DHT and Testosterone kills hair DIRECTLY........study

[S Foote.]

That information is straight out of my medical physiology textbook and was repeated by my medical school endrocrinology professor. In vivo studies are impossible in human beings as you can't simply take out someone hair follicle and keep it alive long enough to see a scientific result.

In vitro results are the only alternative until in vivo long term studies can be performed. The same works for drugs during each and every phase of their testing. You're looking for effects and progress, not genetic mechanisms. That's what the lab work is for.

But in this case we "DO" have significant in-vivo evidence that rules out androgen inducable TGF beta-1, as the in-vivo suppresor of male pattern baldness follicles!

TGF beta-1 induced by androgens, suppresses the growth of pre-existing male pattern baldness follicle cells in-vitro. There is no immunology going on in the test tube, so the claim is as you have stated.

You argue androgens are directly interacting with follicle cells and the TGF beta-1 pathway to suppress male pattern baldness follicle cells in-vitro, so this "must" be what is happening in-vivo!

The study below was the perfect in-vivo test of this assumption.

http://www.hairlosshelp.com/forums/mess ... &forumid=1

This study involved transplanting human male pattern baldness follicles to immuno-deficient mice. The androgen levels in those mice was normal enough to produce male and female mice, and as Bryan pointed out far lower androgen levels in humans are known to maintain miniaturised male pattern baldness follicles.

So what happened?

The human male pattern baldness follicles re-enlarged dramaticaly, in the presence of more than enough androgens to keep them miniaturised if your TGF beta-1 assumption is correct!!

So explain that?

As for the scientifc method, I've had enough of that. I did research on Enterococcus faecalis toxin-antitoxin postsegregational kill mechansims for the better duration of my masters.

With respect a doctors training is not a good grounding in science. Doctors are trained to believe the "textbook" answers. Scientists have to evaluate information in scientific terms, not just take information at face value.

A hundred years ago you would have been trained to "bleed" patients to vent noxious "vapours", and you would have believed this then "text book" fact wouldn't you! :wink:

S Foote.

 

[docj077]

Foote,

I do not think you understand the mechanism of TGF-beta's effects on the scalp.


I will give you all known effects and the sources of TGF-beta.

Sources: Platelets, T lymphocytes, macrophages, endothelial cells, keratinocytes, smooth muscle cells, and fibroblasts. Recent evidence also demonstrates that hair follicle cells are a source of TGF-beta through transcription of the TGF-beta gene by the DHT-androgen receptor complex.

Effects: Chemotactic of PMN, macrophages, lymphocytes, fibroblasts, and smooth muscle cells; stimulates TIMP synthesis, keratinocyte migration, angiogenesis, and fibroplasia; inhibits production of MMPs and keratinocyte proliferation; regulates integrin expression and other cytokines; induces TGF-beta production.

If you have an immunodeficient mouse, you don't have an immune response to the TGF-beta no matter how much androgen you produce. It doesn't matter, because no inflammation, and thus, no fibrosis of the areas surrounding the hair follicle will occur. We're talking about apoptosis of the tissues surrounding the hair follicle and fibrosis of the area afterwards with both being due to TGF-beta. The result is a hair follicle deprived of nutrients, because it doesn't get any blood. So, the epidermal stem cell populations within the hair follicle are unable to regenerate and/or produce more hair follicle cells which results in atrophy of the follicle and it eventually becoming dormant. You can give all the TGF-beta you want to the area around a follicle in a mouse with normal androgen levels. It'll cause apoptosis, but the lack of fibrosis is the key to the hair maintaining its growth. The surrounding matrix and cells will come back, because they still have the nutrients necessary to grow.

Granted, a TGF-beta inhibitor is a scary thought, bu the benefits it has on the immune system far outweighs its effects. A drug like curcumin is immunomodulatory, one of the most powerful antioxidants known to man, increases seratonin levels, and protects the brain from accumulation of beta-amyloid.

As for your lab work remark, all my lab work was done in a lab before I ever started medical school. I've done fusion PCR, northern blots, southern blots, simple electroporations, sequencing, induction of errors through Taq polymerase, and many more experiments. I know how these systems work.

We're just trying to figure this out. Don't be so cynical. It won't get us anywhere.

 

[CCS]

where do you get your curcumin with that other compound that increases its absorption? What do you think the concentration is compared to the concentrated green tea extac? Do you know if most of the GTE is good stuff or if a lot of it is random particles, since they are just water soluble?


