Understanding Androgenetic Alopecia

[hellouser]

The problem with this is that we know it won't work if you're already reach a certain threshold. It has already been shown that even if someone gets castrated, they will not gain their hair back. So that shows that there is some crap water fall effect that goes beyond just androgenic sensitivity

Lack of CD200 and CD34+ cells. AFAIK, nobody has tried to PROMOTE whats been downregulated in Androgenetic Alopecia. Everyone's only been trying to inhibit stuff. WHY?

 

[brunobald]

The problem with this is that we know it won't work if you're already reach a certain threshold. It has already been shown that even if someone gets castrated, they will not gain their hair back. So that shows that there is some crap water fall effect that goes beyond just androgenic sensitivity

women have pattern baldness too. Don't we all produce dht at the follicle level regardless of gender and ball status?

 

[Swoop]

Lack of CD200 and CD34+ cells. AFAIK, nobody has tried to PROMOTE whats been downregulated in Androgenetic Alopecia. Everyone's only been trying to inhibit stuff. WHY?

Reverse senescence whatever way and you have the cure. Sound so simple yet so difficult. You'll get your progenitors back that way too.

 

[hellouser]

Reverse senescence whatever way and you have the cure. Sound so simple yet so difficult. You'll get your progenitors back that way too.

You and Anteup have been doing a ton of great reading... im hoping you guys stumble on something and figure it out.

 

[Swoop]

Microarray analysis of androgenetic and senescent alopecia: Comparison of gene expression shows two distinct profiles

http://www.ncbi.nlm.....5/#!po=16.6667

The differences in gene expression profiles suggest that Androgenetic Alopecia and SA may represent two independent hair disorders and that non-androgen pathways may also contribute to hair loss. This study provides novel therapeutic targets for the prevention or treatment of two common hair disorders.​

​

That study is interesting too actually in relation to this. Let's break it up on a superficial level;

Hair/skin development and function is the most significant physiological function altered in both Androgenetic Alopecia and SA, however, the differential expressed genes in this category differed in the two diseases. Table 1 shows the 34 genes in this category that are differentially regulated in Androgenetic Alopecia that contribute to hair follicle development, morphology and cycling (BARX2, EGFR, INHBA, MSX2, OVOL1, KRTs, KRTAPs, RUNX3 and TIMP3). Many of these genes required for hair follicle homeostasis are significantly under expressed in Androgenetic Alopecia but not in SA compared to normal scalp tissue (Table 1 and Figure S1). Our data (Table 1 & Figure S1) showed that the Androgen Receptor (AR) is up regulated in Androgenetic Alopecia, but not in SA. Previous studies [4] have shown that genetic variability in AR is a prerequisite for the development of early-onset Androgenetic Alopecia. A novel Androgenetic Alopecia susceptibility locus has been identified at 17q21.31 [5]. In our dataset, the DEAD box polypeptide 5 (DDX5), a transcriptional regulator of AR [6] is down regulated in Androgenetic Alopecia and maps to this locus.

Ok this study shows that the androgen receptor in Androgenetic Alopecia is 2.46 fold changed

Whats more interesting is the bold part I underlined. A previous study has shown as you see that a suspectible locus (spot) had been identified. In this study they found a -2 fold of DDX5 which maps to this locus.

Let's take a look at DDX5 now;

http://en.wikipedia.....mid15660129-10

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is an RNA-dependent ATPase, and also a proliferation-associated nuclear antigen, specifically reacting with the simian virus 40 tumor antigen. This gene consists of 13 exons, and alternatively spliced transcripts containing several intron sequences have been detected, but no isoforms encoded by these transcripts have been identified.[1]​

With what protein does DDX5 interact? Ahh yes that's right P53; http://www.ncbi.nlm....cles/PMC548656/. Hmm isn't P53 implicated in senescence..

Let's take another gene from that study which is altered in Androgenetic Alopecia ; Aryl hydrocarbon receptor nuclear translocator-like 2 ; by -12.13 fold

Let's look it up what that thing is exactly;

The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor (AhR), and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF1). A t(1;12)(q21;p13) translocation, which results in a TEL-ARNT fusion protein, is associated with acute myeloblastic leukemia. Three alternatively spliced variants encoding different isoforms have been described for this gene.​

​

Hmm how does HIF1 relate to the hair follicle again?

