Evidence That Cortisol Really Does Cause Hair Loss

[yerrag]

I could buy MCT oil just as well but I'll give the refined coconut oil a try first. On the ACV, I did some experimentation over a week applying something that is related to it - copper acetate (the acetate is how it's related). It didn't work, but I wonder now if it would have worked if I followed it up with the MCT (or functionally equivalent coconut oil derivative).

@tca300I tested the use of a 1:1 mixture of copper acetate and virgin coconut oil on my scalp last week. I think it worked. I still had some scales from previous, but no new scales seem to have formed. I let the mixture sit for an hour or two, then used a Dr. Woods tea tree castile soap to clean my hair afterwards. Since about a week has passed, I'm doing a repeat application, in the hope that any fungal remnants would be killed off. It would take a while to see the full effects, as in no more scales, and as in more hair.

 

[Travis]

I'm getting the impression that all causes converge on prostaglandins. For instance: The immune system's T cells release interferon-γ, which then goes to other cells to stimulate phospholipase A₂ mRNA transcription. Cyclosporine works by blocking interferon-γ. As far as I can tell, the only other cytokine that upregulates phospholipse A₂ is interleukin-1β . . . under the control of cortisol.

Most cytokines just activate phospholipase A₂, one time, but only two can increase the total number of phospholipase itself.

So hair loss appears to me—at the moment—to be a mixture of stress, linoleic acid, and food hidden allergy—basically anything that interrupts the natural prostaglandin hair growth signals of the transforming growth factor (TGF) system, which naturally controls the hair cycle through prostaglandin signalling (at a lower level.)

It's easy to explain the sex differential, but explaining the location is difficult. I think it ultimately would come down to the unique vascularization at that one particular area of the head. Androgens both increase both the size of the thymus and the adrenals, leading to more cortisol and T cells.

When applied directly to the hair follicle, DHT actually stimulates hair growth (believe it or not.)

 

[eddiem991]

I'm getting the impression that all causes converge on prostaglandins. For instance: The immune system's T cells release interferon-γ, which then goes to other cells to stimulate phospholipase A₂ mRNA transcription. Cyclosporine works by blocking interferon-γ. As far as I can tell, the only other cytokine that upregulates phospholipse A₂ is interleukin-1β . . . under the control of cortisol.

Most cytokines just activate phospholipase A₂, one time, but only two can increase the total number of phospholipase itself.

So hair loss appears to me—at the moment—to be a mixture of stress, linoleic acid, and food hidden allergy—basically anything that interrupts the natural prostaglandin hair growth signals of the transforming growth factor (TGF) system, which naturally controls the hair cycle through prostaglandin signalling (at a lower level.)

It's easy to explain the sex differential, but explaining the location is difficult. I think it ultimately would come down to the unique vascularization at that one particular area of the head. Androgens both increase both the size of the thymus and the adrenals, leading to more cortisol and T cells.

When applied directly to the hair follicle, DHT actually stimulates hair growth (believe it or not.)

First off, great post. How would you explain the diffrence between the sexes, is it estrogen?

 

[thisoldtown1978]

Hi guys, joining this discussion late. With regards to location - can we really discuss the pattern without mentioning the galea aponeurotica? My common sense is telling me that understanding this tissue as a functional piece of human anatomy is crucial.

 

[Travis]

First off, great post. How would you explain the diffrence between the sexes, is it estrogen?

I think it could be the thymus gland, mostly, but also perhaps the adrenals.

Hamilton made many observations in the '50s about androgens and hair loss. His arguments weren't biochemical; they were mostly epidemiological, and observational. When males are castrated young, they are largely protected from hair loss; however, castrating a male after the year 18 has little effect.

I read a few old studies on what happens to rats under these conditions. Early castration changes the entire adrenal output. The adrenals have androgen receptors, and they increase in size as a result of stimulation early in development. Androgens are always anabolic, and can never cause hair loss directly. Not even Phizer can't argue this point, as Finansteride® needs to be taken internally to have any effect at all. This way, they tacitly admit what I'm saying. Spironolactone works topically, and is more of a antimineralcorticoid than an antiandrogen.

Interferon-γ is produced nearly exclusively from T-cells, or cells derived from the thymus. Here, again, androgen acts anabolically to differentiate the thymus from the female phenotype. Males have a different immune parameters, something I had just found out yesterday. I haven't read, for example, studies such as the one listed below yet.

