Fascinating New Paper On Hair Loss

Philjay

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I disagree. When I was a younger man and hysterical about hair loss, I took Finasteride 10mg/day. My scalp hair flourished. I had so much more hair. No question about it but it also shrunk my testicles and took all my libido so I had to quit.
The author said DHT is found in higher amounts in the scalp of AGA sufferers and DHT/Estrogen play a role muscle tension so if I reduce the microflora of the scalp, the sebum, that reduces DHT and its affects----with a anti dandruff shampoo? What a thought?

Thats why nizoral active ketocanazole can help restore hair loss , like it can also help acne and reduce oil in certain 5 a sufferers.
 

Hairfedup

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I would suggest that Aa its going to be vital as you say to first locate the hormonal issue , is it too much testosterone converting to dht , or is it perhaps far to much 5 alpha reductase activity? These are the issues that are going to be most likely key .
As an example,
Person 1' uses steroids to build muscle, his skin clears up but his hair starts to fall out.
Person 2. Uses steroids to build muscle, his skin becomes very spotty and oily but his hair is perfectly fine.

Person 1 sees a huge amount of 5alpha reductase activity in the scalp.
Person 2 in the skin.

Another example, John is in his mid 20s and starts seeing a rapidly shedding crown, however he has no other markers for Aa, this is most likely mpb as it seems to be more visible at the crown , and its likely treatment would be through invasive tactics.
In my opinion Aa can be treated, mpb can be covered either with surgery or dna retranscription.

Yes im of the opinion that AA can be treated but I was certain that maybe I'm estrogenic with low test! Unfortunately no bloodwork done yet until next week. Once done I can try start a regime steering toward parameters that will fix my terrible A...im sure it is treatable. Do you suffer from AA?
 

Philjay

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I dont suffer with it, but im fascinated by it and why certain individuals have it while others with every marker dont, I am interested in helping treat it.
I look fowards to your bloods, perhaps you just have too much shbg and its causing the issue, too much testosterone is being converted where you dont want, and it might just need a tweak. Best case scenario .
Im Phil btw, virtual hand shake. Vhs.
 

Hairfedup

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I dont suffer with it, but im fascinated by it and why certain individuals have it while others with every marker dont, I am interested in helping treat it.
I look fowards to your bloods, perhaps you just have too much shbg and its causing the issue, too much testosterone is being converted where you dont want, and it might just need a tweak. Best case scenario .
Im Phil btw, virtual hand shake. Vhs.

Hey Phil thanks for the info...yeah the bloodwork shall answer the most important questions I guess....I too am fascinated by my AA because in many ways, it just doesn't make sense haha.
 

Hairfedup

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It never does lol.

Lool indeed. Looking forward to the bloodwork and maybe we can discuss it, then. If you want you can check out my earlier thread, but no need to. I'm just confused because I've been following a user by the name of Elephanto's protocol in which he tries to eliminate all estrogen and up his test, but this could be impacting me in worse ways lol. Then again, it could be helping....baldness is some complex ***t man.
 

Philjay

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Can you link me to your thread I will have a look through.
Yes I am sure we will have a lot to discuss , hopefully we can find a solution.
 

franc0

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The downstream effects of prostaglandin D₂ need to be explored further, but it could be enough to say that it acts as a pressor agent in blood vessels and a bronchoconstrictor in the lungs. Prostaglandin E₂ has opposite effects in the arteries, in the airways, and on hair growth—lending support to the idea that the final downstream mechanism could simply be hypoxia. But again, you're on your own here; nobody really has explored these depths and the case against prostaglandin D₂ is epidemiological mostly, although it has been shown to decrease hair growth when applied directly.

I think it's either the pressor effect on the vessel walls or the Ca²⁺ influx, but these two events are inseparable because it's the Ca²⁺ ion which ultimately causes vasoconstriction through myosin light chain on the vessel wall.
Travis mate, you're such a smart c*nt, what protocol do you have for keeping your hair?
 

AretnaP

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He's right. Valerie Randall proved that DHT when applied directly actually stimulated hair growth.

I read it, and the article first starts out with a summary of nearly all observations regarding hair loss. He ends up concentrating on scalp tension, fibrosis, and calcification—with calcification being induced by androgens more‐or‐less directly:

'In mice, dose-dependent DHT and testosterone injections increase arterial calcification lesions by 300–400% [47].' ―Robert English

The mechanisms linking androgens to fibrosis are not very straightforward, and his final conculsion seems most centered around scalp tension. He does note that physical tension can induce cyclooxygenase‐2, and explains the prostaglandin D₂ in this manner, but I will point out that Garza had also found increased ptgds to match—this is the enzyme which creates prostaglandin D₂ from prostaglandin H₂; this enzyme is induced by cortisol, a steroid Robert English mentions not once.