Hypoxia is believed to promote an undifferentiated state in several stem and precursor cell populations (Mohyeldin et al., 2010) and our results suggest that the lower stem cell niche of human hair follicles may also be in hypoxic environment. As a portion of CD34+ stem/progenitor cells is located in this hypoxic environment and have been demonstrated to disappear during androgenetic alopecia, we hypothesized that the induction of hypoxia signaling in suboptimal conditions would help maintain hair follicle stem cell functionality and hence prevent alopecia or at least favor neogenesis. Hypoxia signaling is mediated by the hypoxia-inducible transcription factor 1 (HIF1), composed of an αβ heterodimer.​

Something with ROS/Oxidative stress.. Wasn't that a stress related signal which may lead to premature senescence..

 

[inbrugge]

Swoop, I will copy my message from BTT here as well since I believe this thread has priority for you.

What do you think about supplementations of acetyl cysteine and acetyl glutathione.

On N-acetyl cysteine:

Supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increased tumor progression and reduced survival in mouse models of B-RAF and K-RAS induced lung cancer[citation needed]. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes[citation needed]. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells[citation needed]. High levels of ROS or prolonged stress upregulates p53 and provokes a pro-oxidant response to further increase ROS, which subsequently elicits the p53-dependent apoptotic processes to eliminate damaged cells.[43][44][45] Thus, antioxidants can accelerate tumor growth by disrupting the ROS-p53 axis apoptosis, and autophagy, processes. Because somatic mutations in p53 occur late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production.[46] It is not clear what dose(s) induced these effects. Additionally, it is important to reiterate that NAC does not cause cancer, it counteracts ROS accumulation caused by p53 and down-regulates p53, which in turn prevents p53-induced apoptosis and promotes autophagy.[47] in all cells; it is a dose dependent response, and the ability to manipulate cellular apoptosis and autophagy has many therapeutic benefits.

Source: Wiki

I'm interested in taking this, but the quote above has me a little confused. If I'm not mistaken, p53 is one of the culprits of Androgenetic Alopecia. However, p53 is also a tumor repressor? I don't want to get cancer while making failed attempts to get my hair back.

 

[Armando Jose]

Microarray analysis of androgenetic and senescent alopecia: Comparison of gene expression shows two distinct profiles

http://www.ncbi.nlm.....5/#!po=16.6667

non-androgen pathways may also contribute to hair loss.


Interesting indeed

 

[Swoop]

"The consensus about what stress signal(s) after activation of the androgen receptor lead to premature senescence in Androgenetic Alopecia is not completely known. However literature points much to ROS or DNA damage or a intertwining effect of them both. This stress is to much for the cells to handle and then major pathways get activated which lead to senescence."

This is indeed a pretty big question at the moment, however if you look at the previous study we can perhaps dig a bit further into why the cells get stressed and senescence pathways like P53/pRB/P16ink4a set in. This is the study I'm talking about; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164265/