Giron-Gonzalez, J. A., et al. "Consistent production of a higher TH1: TH2 cytokine ratio by stimulated T cells in men compared with women." European journal of endocrinology (2000)​

I am willing to predict that you'd find higher amounts of interferon-γ in males. I consider this the public enemy №1 of cytokines, with interleukin-1β public enemy №2. Both these cytokines induce transcription of phospholipase A₂, and rats genetically-engineered to over-express this on the skin are bald just as you'd expect. Rats genetically-engineered to over-express interferon-γ are similarly bald, as are the ones over-expressing cyclooxygenase-2. Don't believe me? then do some GoogleScholararing: https://scholar.google.com

Louis Garza, when analyzing lipids (not cytokines or steroids) found that prostaglandin D₂ was synonymous with hair loss. I have just found that prostaglandin D₂ is a high-affinity ligand for the PPARα receptor, and also that this receptor has a promoter for interleukin-1β receptor (Table 2).

It might certainly seem that prostaglandins are highly involved. Perhaps hair loss can be perfectly understood, the confusion only coming from concentrating on only one correlation at once—not seeing the causality and interrelations. The most striking result from the interaction of interferon-γ and the cell is the transcription of phospholipase A₂; this happens to such an extent that you could consider this its primary function. This result from this event is, of course, a long release of prostaglandins from the cell membrane—longer than the transient stimulation from particles such as TGF-β₁.

I think someone needs to reanalyze the epidemiological correlations; perhaps plot alopecia against the linoleic acid consumption of populations. I wouldn't expect any hair loss to be observed among the coconut-eating islanders of the South Pacific, such as the ones studied by Ian Prior in his research on cardiovascular disease. I know he did a study on a migrants to New Zealand; and since he was studying cardiovascular disease, he would have kept track of the quantity and quality of lipids ingested and would have measured their blood concentrations.

Prior, Ian. "The Tokelau island migrant study." International Journal of Epidemiology (1974)​

 

[Dhair]

Interesting find there, hamster.

One thing that has always confused me about pattern baldness is the "pattern" aspect that much more commonly affects males. If stress was the primary culprit responsible for hair follicles to shut down or shed or go into "sleep" phase, then why so broadly does it exhibit the classic pattern of receding hairline and bald spot on the crown? Of course many people, and commonly women as well, can experience "diffuse" thinning, and even lose their hair in random spots and patches uniformly around the scalp. The mainstream knowledge says that this form of baldness is responsible to "stress" where as the former is due to androgens. Hence why women commonly don't experience the former, although that is not to say it doesn't happen. For example I know female bodybuilders and athletes who commonly experience male pattern baldness, especially when taking androgens for athletic performance. I also personally knew a girl who had issues with a slightly receding hairlines and acne which worried her as a teenager, so her doctor said she had high androgens (for a female) and prescribed her estrogen supplement. Of course I begged her to quit taking it and showed her progesterone instead.

Danny Roddy explains this here:

 

[Travis]

Danny Roddy explains this here:

No mention of cytokines. This is the classic function of mast cells, largely considered immune cells. Mast cells also secrete TNFα—another cytokine which releases arachidonic acid by transcribing phospholipase A₂.

But he drops a bombshell study at [08:56]:

➪ Larson, Allison R. "A prostaglandin D‐synthase‐positive mast cell gradient characterizes scalp patterning." Journal of cutaneous pathology (2014)​

Coupled with just the Louis Garza study, alone, this almost provides hands-down proof that prostaglandin D₂ is the ultimate downstream factor.

Besides blood flow, another way to explain the localization could be density. It's well-known that lipoproteins are found with different densities; also well-known is that low-density ones—such as chylomicrons—carry more linoleic acid. Some scientists even believe—for good reason—that it's the fat content alone which determines the density of the lipoprotein, as unsaturated fatty acids are simply less dense. They are less dense (ρ=m/v) because they have both more volume—due to their double-bond kinks—and slightly lower mass, due to the less hydrogen atoms per carbon.

So you might even expect the uppermost area of any person to have more unsaturated fats because the low-density fatty acids rise to the top; this is, after all, what is seen after centrifuging blood lipids—separating them by density in that manner.

