Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signaling pathways.

Br J Dermatol. 2017 Apr 12. doi: 10.1111/bjd.15577. [Epub ahead of print]
Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signaling pathways.

Michel L1,2, Reygagne P3, Benech P4,5, Jean-Louis F1,2, Scalvino S6, Ly Ka So S1, Hamidou Z3, Bianovici S3, Pouch J7, Ducos B7,8, Bonnet M1, Bensussan A1,2, Patatian A5, Lati E5,6, Wdzieczak-Bakala J9, Choulot JC10, Loing E11, Hocquaux M11.

BACKGROUND:
Male androgenetic alopecia (AGA) is the most common form of hair loss in men and is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined.
OBJECTIVES:
Herein, molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless/bald men with premature AGA and healthy volunteers.
RESULTS:
This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory and immunoglobulin-associated immune mediators were significantly over-expressed in AGA. In contrast, under-expressed genes appear to be associated with the Wnt/β-catenin and BMP/TGF-β signaling pathways. Although involvement of these pathways in hair follicle regeneration is well-described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin (POMC), as confirmed by RT-qPCR and immunohistochemistry. In addition, lower expression of CYP27B1 in AGA subjects supports the notion that changes in vitamin D metabolism contributes to hair loss.
CONCLUSION:
This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave way for new therapeutic approaches. This article is protected by copyright. All rights reserved.

does this mean that baldness is a phenotype expressed as an epigenetic response to environmental circumstances in ANY male?

OR

Does it mean that only SOME males are uniqueley epigenetically vulnerable to environmental circumstances (and studies like this outline the specific mechanics in those susceptible)?


I know that all the measures we take for natural regrowth have an impact that can influence the "pathways", but I want to know if I or we sufferers are genetically prone because we are fundamentally different to norwood 1s, or if we are fundamentally the same but our scalps just caved first because of "molecular events"?

The distinction is important because my overall health optimization measures would differ in either circumstance. like, I will know when I have hit my "ceiling" if I am genetically different, whereas if I think I'm genetically the same then I will continue to attempt to measure my health by hair vitality and never stop until it's rectified, which would be a torment if it's not actually possible for me...

In my view, I believe that "so-called" 'genetic' hair loss is very rare and that almost all AGA/MPB is most likely to be epigenetic. This could mean a very broad range of things. "Civilized" man is so departed from nature, especially in our food system that even consumption of organic food will fail to meet true nutritional needs.

This view point may appear extreme, but I can say that almost all diseases appear to be brought on by iatrogenic and epigenetic causes.

The paper speaks about several influences, one of them involves the actions of corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress.

Beyond that, this and others mentioned are all modifiable. Medicine has become a game of profit, patents and never the pursuit of true causation. Yet, there is enough independent research that reveals the answers. The problem though is that each person has unique reasons for their MPB combined with some very common reasons.

Yeah, that ironic stress about mpb that makes your mpb worse... lol and then when you find out that stress causes balding and you get the ultimate ironic stress because you can't stop stressing in order to stop baldness... lmao I should probably just get that sensoril you recommend.

So, you believe that it's fundamentally an environmental problem. If we were in our natural ancient environment, free from toxins, chemicals, stress,and radiation etc., and bathed in the suns light while we devour ridiculously nutrient dense mega brocalli and ancient super vitamin meat, that this shit would never have happened in the first place.

...and only now, in this modern world we are up against it.

My mind is shouting "but what about the women and the norwood 1 unhealthy guys"?

I suppose DHT can only be used as a weapon against us if it's actually present, so that explains women.

But those Norwood 1 men, with DHT rich scalps? wait you talked about this before. high blood dht means low tissue dht. But I can only imagine that they must just have a natural resilience to free radicals then, despite their unhealthy lifestyle... yet the balding man just can't seem to hack the free radicals and just ends up sprouting loads of androgen receptors, and falling into the spiral of events that culminate in hair loss..

So, i don't have balding genes, I have an unlucky inability to handle the free radical stress of modern living amongst other modern setbacks, and my body's revealing this via my hair.

There's a lot of really surprising things about the true reason(s) for most causes of MPB, and unfortunately, even a few pages are not enough foundation to adequately explain it. I believe about in as much as one-third of cases (in MPB) are set by what happens at the age of 7 to 8 years of age. 95% of people have malocclusion. The reason for this is environmental in nature. Some primitives (before the advent of civilized foods) were rarely exhibited to possess what is "normal" for us.

The nature of the blood-flow because of this developmental imperfection causes an elevated level of factors in the blood that increase the toxicity of androgens.

Since that aspect is only an estimated third of the problem, many with MPB have other contributing factors.

"Changes in vitamin D metabolism" sounds about right to me.

SOMETHING happens to trigger mpb. Some men have hair their whole lives and then suddenly at the random age of 56 start to lose their hair. So how is DHT the primary cause? If he has been walking around with it for 56 years and no problems?

There is a subtle but important distinction to be made when discussing DHTs role in hairloss.

first there is the simplistic view that DHT causes hairloss in those genetically susceptible. I don't think it's that straight forward.

However, I acknowledge that DHT while not being a straight forward cause, is implicated in the overall process. In an ideal world, it would not cause any problems. But if the body is inflamed and hormonally out of whack, sick chronically under the radar, that then the androgens are somehow damaging at that point to hair growth. an analogy would be "a drunk driver blaming a crash on his vehicle because the vehicle did the damage", because essentially we have a somehow unhealthy body yet we blame the androgens because they can be found elevated in the scalp doing the damage". in reality, cars and DHT are safe when operated by healthy bodies.