Microarray analysis of androgenetic and senescent alopecia: Comparison of gene expression shows two distinct profiles
Hair/skin development and function is the most significant physiological function altered in both Androgenetic Alopecia and SA (senescent alopecia), however, the DEGs (differentially expressed genes) in this category differed in the two diseases. Table 1 shows the 34 genes in this category that are differentially regulated in Androgenetic Alopecia that contribute to hair follicle development, morphology and cycling (BARX2, EGFR, INHBA, MSX2, OVOL1, KRTs, KRTAPs, RUNX3 and TIMP3). Many of these genes required for hair follicle homeostasis are significantly under expressed in Androgenetic Alopecia but not in SA compared to normal scalp tissue (Table 1 and Figure S1). Our data (Table 1 & Figure S1)showed that the Androgen Receptor (AR) is up regulated in Androgenetic Alopecia, but not in SA. Previous studies [4] have shown that genetic variability in AR is a prerequisite for the development of early-onset Androgenetic Alopecia. A novel Androgenetic Alopecia susceptibility locus has been identified at 17q21.31 [5]. In our dataset, the DEAD box polypeptide 5 (DDX5), a transcriptional regulator of AR [6] is down regulated in Androgenetic Alopecia and maps to this locus. The most significant pathway altered in Androgenetic Alopecia is Notch Signaling which consists of 29 genes (Table 1) including HES1, Notch2, Notch4 and PROX1 that are known to play a role in cell fate determination [7]. The down regulated genes in this pathway in Androgenetic Alopecia include CNTN1, JAG1, NOTCH2 and PSEN1 and the genes that are up regulated include DTX3, HES and NOTCH4. The expression patterns of Notch signaling pathway genes including Notch 2 and JAG1 were validated by real-time PCR (Figure S1). Jagged1 (JAG1) gene which encodes a ligand for Notch receptor maps to chromosome 20p a susceptibility locus for male-pattern baldness [8]. A reciprocal negative feedback regulation exists between Notch and AR-dependent pathways in the prostate [9]. The activation of AR and the concomitant loss of Notch signaling may be contributing factors to hair follicle miniaturization and may serve as the mechanistic link between prostate cancer and Androgenetic Alopecia. Thus, modulating the Notch signaling pathway in Androgenetic Alopecia may lead to future therapies.
This is the table with differentially expressed genes in androgenetic alopecia with changes of -2 or +2 , basically the ones that stand out the most; http://www.ncbi.nlm.nih.gov/pmc/arti...ort=objectonly

Obviously as said there is evidence again that the androgen receptor is fcked in Androgenetic Alopecia, they found a 2.46 fold increase of this compared to control as you can see in the link just above and in the picture here above where I underlined it in purple. I underlined the Aryl hydrocarbon receptor nuclear translocator-like 2 because that one is the most differentially expressed in this research paper with a fold change of -12.13. This gene encodes a protein that is a co-factor in transcriptional regulation by hypoxia-inducible factor 1 (HIF-1A). We'll come back to this later.

Now they say that the most significant pathway altered in androgenetic alopecia is NOTCH signalling which consists of 29 genes. Furthermore they refer to a other study which found a suspectibility locus for Androgenetic Alopecia at chromosome 20p, and JAGGED1 (JAG1) gene is a ligand for the NOTCH receptor and maps to this. They propose that activation of the androgen receptor leads to loss of NOTCH signalling which results in miniaturization;

In conclusion, we found that canonical Notch signaling is required for late-stage granular layer differentiation and correct filaggrin processing in the epidermis. Importantly, Notch signaling loss in hair follicle lineages leads to DNA damage response and loss of stem cell characteristics, which is possibly due to aberrant activation of bulge stem cells.

Remember DNA damage? Obviously a signal which can lead very well to senescence by pathways like P53/P16/P21 etc like described in this thread.

Nonetheless, let's dig a bit further and connect the dots a bit further ourself from the information in this study. We have;

- Altered androgen receptor 2.46 fold
- Altered Aryl hydrocarbon receptor nuclear translocator-like 2 -12.13 fold
- NOTCH signalling most significant pathway altered (29 genes)

Let's propose a hypothesis and try to connect those 3 together. First we are going to look at if NOTCH and the androgen receptor have interactions with each other as proposed;

The AR and Notch receptors play essential roles in the regulation of prostate development and homeostasis. Notch signaling initiates when receptor-bearing cells interact with Notch ligands present in neighboring cells. Notch activation causes an increase in HEY1 expression and HEY1 accumulates in the nucleus repressing AR transcriptional activity. In a reciprocal way, the activation of AR upon androgen binding downregulates the expression of Notch1 receptor and its ligand Jagged1, and upregulates Sel1L, a negative regulator of Notch.

NOTCH is also expressed abundantly in hair follicles. I underlined here evidence that the activation of AR upon androgen binding can for instance downregulate NOTCH signalling and the ligand JAGGED1 which maps to a suspectible locus in Androgenetic Alopecia. I'm not going to go to deep into this, but there are many studies which show androgen receptor interaction with NOTCH, you can look them up yourself if you want.