 

[Dhair]

No mention of cytokines. This is the classic function of mast cells, largely considered immune cells. Mast cells also secrete TNFα—another cytokine which releases arachidonic acid by transcribing phospholipase A₂.

But he drops a bombshell study at [08:56]:

Larson, Allison R. "A prostaglandin D‐synthase‐positive mast cell gradient characterizes scalp patterning." Journal of cutaneous pathology (2014)​

Coupled with just the Louis Garza study, alone, this almost provides hands-down proof that prostaglandin D₂ is the ultimate downstream factor.

Besides blood flow, another way to explain the localization could be density. It's well-known that lipoproteins are found with different densities; also well-known is that low-density ones—such as chylomicrons—carry more linoleic acid. Some scientists even believe—for good reason—that it's the fat content alone which determines the density of the lipoprotein, as unsaturated fatty acids are simply less dense. They are less dense (ρ=m/v) because they have both more volume—due to their double-bond kinks—and slightly lower mass, due to the less hydrogen atoms per carbon.

So you might even expect the uppermost area of any person to have more unsaturated fats because the low-density fatty acids rise to the top; this is, after all, what is seen after centrifuging blood lipids—separating them by density in that manner.

No mention of cytokines. This is the classic function of mast cells, largely considered immune cells. Mast cells also secrete TNFα—another cytokine which releases arachidonic acid by transcribing phospholipase A₂.

But he drops a bombshell study at [08:56]:

➪ Larson, Allison R. "A prostaglandin D‐synthase‐positive mast cell gradient characterizes scalp patterning." Journal of cutaneous pathology (2014)​

Coupled with just the Louis Garza study, alone, this almost provides hands-down proof that prostaglandin D₂ is the ultimate downstream factor.

Besides blood flow, another way to explain the localization could be density. It's well-known that lipoproteins are found with different densities; also well-known is that low-density ones—such as chylomicrons—carry more linoleic acid. Some scientists even believe—for good reason—that it's the fat content alone which determines the density of the lipoprotein, as unsaturated fatty acids are simply less dense. They are less dense (ρ=m/v) because they have both more volume—due to their double-bond kinks—and slightly lower mass, due to the less hydrogen atoms per carbon.

So you might even expect the uppermost area of any person to have more unsaturated fats because the low-density fatty acids rise to the top; this is, after all, what is seen after centrifuging blood lipids—separating them by density in that manner.

That's interesting, because a lot of guys on hair loss forums have resorted to putting various PUFA oils on their heads with the reasoning being that the scalp "naturally" has a higher concentration of linoleic acid. How they came to the conclusion that this is somehow lacking in MPB, I have no idea.

 

[sladerunner69]

No mention of cytokines. This is the classic function of mast cells, largely considered immune cells. Mast cells also secrete TNFα—another cytokine which releases arachidonic acid by transcribing phospholipase A₂.

But he drops a bombshell study at [08:56]:

➪ Larson, Allison R. "A prostaglandin D‐synthase‐positive mast cell gradient characterizes scalp patterning." Journal of cutaneous pathology (2014)​

Coupled with just the Louis Garza study, alone, this almost provides hands-down proof that prostaglandin D₂ is the ultimate downstream factor.

Besides blood flow, another way to explain the localization could be density. It's well-known that lipoproteins are found with different densities; also well-known is that low-density ones—such as chylomicrons—carry more linoleic acid. Some scientists even believe—for good reason—that it's the fat content alone which determines the density of the lipoprotein, as unsaturated fatty acids are simply less dense. They are less dense (ρ=m/v) because they have both more volume—due to their double-bond kinks—and slightly lower mass, due to the less hydrogen atoms per carbon.

So you might even expect the uppermost area of any person to have more unsaturated fats because the low-density fatty acids rise to the top; this is, after all, what is seen after centrifuging blood lipids—separating them by density in that manner.

I don't think he agrees that cytokines should be the focus when considering the function of mast cells. I think he believes that they simply must be producing as much energy as possible.

 

[Travis]

I don't think he agrees that cytokines should be the focus when considering the function of mast cells. I think he believes that they simply must be producing as much energy as possible.