What you just posted is interesting. Maybe our treatments prevent fibrosis, and minoxidil compensates for reduced blood flow (as one way it may work), and the CPs maybe repair the blood vessels? But it is critical to get the CPs at the right concentration. I read they can break down big colligen in scar tissue and replace it with smaller collegen like in normal skin. I wish I had some way of knowing what concentration is best, and how often.

 

[docj077]

where do you get your curcumin with that other compound that increases its absorption? What do you think the concentration is compared to the concentrated green tea extac? Do you know if most of the GTE is good stuff or if a lot of it is random particles, since they are just water soluble?


What you just posted is interesting. Maybe our treatments prevent fibrosis, and minoxidil compensates for reduced blood flow (as one way it may work), and the CPs maybe repair the blood vessels? But it is critical to get the CPs at the right concentration. I read they can break down big colligen in scar tissue and replace it with smaller collegen like in normal skin. I wish I had some way of knowing what concentration is best, and how often.

I just had the article in front of me that stated that propecia decreases TGF-Beta levels in the scalp by like 40-something percent. It's believed that this part of the downstream effects is where propecia works the best. It decreases DHT binding, which means it decrease TGF-beta by said amount in the scalp reducing the immune and cellular effects that TGF-beta has on any given individual. I'll see if I can find it again.

As for the curcumin, I just buy it at a health store in the town I live in. As for the CTE, I have no idea...sorry.

 

[docj077]

Here you go CCS,

I bolded what I thought was important.

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

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

 

[S Foote.]

Foote,

I do not think you understand the mechanism of TGF-beta's effects on the scalp.


I will give you all known effects and the sources of TGF-beta.

Sources: Platelets, T lymphocytes, macrophages, endothelial cells, keratinocytes, smooth muscle cells, and fibroblasts. Recent evidence also demonstrates that hair follicle cells are a source of TGF-beta through transcription of the TGF-beta gene by the DHT-androgen receptor complex.

Effects: Chemotactic of PMN, macrophages, lymphocytes, fibroblasts, and smooth muscle cells; stimulates TIMP synthesis, keratinocyte migration, angiogenesis, and fibroplasia; inhibits production of MMPs and keratinocyte proliferation; regulates integrin expression and other cytokines; induces TGF-beta production.

If you have an immunodeficient mouse, you don't have an immune response to the TGF-beta no matter how much androgen you produce. It doesn't matter, because no inflammation, and thus, no fibrosis of the areas surrounding the hair follicle will occur. We're talking about apoptosis of the tissues surrounding the hair follicle and fibrosis of the area afterwards with both being due to TGF-beta. The result is a hair follicle deprived of nutrients, because it doesn't get any blood. So, the epidermal stem cell populations within the hair follicle are unable to regenerate and/or produce more hair follicle cells which results in atrophy of the follicle and it eventually becoming dormant. You can give all the TGF-beta you want to the area around a follicle in a mouse with normal androgen levels. It'll cause apoptosis, but the lack of fibrosis is the key to the hair maintaining its growth. The surrounding matrix and cells will come back, because they still have the nutrients necessary to grow.

But you just cannot have it both ways!

The in-vitro testing of follicle cells, is done in the complete absense of "ANY" immunology or fibrosis, simple.

http://hairmillion.com/ref-hair-regrowt ... s3.56.html

You are trying to claim that the results in-vitro regarding androgen inducable TGF beta-1, is the mechanism of "in-vivo".

But now you try to add on a role of immune mediation???

The immune conditions in those mice "matched" those in-vitro (no immunology). But the growth effects on the male pattern baldness samples was completely opposite to the prediction if you were correct, simple.

We're just trying to figure this out. Don't be so cynical. It won't get us anywhere.

I am not being cynical i am trying to point out the flaws in your reasoning. For example you say:

" You can give all the TGF-beta you want to the area around a follicle in a mouse with normal androgen levels. It'll cause apoptosis, but the lack of fibrosis is the key to the hair maintaining its growth."

If androgens are producing TGF beta-1 in male pattern baldness follicles, they must certainly have done so in that mouse study. You claim that would cause apoptosis, but it didn't!

The follicle growth accelerated, have you even read that study?

I have had many debates with Bryan on these points, do a forum search.

S Foote.

 

[Bryan]

I'm getting a BIG kick out of this conversation. Let's just say that it gives me a certain sense of...well...déja vu!

Bryan

 

[S Foote.]

I'm getting a BIG kick out of this conversation. Let's just say that it gives me a certain sense of...well...déja vu!

Bryan

Sigh :roll:

Try and learn something this time Bryan :wink:

S Foote.