So yes perhaps in Androgenetic Alopecia because of an overexpressed androgen receptor there is loss of NOTCH signalling. Now we go to the second point , can NOTCH signalling be connected to the Altered Aryl hydrocarbon receptor nuclear translocator-like 2 with a -12.13 fold gene expression in Androgenetic Alopecia? As I this gene encodes a protein that is a co-factor in transcriptional regulation by hypoxia-inducible factor 1 (HIF-1A). HIF-1A is also abundantly expressed in the hair follicle.

Let's look up what HIF-1A is ;

The protein encoded by HIF1 is a bHLH - PAS transcription factor found in mammalian cells growing at low oxygen concentrations. It plays an essential role in cellular and systemic responses to hypoxia.[5] This is one of the class of hypoxia inducible factors, a family that includes Hif1a, Hif2a, and Hif3a. HIF-1 functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes, including those involved in energy metabolism, angiogenesis, apoptosis, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia.

Now what many people don't really know is that the hair follicle is in a moderately to severe hypoxia state. Yes you hear that right, the cells like a hypoxic environment in the hair follicle, they like to bath in low oxygen. Especially the connective tissue which consists of the dermal papilla's too and several stem cells/progenitors. Dermal papilla cells thrive way better under hypoxic conditions too than under normoxic conditions in cell culture. HIF-1A is a regulator which protects this hypoxia state , thus loss of HIF-1A in your hair follicle would completely shred your hair follicle because your cells wouldn't cope with a higher oxygen environment. There are several studies which show this a good short summary;

Hypoxia is believed to promote an undifferentiated state in several stem and precursor cell populations (Mohyeldin et al., 2010) and our results suggest that the lower stem cell niche of human hair follicles may also be in hypoxic environment. As a portion of CD34+ stem/progenitor cells is located in this hypoxic environment and have been demonstrated to disappear during androgenetic alopecia, we hypothesized that the induction of hypoxia signaling in suboptimal conditions would help maintain hair follicle stem cell functionality and hence prevent alopecia or at least favor neogenesis. Hypoxia signaling is mediated by the hypoxia-inducible transcription factor 1 (HIF1), composed of an αβ heterodimer. The α subunit was reported to be abundantly expressed in human hair follicles (Rosenberger et al. 2007) and is regulated in an oxygen-dependent manner through prolyl-4-hydroxylase-mediated hydroxylation, which mediates proteosomal degradation (Jaakkola et al., 2001).

So we know that androgen receptor activation can lead to loss of NOTCH signalling. Does NOTCH signalling have something in common with HIF-1a?

Jup.. It does; http://www.ncbi.nlm.nih.gov/pubmed/16256737

Hypoxia requires notch signaling to maintain the undifferentiated cell state.
In addition to controlling a switch to glycolytic metabolism and induction of erythropoiesis and angiogenesis, hypoxia promotes the undifferentiated cell state in various stem and precursor cell populations. Here, we show that the latter process requires Notch signaling. Hypoxia blocks neuronal and myogenic differentiation in a Notch-dependent manner. Hypoxia activates Notch-responsive promoters and increases expression of Notch direct downstream genes. The Notch intracellular domain interacts with HIF-1alpha, a global regulator of oxygen homeostasis, and HIF-1alpha is recruited to Notch-responsive promoters upon Notch activation under hypoxic conditions. Taken together, these data provide molecular insights into how reduced oxygen levels control the cellular differentiation status and demonstrate a role for Notch in this process.
That's right there is evidence in several studies that HIF-1A needs NOTCH signalling to maintain a hypoxia state.

So we could propose now and take this study further that there is a correlation between the 3 of them,

AR> LOSS NOTCH SIGNALLING > LOSS HIF-1A > SENESCENCE PATHWAYS

HIF-1A has major interactions with senescence and P53 etc there are many studies about this;

http://www.nature.com/jid/journal/v1...d2013113a.html

An interesting corollary to this is that within tissues, oxygen gradients often exist with stem cells residing in the most hypoxic regions (83). It is tempting to think then that these cells, which are known to be more resistant to oxidative stress as a mechanism of self-preservation (84, 85), benefit from their hypoxic environments by avoiding senescence, which would be detrimental to the regenerative capacity of the tissue.