Since the evidence linking prostaglandin D₂ to hair loss is so strong, I like to focus on that. I think the patterning is just as well explained by the microcirculation: The steroid transfer rate from blood binding proteins—such as cortisol transferred from albumin—has been proven to increase in microcirculatory regions. I think the ptgds gradient observed by Garza, and others, would be superimposable over the cortisol gradient since cortisol is the only thing shown to induce ptgds.


But since he focuses on fibrosis, calcification, and tension, the fundamental final pathway is more‐or‐less reduced blood flow. Prostaglandin D₂ has been shown in dozens of experiments to constrict the lungs, and also to constrict the blood vessels in a few others. One good thing about having reduced blood flow as the final mechanism, besides it being logical, is that it includes nearly all observations. As long reduced blood flow can be logically explained somehow, then most alternative explanations could have merit—disagreement coming only from the relative contributions of each particular one.

I think the two best explanations not touched on in the article for how androgens cause hair loss is through interferon-γ from the thymus and cortisol from the adrenals. In humans, androgens increase both of these and both can cause hair loss (as seen in mice overexpressing either interferon-γ or the mineralocorticoid receptor on the skin—both are nearly completely hairless).

But even if calcium plays only a minor role, people should get enough vitamin K and vitamin D to keep their arteries from calcifying. Warfarin, a vitamin K antagonist, causes rapid calcification of the arteries. Vitamin K is used as a cofactor for the enzyme which creates the γ-carboxyglutamate domain on proteins; this domain strongly binds Ca²⁺ ions and keeps them from precipitating in the blood (with phosphate).
Propecia is somewhat effective therefore MBP is caused by DHT, do not question, do not think.

Take your prozac, watch television, and go to work, America.
 

Philjay

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Propecia will not cure mpb the issue will always remain.

People see results with potassium channel openers, with glyceryl trinitrate or with propecia, ive seen great results with pge2 in clients, as personally I think the link is raising pge2- and at the same time lowering pgd2.

Nicotinic acid may be useful in flushing pgd2 into the blood stream. Lowering its actual binding. But I think we need to exhaust all parameters and get a detailed observation.
The reason why dht applied to the scalp works in some is that it saturates the receptors , the rebound affect lowers dht and increases hair growth. There is no one glove fits all.
 
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Travis

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...what protocol do you have for keeping your hair?
I don't do anything besides avoid linoleic acid right now, but I think cyclosporine and spironolactone would certainly help; anything which prevents γ-interferon production or cortisol should be helpful. I also did find that vitamin D is essential, but I think it plays a relatively minor role in most cases. The hair keratin 31 gene is under the control of the vitamin D receptor so it's impossible to form hair without it (probably why vitamin D receptor null mice are totally hairless).

There are so many studies showing the prostaglandin pathway causes hair loss: from genetic cyclooxygenase upregulation, interferon-γ overexpression, and even the feeding of oxidized oils.

If someone has the money and the inclination, than I would think topical cyclosporine + spironolactone would be the best. This would inhibit both interferon-γ and block the mineralocorticoid receptor, two things that powerfully upregulate prostaglandin D₂.

Avoiding linoleic acid could seem somewhat restrictive, but we do have some good things to choose from; cheese, beef, coconuts, chocolate, fruit, and many vegetables are all low in linoleic acid. The best way to lower prostaglandin D₂ is through eliminating its only precursor.
 

Hairfedup

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I don't do anything besides avoid linoleic acid right now, but I think cyclosporine and spironolactone would certainly help; anything which prevents γ-interferon production or cortisol should be helpful. I also did find that vitamin D is essential, but I think it plays a relatively minor role in most cases. The hair keratin 31 gene is under the control of the vitamin D receptor so it's impossible to form hair without it (probably why vitamin D receptor null mice are totally hairless).

There are so many studies showing the prostaglandin pathway causes hair loss: from genetic cyclooxygenase upregulation, interferon-γ overexpression, and even the feeding of oxidized oils.

If someone has the money and the inclination, than I would think topical cyclosporine + spironolactone would be the best. This would inhibit both interferon-γ and block the mineralocorticoid receptor, two things that powerfully upregulate prostaglandin D₂.

Avoiding linoleic acid could seem somewhat restrictive, but we do have some good things to choose from; cheese, beef, coconuts, chocolate, fruit, and many vegetables are all low in linoleic acid. The best way to lower prostaglandin D₂ is through eliminating its only precursor.

Thanks Travis...super interesting.

Anyone figured out why hairless cats are hairless?
 

Travis

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Thanks Travis...super interesting.