Hafþór Júlíus Björnsson doesn't look "unhealthy" to me. He's the world's strongest man... and balding!

Something must happen with the hair follicles themselves to become sensitive to DHT. For most men, the hair follicles are resistant for decades. Then, the hairs at the front and back are the first to change. They suddenly become sensitive.

As we know, Eunuchs don't go bald but when you inject testosterone/DHT into older Eunuchs they will start to lose hair rapidly. This is because the hair has been "waiting" for DHT for decades and cannot start the miniaturisation process without it. So when the DHT hits a 50 year old Eunuch.... all of his hair falls out within months.

CS,

Would love to hear more on your thoughts on the influence of childhood development on hair loss, and mitigating that influence.

I am one of those children that had malocclusions. One was fairly severe, one was very mild. Looking back, it was probably from sucking my thumb.
It was corrected in my teens with orthodontics, and I have nice straight teeth.

Is the damage already done? Is there anything specific/special to be done outside of the typical IH regimen? Thanks

ihavetinyfeet wrote:CS,

Would love to hear more on your thoughts on the influence of childhood development on hair loss, and mitigating that influence.

I am one of those children that had malocclusions. One was fairly severe, one was very mild. Looking back, it was probably from sucking my thumb.
It was corrected in my teens with orthodontics, and I have nice straight teeth.

Is the damage already done? Is there anything specific/special to be done outside of the typical IH regimen? Thanks

On what can be done now about it is only speculative, however it's one of the most interesting theories behind a so-called "genetic" disorder, because there is a true absence of gene factors (outside of only a few) that explain what is happening behind MPB. This alteration can be prevented absolutely, but only in formative years...Vitamin K2 for example plays a strong role in the formation of the mandible (wider cheekbones), better control over calcium, vitamin D, and bone differentiation. It is only anecdotal at this point that beyond the formative years, that vitamin K2 can improve the facial structure.

There are a few more details that for lack of time and space would complete the picture for this. So, there are some interventions...Properly dealing with toxic metals (having an influence inflammation cytokines in the blood) are an important defense. For a number of important reasons, a lot of detail on this cannot be shared on an open forum, because too many details (which are critical to get right) could cause some issues.

Very, very interesting that CS mentions what happens between the age of 7 and 8.

CS, are you referring to a strictly nutritional event that can set the stage,
or a psychological one (or a mixture) ?

I have been reading some interesting literature suggesting the heart isn't actually a pump.

http://www.anthromed.org/Article.aspx?artpk=521

It's got me rethinking some older theories CS and others have suggested within this forum.

There's so much to learn/uncover.

Live forever wrote:Very, very interesting that CS mentions what happens between the age of 7 and 8.

CS, are you referring to a strictly nutritional event that can set the stage,
or a psychological one (or a mixture) ?

I have been reading some interesting literature suggesting the heart isn't actually a pump.

http://www.anthromed.org/Article.aspx?artpk=521

It's got me rethinking some older theories CS and others have suggested within this forum.

There's so much to learn/uncover.

Yes, mainly vitamin D exposure and Vitamin K2 are necessary to properly form the facial anatomy. Dentists usually add to the problem of facial asymmetry.

I have avoided that subject here (the heart is not a pump), and am a very firm believer...the research started quite a long time ago (in the 1920's) and continued in the Journal of Circulation in 1988.

http://www.rsarchive.org/RelArtic/Marinelli/

My thoughts too CS.
And it becomes evidence of how insane Statins are, and will continue to be
until a new understanding of the human is brought to light.
(Not to mention the whole industry.)

Might be a coincidence or intentional, but your spiral/vortex avatar seems to relate to the subject.

With regard to epigenetics, what are your thoughts on emotions/thoughts as living systems
that can actually surround the gene like a virus and cause expression?

Almost similar to Dawkins idea of memes, but he resists idea they are actual realities I think.

Live forever wrote:My thoughts too CS.
And it becomes evidence of how insane Statins are, and will continue to be
until a new understanding of the human is brought to light.
(Not to mention the whole industry.)

Might be a coincidence or intentional, but your spiral/vortex avatar seems to relate to the subject.

With regard to epigenetics, what are your thoughts on emotions/thoughts as living systems
that can actually surround the gene like a virus and cause expression?

Almost similar to Dawkins idea of memes, but he resists idea they are actual realities I think.

My avatar I think was sort of unintentional...one of those random things (maybe it looks a little like a Fibonacci ratio/Golden ratio pattern seen in nature, because galaxy spirals are just that.

Maybe you've seen those repeated experiments on thought intention on matter (ala water or something else) or how the body is is more electro-physical as opposed to biochemical. Without a doubt toxicity within the environment will inflame a state of well being. Viruses themselves seem to be misunderstood and when present naturally (not injected via vaccine) serve sometimes critical purposes, such as getting sulfur to the right places for cellular detoxification.

Epigenetics is how the environment affects the genes, which ones are turned on or off or mutated as non-functional if perturbed by a toxin.

Thoughts and emotions (for example unresolved issues) can manifest into a dis-ease and will not regress until those issues are resolved. A good example is cancer when the emotional component exacerbates the aggressive state as the immune system is left also helpless.