So, perhaps loss of notch signalling due to activation of the androgen receptor leads to loss of HIF-1A in the hair follicle if this would happen, your cells would get stressed as hell (Insane ROS/oxidative stress and possibly DNA DAMAGE) and pathways related to senescence would get activated which in turn would trigger SASP again, an inflammatory response.

We are learning more and more . Just a matter of time before we get the exact picture, at least the big picture is shining through.

 

[shivers20]

I concur .

Another study;

Taken from the Follica lithium patent in order to combat follicle senescence,

[0097] Because the invention is based, in part, on the recognition of lithium's ability to mobilize stem cells that promote development of skin adnexal structures (for example, enhancing hair follicle neogenesis and regeneration), the intermittent lithium treatments or pulse lithium treatments described herein can be administered concurrently or alternating sequentially with one or more of the following treatments that prevent follicle senescence, for example, anti-oxidants such as glutathione, ascorbic acid, tocopherol, uric acid, or polyphenol antioxidants); inhibitors of reactive oxygen species (ROS) generation, such as superoxide dismutase inhibitors; stimulators of ROS breakdown, such as selenium; mTOR inhibitors, such as rapamycin; or sirtuins or activators thereof, such as resveratrol, or other SIRT1, SIRT3 activators, or nicotinamide inhibitors.

 

[Python]

I am hoping something good comes of this

 

[benjt]

Impressive work, Swoop! Really good job!

 

[Armando Jose]

Another part of this uzzle, great job Swoop...

In my modest opinion I think that senecescent processes are present in the hair cycle, I remember how many times talking about the DEAD hair,

 

[S Foote.]

With respect.

People here are going through the wreckage of a plane crash, and noticing that a lot of the aircrafts characteristics are now different. None of this is relevant to the process of change, or necessarily the cause of the crash.

Does anyone want to explain how these different androgen receptors responsible for male pattern baldness, reverse their downstream effects on the follicle when transplanted into immune-deficient mice?

 

[abcdefg]

Yeah he knows his stuff but I still feel the major problems come in when you try to actually figure out what concrete substances actually accomplish all this stuff or even where in the process do you try to intervene? Coming up with a concrete product that puts information into action is by far the slowest and most important part. Its been 20 years of theory since propecia and there are still the same 2 products despite all that. So clearly a lot of things that sound promising or make sense lead to dead ends or minimal results.
With how complex it all is I doubt more and more they will ever really cure male pattern baldness aside from growing hair and just side stepping the whole problem a few decades from now

 

[Swoop]

Thanks guys

With respect.

People here are going through the wreckage of a plane crash, and noticing that a lot of the aircrafts characteristics are now different. None of this is relevant to the process of change, or necessarily the cause of the crash.

Does anyone want to explain how these different androgen receptors responsible for male pattern baldness, reverse their downstream effects on the follicle when transplanted into immune-deficient mice?

With all due respect to you S. Foote but we ain't applying philosophy here. I'm delivering a consensus to the people here not a theory. If you want to believe in your pseudo-science story then that's fine. After all some people still tend to believe bloodflow is the problem or inflammation etc. , whatever makes you happy man.

- - - Updated - - -

Yeah he knows his stuff but I still feel the major problems come in when you try to actually figure out what concrete substances actually accomplish all this stuff or even where in the process do you try to intervene? Coming up with a concrete product that puts information into action is by far the slowest and most important part. Its been 20 years of theory since propecia and there are still the same 2 products despite all that. So clearly a lot of things that sound promising or make sense lead to dead ends or minimal results.
With how complex it all is I doubt more and more they will ever really cure male pattern baldness aside from growing hair and just side stepping the whole problem a few decades from now

You want a practical intervention. I explain the big picture of the mechanism behind androgenetic alopecia. This is important because if you understand something you can narrow your therapeutic interventions. We still don't know the exact picture of androgenetic alopecia, but we are getting closer and closer. I am just laying the consensus down from latest research papers and academics working on this. Indeed Androgenetic Alopecia is incredibly hard to reverse, ultimately genetic engineering or a cell based therapy would be a way out. Nonetheless I'll make a post soon about possible current and future practical interventions and how they apply to this all. Cheers.