 

[docj077]

Look Foote,

Read the studies. The mechanism is scientifically proven. The effects of TGF-beta has been seen in parafollicular fibrosis with visual microscopic confirmation. I've given you the effects.

I will go through the mechanism again for you, so you understand.

The following is PROVEN:

5AR II, located on chromosome 2, creates the 5alpha reduced DHT from testosterone. Both testosterone and DHT have affinity for the androgen receptor, which is produced on the X chromosome. DHT has a higher affinity and is better able to change the confirmation of the receptor. This changes its DNA binding affinity. The androgen-receptor complex binds to the DNA and initiates transcription of the TGF-beta gene. This protein product then moves outside of the hair follicle cells where it induces apoptosis of any cell is touches through the caspase cascade. The cellular death that follows activates the immune system. Immune system activation leads to fibrosis, follicular malnutrition, and finally, atrophy of the hair follicle.

Few things are required for this response and I left out the PKC pathway, because it's unimportant for our discussion.

Every step that I've discussed with you have been proven both in vitro and in vivo. The TGF-beta pathway once it's released have been proven, because drugs that target the TGF-beta pathway are used in cancer, psoriasis, and other fibrotic disorders. The in vivo tests of this pathway are the thousands of patients that benefit from these drugs.

You can't prove the in vitro data wrong, because they use microarray, northern blotting, pcr, southern blotting, and western blotting for their data and they already know every step of the pathway. You can't prove the in vivo data wrong, because pts. get better on these drugs.

If you want a little more information, here you go. Finasteride decreases TGF-beta production by inhibiting the initial steps in the pathway. I posted an article above that proves that. Not only that, but administration of propecia increases IGF-1 production. The same hormone that grows facial hair. That has been proven IN VIVO.

Two things:
1.The entire mechanism is absolutely required for hair loss.
2.Inhibition of TGF-beta is the future of hair loss treatments.
3.I'm not going to argue with you anymore. I'm here to help people and that's what all of us working out the science is doing...helping people.

 

[Guest]

Doctor is your taking of curcumin help blocking future hair loss or regrowing?

do you take it orally? i'd love to hear more about your regimen in general

thanks

 

[S Foote.]

Look Foote,

Read the studies. The mechanism is scientifically proven. The effects of TGF-beta has been seen in parafollicular fibrosis with visual microscopic confirmation. I've given you the effects.

I will go through the mechanism again for you, so you understand.

The following is PROVEN:

5AR II, located on chromosome 2, creates the 5alpha reduced DHT from testosterone. Both testosterone and DHT have affinity for the androgen receptor, which is produced on the X chromosome. DHT has a higher affinity and is better able to change the confirmation of the receptor. This changes its DNA binding affinity. The androgen-receptor complex binds to the DNA and initiates transcription of the TGF-beta gene. This protein product then moves outside of the hair follicle cells where it induces apoptosis of any cell is touches through the caspase cascade. The cellular death that follows activates the immune system. Immune system activation leads to fibrosis, follicular malnutrition, and finally, atrophy of the hair follicle.

What "particular" studies?

Sounds very "scientific" and i am sure some people will be impressed. But you fail to describe the details of this claimed process, step by step with the proper citations??? Show us all the "proof" you claim?

People will note you have not even mentioned any mechanism for the "different" effects of androgens on follicles, the very "BASIC" issue for Gods sake :roll:

I have a few questions?

You claim:

" The androgen-receptor complex binds to the DNA and initiates transcription of the TGF-beta gene. This protein product then moves outside of the hair follicle cells where it induces apoptosis of any cell is touches through the caspase cascade."

Is this the mechanism you claim restricts male pattern baldness follicle cell growth in-vivo?

If so, that mouse study clearly refutes that notion!

Secondly, you claim follicle atrophy (miniaturisation) is an end product of the immune reaction, quote:

" Immune system activation leads to fibrosis, follicular malnutrition, and finally, atrophy of the hair follicle."

The macaque studies clearly show male pattern baldness follicle atrophy happens without any immune reaction.

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

If you want a little more information, here you go. Finasteride decreases TGF-beta production by inhibiting the initial steps in the pathway. I posted an article above that proves that. Not only that, but administration of propecia increases IGF-1 production. The same hormone that grows facial hair. That has been proven IN VIVO.

So what!

The quest is to find out how androgens cause different changes in follicles that "then" make them respond in different ways. This kind of study is "after the fact" irrelevant to that question.

You try to claim from this a direct influence of androgens in the transformation, and thats just not proven!!

Are you even aware that direct exposure to androgens does "NOT" change the pre-existing growth characteristics of hair follicles? Search the threads for the previous debates.