(I caught that one as well,)

That's interesting, because a lot of guys on hair loss forums have resorted to putting various PUFA oils on their heads with the reasoning being that the scalp "naturally" has a higher concentration of linoleic acid. How they came to the conclusion that this is somehow lacking in MPB, I have no idea.

Really? That would be interesting to know if the scalp really does have a higher concentration in linoleic acid—precursor for prostaglandin D₂. I threw that idea out without really knowing if it had any real consequence, but maybe it does? It would be interesting to see if hair loss is really found along a linoleic acid gradient, one that is superimposable over the prostaglandin D₂ synthase gradient.

Someone needs to channel Linus Pauling and get to the bottom of this.. . .

 

[Dhair]

(I caught that one as well,)
Really? That would be interesting to know if the scalp really does have a higher concentration in linoleic acid—precursor for prostaglandin D₂. I threw that idea out without really knowing if it had any real consequence, but maybe it does? It would be interesting to see if hair loss is really found along a linoleic acid gradient, one that is superimposable over the prostaglandin D₂ synthase gradient.

Someone needs to channel Linus Pauling and get to the bottom of this.. . .

Maybe a more accurate way to describe it is that they believe linoelic acid is important to focus on because it is somehow required in order to maintain a healthy scalp. Again, I don't see why this would be the case, but bear in mind that they think increasing prostaglandins in general is good for hair growth.

 

[Travis]

Maybe a more accurate way to describe it is that they believe linoelic acid is important to focus on because it is somehow required in order to maintain a healthy scalp. Again, I don't see why this would be the case, but bear in mind that they think increasing prostaglandins in general is good for hair growth.

Well, prostaglanin F2α, has been shown to stimulate hair growth. The fact that some increase, while some inhibit, hair growth makes a good case that they're involved in controlling the hair cycle through the transforming growth factor (TGF) class of peptide hormones. These rise and fall in ways mirroring the hair cycle, and they release arachidonic acid.

But prostaglandin D₂ is, undeniably, terrible for hair growth. There are four different PPAR receptors (α, β, γ, δ), and I think they all sense different prostaglandins (prostaglandin J₂ is the highest affinity ligand for PPARγ, while prostaglandin D₂ the highest affinity ligand for PPARα. I don't know anything about the other two.) . This would be how the cell creates proteins in response to different prostaglandins, and I think it might be helpful to find‐out which one controls the keratins: The main protein of hair.

I found an interesting study on the distribution of fatty acids across the entire head and scalp. Unfortunately, they group linoleic acid in with palmitoleic acid, so you can't differentiate between these two. This is especially annoying considering that this is the only pair they had grouped together.

Kotani, Akira, and Fumiyo Kusu. "HPLC with electrochemical detection for determining the distribution of free fatty acids in skin surface lipids from the human face and scalp." Archives of Dermatological Research (2002)
​

But nonetheless, there is a pattern. This might be surprising for some; to know that oleic acid can preferentially be found on the chin and nose—on the mid‐line. This is not the strangest study that I've seen, but in the top 10% for sure.

But this one alone can't say much about linoleic acid (18:2) due to it's being paired with palmitoleic acid (16:1). I can only guess this is becuase they both elute in tandem down the chromatography column—or 'comigrate' as they generally say.

 

[Scenes]

@Travis

Have you read any of swisstemples’ work? It’s becoming very similar.

http://swisstemples.com/the-prostaglandin-protocol/

 

[Travis]

@Travis

Have you read any of swisstemples’ work? It’s becoming very similar.

The Prostaglandin protocol | swissTemples

I've probably read nearly everything that website seems based‐on. The Louis Garza studies, and articles, are the best evidence for the incrimination of prostaglandin D₂ (and the one above, given by Danny Roddy.) Another drug that interferes with the prostaglandin signalling directly is oleuropein and oleocanthal. It inhibits COX‐2 better than ibuprofen, and probably has other functions as well.

And there's quite a bit more evidence showing prostaglandins E₂ and F₂α stimulate hair growth—probably more than any one person will ever read. Prostaglandins F₂α was originally found to stimulate the growth of eyelashes. These have radically‐different hair cycles, and eyelashes are unique on one respect, see below:

Johnstone, Murray A., and Daniel M. Albert. "Prostaglandin-induced hair growth." Survey of ophthalmology 47 (2002): S185-S202.