Anyone figured out why hairless cats are hairless?
Not yet, but Barbara Gandolfi might know:

Gandolfi, Barbara. "The naked truth: Sphynx and Devon Rex cat breed mutations in KRT71." Mammalian Genome (2010)

Judging by the title, you'd have to think that keratin #71 is involved. It is probably worth noting that in people, all the ten or so (type I) hair keratins have PPAR response elements with the exception of keratin #31—which is transcribed by the vitamin D receptor. The PPAR receptors are nuclear receptors and transcription factors, travelling into the nucleus to transcribe for proteins upon ligand activation. Half of the hair keratins have PPARα response elements, and half have PPARγ response elements. But since most males seem to have no loss of PPAR ligands or vitamin D, it could be the cardiovascular effects of prostaglandin D₂ which are most important—tending towards ischemia on account of its pressor effects?

Now what is going on here? I mean . . . WTF is going on with this cat?

Sphynx-Standing.ashx


It looks like a plucked chicken—and something Dr. Evil would like. And it looks like it could get cold in the wintertime.

This hairless mutation seems to be pretty well understood. The keratin #71 is found on the inner root sheath and mutations here can cause curliness. This is easy to understand once you know that this keratin protein has an α-helix:

pauling.png
keratin.png
Taken from Pauling 1951–1953.

A polymorphism in the keratin α-helix could give rise to curly hair due to differential twisting with neighboring keratin strands, perhaps twisting at at a different pitch with the ¹⁵¹Arg→Trp substitution. Arginine is a high‐affinity amino acid that can form intermolecular bridges and tryptophan cannot do this. A single amino acid substitution of a single hair keratin create curly hair in dogs and sheep:

'The keratin protein consists of three domains: a head domain, a low-complexity coiled-coil tail domain, and the helix-forming α-helical rod domain. The α-helical rod domain of KRT71 plays an important role in forming heteropolymers of specific type I and type II cytokeratin through interactions of these domains.' ―Gandolfi

'A single nucleotide polymorphism, Arg¹⁵¹Trp, has been recently identified in curly hair in dogs. In cattle, an 8-bp deletion occurring in exon 1 causes an early truncated KRT71 protein resulting in a curly-hair coat.' ―Gandolfi

But it gets worse: More extreme changes in keratin #71 genes can lead to total hairlessness—as seen in the Sphinx Cat.

'DNA samples were collected from the cats noninvasively...' ―Gandolfi

'All nine exons of KRT71 were amplified by PCR from genomic DNA of 24 cats (Supplementary Table 2), including seven rexoid breeds, three hairless breeds, and a control, domestic shorthair.' ―Gandolfi

cat.png

'The resulting protein has a 35-amino-acid deletion at the 30 C-terminus end of the α-helical rod domain.' ―Gandolfi

'Our current study demonstrates the importance of the α-helical rod domain of KRT71 in hair formation in cats.' ―Gandolfi

And the Sphinx mutation is thought to have an extra 43 DNA base pair insertion, a section of which creates a premature stop codon leading to a truncated protein.

'Comparison of cDNA with genomic sequences of KRT71 suggested that the GT dinucleotide sequence 44 bp downstream of the original splice site serves as an alternative splicing donor site in the Sphynx mutant allele. Thus, an alternative splice site is recognized at base pair 44 in the modified exon 4. This alteration causes a stop codon at position 27 in the insertion, leading to a truncated KRT71. The truncated protein deletes the majority of the α-helical rod domain that plays an important role in forming heteropolymers of specific type I and type II cytokeratin through interactions of these domains. Together, sequence alterations in exon 7 and a truncated protein affecting the α-helical rod domain could also affect the formation of heteropolymers of specific type I and type II cytokeratins, cellular targeting, receptor binding, or proper folding of the protein after translation.' ―Gandolfi

So this mutation totally abrogates the hair, going to show that the loss of just one keratin could perhaps cause hair loss. Mice lacking the vitamin D receptor cannot transcribe kertain #31, and very well could be hairless for this reason alone. Mice lacking PPARγ are hairless as well; this receptor is responsible for transcribing a five or so type I hair keratins.