 

[S Foote.]

Thanks guys



With all due respect to you S. Foote but we ain't applying philosophy here. I'm delivering a consensus to the people here not a theory. If you want to believe in your pseudo-science story then that's fine. After all some people still tend to believe bloodflow is the problem or inflammation etc. , whatever makes you happy man..

I think you really need to study the scientific method, and learn what pseudo science actually is. I have no problem with any of the data you present, but as seems the norm on hair loss forums it is what is left out that really matters.

The simple bottom line is that the actual in-vivo experience proves that the data you present here, is just not relevant in the control of follicle size.

I think that anyone who really cares about better treatments for male pattern baldness, should realise that one recent study is far and away the most important male pattern baldness study so far. This is the immuno-mouse study i have referred to before.

http://www.jaad.org/article/S0190-9622(02)61499-9/pdf

Lets consider this in-vivo study of human scalp follicles in more detail. The relevant details are all in the abstract quote:

"Human hair follicles were grafted onto 2 strains of immunodeficient mice to compare the regeneration potential of vellus (miniaturized, balding) and terminal (hairy, nonbalding) follicles from males and a female exhibiting pattern baldness. Each mouse had transplants of both types of follicles from a single donor for direct comparison. Grafted follicles from 2 male donors resulted in nonsignificant differences in mean length (52 mm vs 54 mm) and mean diameter (99 μm vs 93 μm) at 22 weeks for hairs originating from balding and hairy scalp, respectively, corresponding to 400% versus 62% of the mean pretransplantation diameters. Follicles from the female donor transplanted to several mice also resulted in nonsignificant differences in length (43 mm vs 37 mm) for hairs from balding and hairy scalp, respectively, during a period of 22 weeks. The mean diameter of the originally vellus hairs increased 3-fold, whereas the terminal hairs plateaued at approximately 50% of pretransplantation diameter,"

What is of upmost importance here is the fact that "ALL" the follicle samples changed their size. male pattern baldness, large terminal, and female samples all adjusted to the same size within very close limits.

The full study makes it clear that there were more than enough androgens present, to maintain the male pattern baldness follicles if the action was mediated within the follicle. The full terminal follicles used are not regarded as androgen dependent anyway, yet importantly they to significantly increased in size.

What this study clearly demonstrates is that all the follicles were size adjusted to equality, by an external factor that is not directly androgen mediated.

If you follow the scientific rule of parsimony, there is only one genuine scientific explanation for these results.

All the follicles are enlarging to the maximum size allowed by the external resistance factor of the mouse tissue. The lack of the usual formation of a fibrotic restriction around transplanted follicles in these mice, allows this natural size adjustment.

Any other attempt to fully explain these results, would get thrown out on the grounds of parsimony in this study alone. This would not even include all the other related factors, that external resistance can explain.

 

[LayZ]

I really care about better male pattern baldness treatments.
Contrary to your beliefs, I don't think a one off research paper from 2002 done in vivo using mice is the most important work in the field.
1. Mice regen/remodel quickly including the specialized structures in skin, humans don't.
2. Not paying thirty bucks to discuss the contents of the full paper with you.
3. Do it in vivo in human skin as it seems just about anything, short of killing it, done to a mouse grows freaking hair.

 

[hellouser]

I really care about better male pattern baldness treatments.
Contrary to your beliefs, I don't think a one off research paper from 2002 done in vivo using mice is the most important work in the field.
1. Mice regen/remodel quickly including the specialed structures in skin, humans don't.
2. Not paying thirty bucks to discuss the contents of the full paper with you.
3. Do it in vivo in human skin as it seems just about anything, short of killing it, done to a mouse grows freaking hair.

Essentially, single case studies need to be done... but they NEVER are.

 

[LayZ]

10 guys getting transplants could have a graft of vellous hair moved to the forearm, plenty of dht in that environment. Get a pretty good idea if further investigation is warranted from that.