[Notice it was published in an opthalmology journal.]​

"SYNCHRONY AND DURATION: Although the hair cycle in many animals is synchronous, in humans it is asynchronous. The entire cycle varies in length depending on location in the body. On the scalp vertex, hair grows at a rate of 0.40 mm per day, and scalp hair may grow for as long as 6 years. Of the 100,000 hairs on the scalp, approximately 84% are in anagen stage, 2% in catagen, 14% in telogen, and about 70–100 are shed daily. A much shorter anagen phase and relatively longer telogen phase characterize eyelashes and eyebrows compared to scalp hair, and they have the lowest ratio of anagen to telogen follicles. Eyelashes grow for approximately 30 days, undergo quiescence for 15 days, and remain dormant for about 100 days. The total length of the cycle is reported to be 5 months. The growth phase of the cycle in eyebrows is approximately 6 months with an equal period of rest." ―Johnstone
​

So I'm not even sure that prostaglandins F₂α will work anywhere else; and even if it did, drugs that totally inhibit all prostaglandins could be more effective.

The needling sounds like it could be a good idea, but I think it's important to consider cytokines as well—the signals which not only produce prostaglandins, but nitric oxide too (through upregulation of nitric oxide synthase).

Is using needling and prostaglandin E₂ enough to offset the actions of a high cytokine profile dominated by interferon‐γ? I know it might sound crazy, but checking out hidden food allergies may be important as well. Cytokine profiles correlate well with hair loss, and so do genetic polymorphisms related to interleukin‐1.

Some of these cytokines are constantly upregulating the machinery to produce prostaglandins, so I think these should be kept-in-mind as well.
The mineralcorticoid receptor transcribes for TGF-1β, and also plays a role in producing interferon‐γ because it chaperones cyclophilins to the nucleus—which are the transcription factors for interferon‐γ (through YY1). The cyclophilins are what cyclosporin and FK-506 bind to, and inhibit—the most effective drugs for hair loss, and certainly more effective than prostaglandin E₂.

But you'd think that a prostaglandin D₂ inhibitor would be more effective yet, but I can't find any clinical demonstration of this. I know they're out there, and I'm pretty sure there's a book on GoogleBooks called "Inhibitors of Prostaglandin D₂ Synthase" that I haven't gotten around to reading yet.

 

[Scenes]

I've probably read nearly everything that website seems based‐on. The Louis Garza studies, and articles, are the best evidence for the incrimination of prostaglandin D₂ (and the one above, given by Danny Roddy.) Another drug that interferes with the prostaglandin signalling directly is oleuropein and oleocanthal. It inhibits COX‐2 better than ibuprofen, and probably has other functions as well.

And there's quite a bit more evidence showing prostaglandins E₂ and F₂α stimulate hair growth—probably more than any one person will ever read. Prostaglandins F₂α was originally found to stimulate the growth of eyelashes. These have radically‐different hair cycles, and eyelashes are unique on one respect, see below:

Johnstone, Murray A., and Daniel M. Albert. "Prostaglandin-induced hair growth." Survey of ophthalmology 47 (2002): S185-S202.

[Notice it was published in an opthalmology journal.]​

"SYNCHRONY AND DURATION: Although the hair cycle in many animals is synchronous, in humans it is asynchronous. The entire cycle varies in length depending on location in the body. On the scalp vertex, hair grows at a rate of 0.40 mm per day, and scalp hair may grow for as long as 6 years. Of the 100,000 hairs on the scalp, approximately 84% are in anagen stage, 2% in catagen, 14% in telogen, and about 70–100 are shed daily. A much shorter anagen phase and relatively longer telogen phase characterize eyelashes and eyebrows compared to scalp hair, and they have the lowest ratio of anagen to telogen follicles. Eyelashes grow for approximately 30 days, undergo quiescence for 15 days, and remain dormant for about 100 days. The total length of the cycle is reported to be 5 months. The growth phase of the cycle in eyebrows is approximately 6 months with an equal period of rest." ―Johnstone
​

So I'm not even sure that prostaglandins F₂α will work anywhere else; and even if it did, drugs that totally inhibit all prostaglandins could be more effective.

The needling sounds like it could be a good idea, but I think it's important to consider cytokines as well—the signals which not only produce prostaglandins, but nitric oxide too (through upregulation of nitric oxide synthase).