Xie, Zhongjion. "Lack of the vitamin D receptor is associated with reduced epidermal differentiation and hair follicle growth." Journal of investigative dermatology (2002)
Pauling, Linus. "The structure of proteins: two hydrogen-bonded helical configurations of the polypeptide chain." Proceedings of the National Academy of Sciences (1951)
Karnik, Pratima. "Hair follicle stem cell-specific PPARγ deletion causes scarring alopecia." Journal of Investigative Dermatology (2009)
Pauling, Linus. "Compound helical configurations of polypeptide chains: structure of proteins of the α-keratin type." Nature (1953)
 
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Philjay

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Jan 23, 2018
Messages
65
Not yet, but Barbara Gandolfi might know:

Gandolfi, Barbara. "The naked truth: Sphynx and Devon Rex cat breed mutations in KRT71." Mammalian Genome (2010)

Judging by the title, you'd have to think that keratin #71 is involved. It is probably worth noting that in people, all the ten or so (type I) hair keratins have PPAR response elements with the exception of keratin #31—which is transcribed by the vitamin D receptor. The PPAR receptors are nuclear receptors and transcription factors, travelling into the nucleus to transcribe for proteins upon ligand activation. Half of the hair keratins have PPARα response elements, and half have PPARγ response elements. But since most males seem to have no loss of PPAR ligands or vitamin D, it could be the cardiovascular effects of prostaglandin D₂ which are most important—tending towards ischemia on account of its pressor effects?

Now what is going on here? I mean . . . WTF is going on with this cat?

Sphynx-Standing.ashx


It looks like a plucked chicken—and something Dr. Evil would like. And it looks like it could get cold in the wintertime.

This hairless mutation seems to be pretty well understood. The keratin #71 is found on the inner root sheath and mutations here can cause curliness. This is easy to understand once you know that this keratin protein has an α-helix (taken from 1950s Linus Pauling articles):

View attachment 8169 View attachment 8170

A polymorphism in the keratin α-helix could give rise to curly hair due to it twisting with neighboring strands at a different pitch—the ¹⁵¹Arg→Trp substitution. Arginine is a high‐affinity amino acid that can form intermolecular bridges, and tryptophan cannot do this. A single amino acid substitution of a single hair keratin can create curly hair in dogs and sheep.

'The keratin protein consists of three domains: a head domain, a low-complexity coiled-coil tail domain, and the helix-forming α-helical rod domain. The α-helical rod domain of KRT71 plays an important role in forming heteropolymers of specific type I and type II cytokeratin through interactions of these domains.' ―Gandolfi

'A single nucleotide polymorphism, Arg¹⁵¹Trp, has been recently identified in curly hair in dogs. In cattle, an 8-bp deletion occurring in exon 1 causes an early truncated KRT71 protein resulting in a curly-hair coat.' ―Gandolfi

But it gets worse: More extreme changes in keratin #71 genes can lead to total hairlessness—as seen in the Sphinx Cat.

'DNA samples were collected from the cats noninvasively...' ―Gandolfi

'All nine exons of KRT71 were amplified by PCR from genomic DNA of 24 cats (Supplementary Table 2), including seven rexoid breeds, three hairless breeds, and a control, domestic shorthair.' ―Gandolfi


'The resulting protein has a 35-amino-acid deletion at the 30 C-terminus end of the α-helical rod domain.' ―Gandolfi

'Our current study demonstrates the importance of the α-helical rod domain of KRT71 in hair formation in cats.' ―Gandolfi

And the Sphinx mutation is thought to have an extra 43 DNA base pair insertion, a section of which creates a premature stop codon leading to a truncated protein.

'Comparison of cDNA with genomic sequences of KRT71 suggested that the GT dinucleotide sequence 44 bp downstream of the original splice site serves as an alternative splicing donor site in the Sphynx mutant allele. Thus, an alternative splice site is recognized at base pair 44 in the modified exon 4. This alteration causes a stop codon at position 27 in the insertion, leading to a truncated KRT71. The truncated protein deletes the majority of the α-helical rod domain that plays an important role in forming heteropolymers of specific type I and type II cytokeratin through interactions of these domains. Together, sequence alterations in exon 7 and a truncated protein affecting the α-helical rod domain could also affect the formation of heteropolymers of specific type I and type II cytokeratins, cellular targeting, receptor binding, or proper folding of the protein after translation.' ―Gandolfi

So this mutation totally abrogates the hair, going to show that the loss of just one keratin could perhaps cause hair loss. Mice lacking the vitamin D receptor cannot transcribe kertain #31 and are most likely hairless for that reason alone, and mice lacking PPARγ are hairless as well; this is responsible for transcribing a handful of hair type I keratins.

Xie, Zhongjion. "Lack of the vitamin D receptor is associated with reduced epidermal differentiation and hair follicle growth." Journal of investigative dermatology (2002)
Pauling, Linus. "The structure of proteins: two hydrogen-bonded helical configurations of the polypeptide chain." Proceedings of the National Academy of Sciences (1951)
Karnik, Pratima. "Hair follicle stem cell-specific PPARγ deletion causes scarring alopecia." Journal of Investigative Dermatology (2009)
Pauling, Linus. "Compound helical configurations of polypeptide chains: structure of proteins of the α-keratin type." Nature (1953)
Like I said.. ish, genes
 
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