I'd let a Doctor do a punch graft on me just to see what happens, even though I'd bet against it working. And I would bet heavy in this case...

 

[Swoop]

I think you really need to study the scientific method, and learn what pseudo science actually is. I have no problem with any of the data you present, but as seems the norm on hair loss forums it is what is left out that really matters.

The simple bottom line is that the actual in-vivo experience proves that the data you present here, is just not relevant in the control of follicle size.

I think that anyone who really cares about better treatments for male pattern baldness, should realise that one recent study is far and away the most important male pattern baldness study so far. This is the immuno-mouse study i have referred to before.

http://www.jaad.org/article/S0190-9622(02)61499-9/pdf

Lets consider this in-vivo study of human scalp follicles in more detail. The relevant details are all in the abstract quote:

"Human hair follicles were grafted onto 2 strains of immunodeficient mice to compare the regeneration potential of vellus (miniaturized, balding) and terminal (hairy, nonbalding) follicles from males and a female exhibiting pattern baldness. Each mouse had transplants of both types of follicles from a single donor for direct comparison. Grafted follicles from 2 male donors resulted in nonsignificant differences in mean length (52 mm vs 54 mm) and mean diameter (99 μm vs 93 μm) at 22 weeks for hairs originating from balding and hairy scalp, respectively, corresponding to 400% versus 62% of the mean pretransplantation diameters. Follicles from the female donor transplanted to several mice also resulted in nonsignificant differences in length (43 mm vs 37 mm) for hairs from balding and hairy scalp, respectively, during a period of 22 weeks. The mean diameter of the originally vellus hairs increased 3-fold, whereas the terminal hairs plateaued at approximately 50% of pretransplantation diameter,"

What is of upmost importance here is the fact that "ALL" the follicle samples changed their size. male pattern baldness, large terminal, and female samples all adjusted to the same size within very close limits.

The full study makes it clear that there were more than enough androgens present, to maintain the male pattern baldness follicles if the action was mediated within the follicle. The full terminal follicles used are not regarded as androgen dependent anyway, yet importantly they to significantly increased in size.

What this study clearly demonstrates is that all the follicles were size adjusted to equality, by an external factor that is not directly androgen mediated.

If you follow the scientific rule of parsimony, there is only one genuine scientific explanation for these results.

All the follicles are enlarging to the maximum size allowed by the external resistance factor of the mouse tissue. The lack of the usual formation of a fibrotic restriction around transplanted follicles in these mice, allows this natural size adjustment.

Any other attempt to fully explain these results, would get thrown out on the grounds of parsimony in this study alone. This would not even include all the other related factors, that external resistance can explain.

So you are convinced by a mouse study.. First let me tell you that in humans in vivo this approach doesn't work. It doesn't mind where you will take your miniaturized hair follicle and transplant it on your ***, hand, back or chest. It won't magically regrow. We ain't mice S. Foote. Anyway lets break that study up a bit;

1. If you have read that study you know that Van Neste contradicts this study (1.)
2.

Although this study is difficult to evaluate relative to our data because of its shorter duration and the lack of information regarding pretransplantation diameters, it suggests that the males of some strains of mice have systemic androgen levels high enough and/or the grafts retain sufficient 5-R activity to impede the growth of androgen-sensitive hair follicles.

3. The most important one by far;

Therefore, the existence of an inhibitor factor other than androgens. This could be some other steroid, hormone, cytokine, neuropeptide, or an immunologically related factor.

They might for instance have an excellent autophagy or macrophage system or something else that makes this possible. If we were the same as mice we would be happy inducing de-novo morphogenesis of hair follicles currently through wounding. But hey we ain't mice.

The process starts in Androgenetic Alopecia when androgens bind to the androgen receptors in the dermal papilla cells. Everything what happens "before" that process is irrelevant to the pathology of Androgenetic Alopecia, simple as that.




1.Van Neste D. The use of scalp grafts onto nude mice as a
model for human hair growth: is there something new for
hair growth drug screen programs? In: Maibach HI, editor.
Dermatologic research techniques. Boca Raton (FL): CRC
Press; 1996. p. 37-49.