collagen deposition seems to require TGF-beta and fibroblasts only. Hopefully, researchers will give us some more molecular options soon.

"Inflammatory Manifestations of Experimental Lymphatic Insufficiency."


http://www.ncbi.nlm.nih.gov/entrez/quer ... s=16834456

Quote:


"The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response."

Whilst there is no proof at all of any direct pathway for DHT mediated immunology in male pattern baldness, there is proof of these conditions in lymphedema.

S Foote.

There is no proof of edema in hair loss, either. The only hair loss related condition that clearly demonstrates edema is lipedematous alopecia and the histological profile of that disease is different from androgenic alopecia as there is edema, but there is also degeneration of the subcutaneous adipose tissue.

Also, there is no proof of lymphedema in hair loss. If you have the study and the slide demonstrating clear lymphedema in a group of males with androgenic alopeica, please post it. Please post the study along with the histological stains used, the markers used to prove that androgen receptors exist on the lymph vessels/striated muscle, or proof that striated muscle hypertrophy clearly causes lymphedema in the scalp. Once you've proven that muscle hypertrophy is caused by androgen binding, prove that lymphedema is the result of the hypertrophy when the lymphatic vessels are in the subcutaneous tissue and the muscles themselves exist in much deeper tissue. Please prove it with both a histological section and a clearly dissected human specimen or anatomy atlas diagram.

Please post the study that demonstrates that the majority of hair loss sufferers have pitting edema of the scalp with the measured average size of the edema and fluid wave along with the other physical findings that demonstrate that the edema is the absolute cause of hair loss. One you've proven that, please post a link to the study that clearly shows that the perifollicular fibrosis seen in patients with androgenic alopecia is secondary to this lymphedema and also answer why there isn't a general immune system response in all male pattern baldness cases when such edema is present.

Then, once you're done with that, please enlighten all of us as to why men who are castrated do not regrow all the hair that they've lost due to DHT. It's pretty clear that muscle hypertrophy requires a constant source of androgen and yet these men stay bald. So, what keeps the lymphedema a constant in these men? Why don't they simply regrow all their hair if there is no longer a DHT mediated hypertrophy and subseqent lymphedema?

One more thing, please identify why men or women who go on diuretics for various causes fail to remove the edema from their scalp (they have to according to your theory) and yet they remove the edema from everywhere else in their bodies, which would only serve to prove your point that lymphedema causes hair loss. Explain why the removal of all edema doesn't cause hair regrowth in these patients.

Lastly, prove that minoxidil removes edema from the scalp and doesn't act by inhibiting the Kir 6.0 channel preventing TGF-beta induced apoptosis of cells within the hair follicle. Prove that pitting edema is reduced in patients taking minoxidil and then explain the nature of the edema that results in other parts of the body secondary to vessel dilation and increased edema. Why does this edema happen in the limbs and yet the complete opposite happens in the scalp?

If you fail to answer or discuss all these questions, then please do not post in this thread again. Simply attacking others will no longer be viewed as acceptable.

If you can't be a scientist, then learn to be a human being.

 

[S Foote.]

Old Baldy,

Lupus does have a strong immune system component, but there is a difference here. In Lupus, a person develops antibodies against their own DNA and associated structures. These antibodies accumulate and form immune complexes or groups of antibodies. As they move through the systemic circulation, they become trapped in places like the kidneys, skin, lungs, etc. Once they become stationary, the complement system attaches to the antibodies and immune cells are attracted to the complexes with complement bound to them. Once immune cells (macrophages, lymphocytes, etc.) arrive at the site, they begin to attack any and all cells around the area of immune complex deposition.

male pattern baldness seems to be slightly different with no real evidence of immune complex deposition or even an autoimmune component. Under the microscope a person can see increased fibrosis and increased collagen deposition around the hair follicle. This is mostly a fibroblast mediated process caused by the release of TGF-beta (at least it seems that way according to the research). One might even see lymphocytic infiltrates if there is an inflammatory component.

One should not be so quick as to compare the two, because it's basically DHT putting a process into motion that causes the fibrosis and not an immune response.