Is using needling and prostaglandin E₂ enough to offset the actions of a high cytokine profile dominated by interferon‐γ? I know it might sound crazy, but checking out hidden food allergies may be important as well. Cytokine profiles correlate well with hair loss, and so do genetic polymorphisms related to interleukin‐1.

Some of these cytokines are constantly upregulating the machinery to produce prostaglandins, so I think these should be kept-in-mind as well.
The mineralcorticoid receptor transcribes for TGF-1β, and also plays a role in producing interferon‐γ because it chaperones cyclophilins to the nucleus—which are the transcription factors for interferon‐γ (through YY1). The cyclophilins are what cyclosporin and FK-506 bind to, and inhibit—the most effective drugs for hair loss, and certainly more effective than prostaglandin E₂.

But you'd think that a prostaglandin D₂ inhibitor would be more effective yet, but I can't find any clinical demonstration of this. I know they're out there, and I'm pretty sure there's a book on GoogleBooks called "Inhibitors of Prostaglandin D₂ Synthase" that I haven't gotten around to reading yet.

But swisstemples found and used a few different things to block pgd2 and even applied pge2 powder directly on his scalp.

This was over 2 years ago i think. Have we heard anything since? Hardly. I assume that to mean it didn’t work.

 

[eddiem991]

But swisstemples found and used a few different things to block pgd2 and even applied pge2 powder directly on his scalp.

This was over 2 years ago i think. Have we heard anything since? Hardly. I assume that to mean it didn’t work.

Why? Maybe he has better things to do now when he has his hair?

 

[eddiem991]

@Travis How would you explain people taking anabolic steroids getting hairloss (bodybuilders)? Maybe stresses the body or causes hormonal imbalanses? If the DHT hypothesis is incorrect (hairfollice sensitivity), why does hair transplants work? I know these may be tough qusestions. I really enjoy reading your answers, so intersesting!

 

[Travis]

@Travis How would you explain people taking anabolic steroids getting hairloss (bodybuilders)? Maybe stresses the body or causes hormonal imbalanses? If the DHT hypothesis is incorrect (hairfollice sensitivity), why does hair transplants work? I know these may be tough qusestions. I really enjoy reading your answers, so intersesting!

I just looked into this yesterday, and I think I can explain it perfectly.

Interferon-γ, like prostaglandin D₂ and cortisol, is one of those things almost synonymous with hair loss. I have seen studies with mice expressing interferon-γ on the skin, and balding ensues. Also, interferon-γ knockout mice were found resistant to induced-alopecia. Interferon-γ has one canonical function, and that is to upregulate the transcription of phospholipase A₂. So then, you'd also probably expect mice expressing phospholipase A₂ to have alopecia; this is also the case—nearly indistinguishable from interferon-γ-expressing mice. The function of phospholipase A₂ is to release arachidonic acid—the prostaglandin precursor—from the sn-2 position of cell membrane phospolipids.

When looking at cytokines, you will find many. There are over seventeen interleukin types, three interferons, a few tumor necrosis factors, and a few more. However, some cytokines are actually beneficial (i.e. IL-10, IL-4) . . . and some are nearly irrelevant to hairloss. The ones which cause the most damage are interferon-γ, tumor necrosis factor, and interleukin-1 (both α and β).

Androgens actually cause hair growth, believe it or not, and androgen receptors are expressed on hair papilla cells. The beard has over twice the density as the scalp—obviously a prime example of androgens. Valerie Randall has shown that androgens stimulate hair growth on the scalp, so there is no way that androgens can directly cause hair loss. Androgens are nearly always anabolic.

But they indirectly cause hair loss in two ways. The first of which is through the adrenals, an organ expressing androgen receptors. These have been localized by immunohistochemistry, a technique where antibodies are attached to a fluorescent molecule and visualized. Dozens of studies also show that castration at an early age shifts the corticosteroid profile, leading to a more female phenotype. Different species are different, but human males have higher cortisol than females—a difference which changes after menopause, so perhaps its estrogen plays more of a role.