If the immune system is involved, it's involved through simple molecular mediators that are considered to be part of an immune response. Fibrosis and collagen deposition seems to require TGF-beta and fibroblasts only. Hopefully, researchers will give us some more molecular options soon.

"Inflammatory Manifestations of Experimental Lymphatic Insufficiency."


http://www.ncbi.nlm.nih.gov/entrez/quer ... s=16834456

Quote:


"The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response."

Whilst there is no proof at all of any direct pathway for DHT mediated immunology in male pattern baldness, there is proof of these conditions in lymphedema.

S Foote.

There is no proof of edema in hair loss, either. The only hair loss related condition that clearly demonstrates edema is lipedematous alopecia and the histological profile of that disease is different from androgenic alopecia as there is edema, but there is also degeneration of the subcutaneous adipose tissue.

Also, there is no proof of lymphedema in hair loss. If you have the study and the slide demonstrating clear lymphedema in a group of males with androgenic alopeica, please post it. Please post the study along with the histological stains used, the markers used to prove that androgen receptors exist on the lymph vessels/striated muscle, or proof that striated muscle hypertrophy clearly causes lymphedema in the scalp. Once you've proven that muscle hypertrophy is caused by androgen binding, prove that lymphedema is the result of the hypertrophy when the lymphatic vessels are in the subcutaneous tissue and the muscles themselves exist in much deeper tissue. Please prove it with both a histological section and a clearly dissected human specimen or anatomy atlas diagram.

Please post the study that demonstrates that the majority of hair loss sufferers have pitting edema of the scalp with the measured average size of the edema and fluid wave along with the other physical findings that demonstrate that the edema is the absolute cause of hair loss. One you've proven that, please post a link to the study that clearly shows that the perifollicular fibrosis seen in patients with androgenic alopecia is secondary to this lymphedema and also answer why there isn't a general immune system response in all male pattern baldness cases when such edema is present.

Then, once you're done with that, please enlighten all of us as to why men who are castrated do not regrow all the hair that they've lost due to DHT. It's pretty clear that muscle hypertrophy requires a constant source of androgen and yet these men stay bald. So, what keeps the lymphedema a constant in these men? Why don't they simply regrow all their hair if there is no longer a DHT mediated hypertrophy and subseqent lymphedema?

One more thing, please identify why men or women who go on diuretics for various causes fail to remove the edema from their scalp (they have to according to your theory) and yet they remove the edema from everywhere else in their bodies, which would only serve to prove your point that lymphedema causes hair loss. Explain why the removal of all edema doesn't cause hair regrowth in these patients.

Lastly, prove that minoxidil removes edema from the scalp and doesn't act by inhibiting the Kir 6.0 channel preventing TGF-beta induced apoptosis of cells within the hair follicle. Prove that pitting edema is reduced in patients taking minoxidil and then explain the nature of the edema that results in other parts of the body secondary to vessel dilation and increased edema. Why does this edema happen in the limbs and yet the complete opposite happens in the scalp?

If you fail to answer or discuss all these questions, then please do not post in this thread again. Simply attacking others will no longer be viewed as acceptable.

If you can't be a scientist, then learn to be a human being.

Your stupidity is now clear for all to see "Doctor".

You started this thread in a quest for information you were looking for to support your idea's as all can see.

So it is clear you cannot at this time support your own opinions with any hard scientific evidence?

Your complete faliure as a scientist is confirmed when you "DEMAND" like Bryan, that "I" have to prove right down to the last detail my own opinions "right now"! :freaked: !

I have already provided for all to see, the hard evidence for my own opinions. :wink:

The big problem you and all the other psuedo scientists like Bryan have, is that you are incapable of putting together a body of scientific evidence according to the scientific rules!

All you do on these forums is make unjustified claims about particular information, with no consideration for the whole body of evidence.

I can provide a complete "body" of evidence to support my opinions.

You now come here asking for studies to try to support your previous rants about facts you just don't understand!