So there's that, but there's another:

The thymus is under control of androgens, and the thymus produces all T-cells of the body. There are two main type of thymus cells: thymus helper cells type one (TH1), and thymus helper cells type two (TH2). These secrete different cytokines, and different cytokine profiles are found in males. This makes sense, as estrogen would need to suppress certain types of immunity during pregnancy (as to not to reject the embryo). It has been found that males have a cytokine profile dominated by TH1 cells which secrete and interferon-γ and interleukin-2. Females have more TH2 cells, and these secrete the more protective interleukin-4 (among others). It has been experimentally-determined that lowering testosterone lowers interferon-γ, powerfully—like a 75% percent reduction. This is, in my opinion, why finasteride works. I don't think that it could change the corticosteroid profile enough to make much of a difference.

Cyclosporine works mainly by preventing the transcription of interferon-γ. It's target, cyclophilin-12, conjugates with the YY1 transcription factor in the nucleus to transcribe interferon-γ. Also found to bind and activate/repress YY1 is a smaller FKBP, making the mechanisms of hair-growing FK-506 (Tacrolimus) indistinguishable from that of cyclosporine. There is clinical evidence of this, and plenty of it. I'm certain that you could find over fifty studies right now showing that cyclosporine lowers interferon-γ in patients. This is basically how it works, and hypertrichosis is the most common side effect.

Leishmaniasis is a tropical infection known to cause interferon-γ release from T-cells. Leishmaniasis is known to cause alopecia in dogs.

Cytokine profiles in alopecia areata are often measured, and they often show increased interferon-γ in the more serious cases. The cytokine profiles in male pattern baldness are not commonly measured, as nearly all scientists are laboring under the same misconceptions and prejudice.

Although I haven't checked, I would imagine that finasteride lowers interferon-γ by over 50%. I am fairly certain that finasteride works through this mechanism: by acting on the thymus and lowering interferon gamma.

[Citations available upon request. I have scientific evidence for every statement made above.]

 

[eddiem991]

I just looked into this yesterday, and I think I can explain it perfectly.

Interferon-γ, like prostaglandin D₂ and cortisol, is one of those things almost synonymous with hair loss. I have seen studies with mice expressing interferon-γ on the skin, and balding ensues. Also, interferon-γ knockout mice were found resistant to induced-alopecia. Interferon-γ has one canonical function, and that is to upregulate the transcription of phospholipase A₂. So then, you'd also probably expect mice expressing phospholipase A₂ to have alopecia; this is also the case—nearly indistinguishable from interferon-γ-expressing mice. The function of phospholipase A₂ is to release arachidonic acid—the prostaglandin precursor—from the sn-2 position of cell membrane phospolipids.

When looking at cytokines, you will find many. There are over seventeen interleukin types, three interferons, a few tumor necrosis factors, and a few more. However, some cytokines are actually beneficial (i.e. IL-10, IL-4) . . . and some are nearly irrelevant to hairloss. The ones which cause the most damage are interferon-γ, tumor necrosis factor, and interleukin-1 (both α and β).

Androgens actually cause hair growth, believe it or not, and androgen receptors are expressed on hair papilla cells. The beard has over twice the density as the scalp—obviously a prime example of androgens. Valerie Randall has shown that androgens stimulate hair growth on the scalp, so there is no way that androgens can directly cause hair loss. Androgens are nearly always anabolic.

But they indirectly cause hair loss in two ways. The first of which is through the adrenals, an organ expressing androgen receptors. These have been localized by immunohistochemistry, a technique where antibodies are attached to a fluorescent molecule and visualized. Dozens of studies also show that castration at an early age shifts the corticosteroid profile, leading to a more female phenotype. Different species are different, but human males have higher cortisol than females—a difference which changes after menopause, so perhaps its estrogen plays more of a role.

So there's that, but there's another:

The thymus is under control of androgens, and the thymus produces all T-cells of the body. There are two main type of thymus cells: thymus helper cells type one (TH1), and thymus helper cells type two (TH2). These secrete different cytokines, and different cytokine profiles are found in males. This makes sense, as estrogen would need to suppress certain types of immunity during pregnancy (as to not to reject the embryo). It has been found that males have a cytokine profile dominated by TH1 cells which secrete and interferon-γ and interleukin-2. Females have more TH2 cells, and these secrete the more protective interleukin-4 (among others). It has been experimentally-determined that lowering testosterone lowers interferon-γ, powerfully—like a 75% percent reduction. This is, in my opinion, why finasteride works. I don't think that it could change the corticosteroid profile enough to make much of a difference.

Cyclosporine works mainly by preventing the transcription of interferon-γ. It's target, cyclophilin-12, conjugates with the YY1 transcription factor in the nucleus to transcribe interferon-γ. Also found to bind and activate/repress YY1 is a smaller FKBP, making the mechanisms of hair-growing FK-506 (Tacrolimus) indistinguishable from that of cyclosporine. There is clinical evidence of this, and plenty of it. I'm certain that you could find over fifty studies right now showing that cyclosporine lowers interferon-γ in patients. This is basically how it works, and hypertrichosis is the most common side effect.

Leishmaniasis is a tropical infection known to cause interferon-γ release from T-cells. Leishmaniasis is known to cause alopecia in dogs.

Cytokine profiles in alopecia areata are often measured, and they often show increased interferon-γ in the more serious cases. The cytokine profiles in male pattern baldness are not commonly measured, as nearly all scientists are laboring under the same misconceptions and prejudice.

Although I haven't checked, I would imagine that finasteride lowers interferon-γ by over 50%. I am fairly certain that finasteride works through this mechanism: by acting on the thymus and lowering interferon gamma.

[Citations available upon request. I have scientific evidence for every statement made above.]

Great summary, so could one say that it all boils down to an over active/upregulated immune system, some kind of autoimmune disorder or even a compromised immune system?

About cortisol: So it causes hairloss, but not sure exactly how it does it, but directly or indirectly it must effect the hair follice somehow...

Cortisol suppreses the immune system but if the immune system is causing hairloss, cortisol should be able to stop it, or atleast halt it, right? Could this be a case like insulin resistance, where the body gets desenitized to the chronic over exposure of cortisol due to inflammation?

Another interesting thing is looking at the long-term effects of hydrocortisone use: "include osteoporosis, upset stomach, physical weakness, easy bruising, and yeast infections"

My theory: Long term stress (fight or flight response) "shuts down" the energy expensive digestive tract which causes fungus like Candida, bacteries and/or microbes to take advantage which leads to over growth of these harmfull pathogens. Then eating for example Gluten (if you are allergic) your intesine will become permable for the pathogens to spread into the blood stream which causes inflamation. Togheter with PUFA, nutritional deficencies and stress the immune system is weak and running crazy.

What do you think Travis?

 

[Travis]

Great summary, so could one say that it all boils down to an over active/upregulated immune system, some kind of autoimmune disorder or even a compromised immune system?

About cortisol: So it causes hairloss, but not sure exactly how it does it, but directly or indirectly it must effect the hair follice somehow...

Cortisol suppreses the immune system but if the immune system is causing hairloss, cortisol should be able to stop it, or atleast halt it, right? Could this be a case like insulin resistance, where the body gets desenitized to the chronic over exposure of cortisol due to inflammation?

Another interesting thing is looking at the long-term effects of hydrocortisone use: "include osteoporosis, upset stomach, physical weakness, easy bruising, and yeast infections"

My theory: Long term stress (fight or flight response) "shuts down" the energy expensive digestive tract which causes fungus like Candida, bacteries and/or microbes to take advantage which leads to over growth of these harmfull pathogens. Then eating for example Gluten (if you are allergic) your intesine will become permable for the pathogens to spread into the blood stream which causes inflamation. Togheter with PUFA, nutritional deficencies and stress the immune system is weak and running crazy.

What do you think Travis?

Cortisol will certainly cause hair loss when applied directly to the skin. This could be by upregulating TGF-β, something aldosterone has been shown to do. Also, the immunophilins form a complex with the mineralcorticoid receptor—a molecular chaperone. The immunophilins are responsible for transcribing interferon-γ.

But immune responses can also upregulate cortisol, so there's no way to determine that the epidemiological correlations between cortisol and hair loss are a cause of cortisol or immune activation.

I can tell you one thing: Animals which have had their adrenal cortex removed will grow more hair. This was a very common finding in the '40s and '50s. The effects of cortisol on hair are undeniably bad, and it has even been shown to reduce growth rates on isolated follicles. How exactly this happens is disputable, but there are many overlaps between cortisol, mast cells, growth factors, and immune cytokines.