The studies you want just don't exist, because you are "wrong", end of story! :roll:

There are studies that refute your rantings, but as a psuedo scientist you choose to ignore these as psuedo scientists do. :roll:

I have always tried to give people the benefit of the doubt on these forums, but you are clearly a dangerous fool, sorry. :wink:

S Foote.

 

[docj077]

Your stupidity is now clear for all to see "Doctor".

You started this thread in a quest for information you were looking for to support your idea's as all can see.

So it is clear you cannot at this time support your own opinions with any hard scientific evidence?

Your complete faliure as a scientist is confirmed when you "DEMAND" like Bryan, that "I" have to prove right down to the last detail my own opinions "right now"! :freaked: !

I have already provided for all to see, the hard evidence for my own opinions. :wink:

The big problem you and all the other psuedo scientists like Bryan have, is that you are incapable of putting together a body of scientific evidence according to the scientific rules!

All you do on these forums is make unjustified claims about particular information, with no consideration for the whole body of evidence.

I can provide a complete "body" of evidence to support my opinions.

You now come here asking for studies to try to support your previous rants about facts you just don't understand!

The studies you want just don't exist, because you are "wrong", end of story! :roll:

There are studies that refute your rantings, but as a psuedo scientist you choose to ignore these as psuedo scientists do. :roll:

I have always tried to give people the benefit of the doubt on these forums, but you are clearly a dangerous fool, sorry. :wink:

S Foote.

*waits for Foote to post something meaningful*

*notices Foote didn't post anything meaningful*

*Leaves the thread in the same way Foote leaves his wife or girlfriend...unsatisfied* :freaked2:

Again, I'll be waiting for you to post your proof. You keep letting me down. Don't do that.

People in this thread are talking about one side of hair loss involving what I discussed earlier. Not the "crazy Foote school of lymphadenopathy and biological nonsense" side of hair loss. You have no human in vivo studies that demonstrate your theory at the molecular, histological, and physical levels.

Please do not post here again.

 

[S Foote.]

People in this thread are talking about one side of hair loss involving what I discussed earlier. Not the "crazy Foote school of lymphadenopathy and biological nonsense" side of hair loss. You have no human in vivo studies that demonstrate your theory at the molecular, histological, and physical levels.

Please do not post here again.

"Please do not post here again"!!!

Who put you in control of these forums?

That one statement in itself clearly shows you are deranged "Doctor" :roll:

I do have human in-vivo studies that demonstrate my theory. You on the other hand have "nothing" in-vivo to support your rantings, in fact the macaque in-vivo studies "prove" you wrong!

http://www.hairsite4.com/dc/dcboard.php ... ting_type=

Androgen driven follicle miniaturisation happens without any inflammation or fibrosis, that you claim is needed! Every decent hair loss scientist knows the immunology in humans is an associated, and not a "CAUSAL" factor!

So all your ridiculous speculation in this thread has no genuine basis "anyway" :roll: You are just wasting everyone's time.

The in-vivo studies that support my theory are these.

1/ This study clearly demonstrates that edema related to lymphatic insufficiency is linked to scalp follicle miniaturisation.

http://alopecia.researchtoday.net/archive/1/2/66.htm

Quote:

"The presence of ectatic lymphatic vessels in the two cases with hair loss was particularly emphasized."

2/ This study clearly demonstrates that lymphatic insufficiency can "ALSO" cause the kind of immunology we see in male pattern baldness.

http://www.ncbi.nlm.nih.gov/entrez/quer ... s=16834456

Quote:

" We found intense inflammatory changes in the dermis and the subdermis. The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response."

3/ This study clearly demonstrates through the sweating changes, that DHT "IS" increasing tissue fluid levels in the male pattern baldness scalp.

http://hairmillion.com/ref-hair-loss/ha ... 3.506.html

Put these "in-vivo" studies together, and it is clear that DHT is increasing fluid levels in male pattern baldness and that this causes "both" inflammation and follicle miniaturisation.

Even a moron like you "Doctor" should be able to see the clear "hard in-vivo" evidence for my theory 8)

S Foote.