Two things:
1.The entire mechanism is absolutely required for hair loss.

Rubbish, the difference between the macaque and human studies proves your wrong!

2.Inhibition of TGF-beta is the future of hair loss treatments.

Rubbish, that mouse study proves you wrong! Apart from that, TGF beta-1 is required to be increased at certain stages of the normal hair cycle to ensure normal cycling.

3.I'm not going to argue with you anymore. I'm here to help people and that's what all of us working out the science is doing...helping people.

If you are really here to help people, you should do some proper research into the specifics of androgen related hair growth/loss.

Your throwing together of certain textbook information that you "think" is rellevant to male pattern baldness, does not hold up to the realities as i have pointed out and you have ignored. :wink:

Try running your arguments past Bryan :lol:

S Foote

 

[still_trying]

for us non-scientists without the time to read 16 pages of arguments (!) could someone summarise anything important that has arisen from all this please?

i saw circumin being talked about - any reason?

thanks

 

[docj077]

No, that mouse study refutes nothing. In order for TGF-beta to work it requires the immune system to induce parafollicular fibrosis. They work synergistically. Something your mouse model does not demonstrate and in fact does not even consider.

You don't read.

Are you even trying to comprehend this?

DHT binding to androgen receptor - I'm not going to site this, because it doesn't get any more obvious.


Androgen-receptor DNA binding of TGF-beta gene in vitro and subsequent gene expression -

Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth.Inui S, Fukuzato Y, Nakajima T, Yoshikawa K, Itami S.
Department of Dermatology, Course of Molecular Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.

We attempted establishing an in vitro coculture system by using human dermal papilla cells (DPCs) from androgenetic alopecia (Androgenetic Alopecia) and keratinocytes (KCs) to explore the role of androgens in hair growth regulation. Androgen showed no significant effect on the growth of KCs when they were cocultured with DPCs from Androgenetic Alopecia. Because the expressions of mRNA of androgen receptor (AR) decreased during subcultivation of DPCs in vitro, we transiently transfected the AR expression vector into the DPCs and cocultured them with KCs. In this modified coculture, androgen significantly suppressed the growth of KCs by approximately 50%, indicating that overexpression of AR can restore the responsiveness of the DPCs to androgen in vivo. We found that androgen stimulated the expression of TGF-beta1 mRNA in the cocultured DPCs. ELISA assays demonstrated that androgen treatment increased the secretion of both total and active TGF-beta1 in the conditioned medium. Moreover, the neutralizing anti-TGF-beta1 antibody reversed the androgen-elicited growth inhibition of KCs in a dose-dependent manner. These findings suggest that androgen-inducible TGF-beta1 derived from DPCs of Androgenetic Alopecia is involved in epithelial cell growth suppression in our coculture system, providing the clue to understand the paradoxical effects of androgens for human hair growth.

Role of TGF-beta2 in the human hair cycle.Hibino T, Nishiyama T.
Shiseido Life Science Research Center, 2-12-1 Fukuura, Kanazawa-ku, Yokohama 236-8643, Japan. toshihiko.hibino@to.shiseido.co.jp

Male pattern baldness is the result of premature entry into catagen due to androgens. In order to prevent hair loss, it is important to understand two critical steps, i.e., the induction mechanism of premature entry and the regression process of catagen. At the initiation, dihydrotestosterone (DHT) stimulates synthesis of transforming growth factor-beta2 (TGF-beta2) in dermal papilla cells. TGF-beta2 suppresses proliferation of epithelial cells and stimulates synthesis of certain caspases. Then TGF-beta2 triggers the intrinsic caspase network and subsequently epithelial cells are eliminated through apoptotic cell death. TGF-beta antagonists are effective in preventing catagen-like morphological changes and in promoting elongation of hair follicles in vivo and in vitro. These lines of evidence strongly suggest the presence of a "catagen cascade" in male pattern baldness, involving: (1) the conversion of testosterone to DHT by type II 5-alpha-reductase; (2) the synthesis of TGF-beta2 in dermal papilla cells; and (3) the activation of the intrinsic caspase network. These sequential events contribute to the shortening of the human hair cycle. Copyright 2004 Japanese Society for Investigative Dermatology


TGF-beta's link to fibrosis. Other articles demonstrate clear histological evidence in the hair follicle. Here's an example of the pathway in the kidney, which is exactly the same in the hair follicle-

Renal injury due to renin-angiotensin-aldosterone system activation of the transforming growth factor-beta pathway.Wolf G.
1Klinik fur Innere Medizin III, Klinikum der Friedrich-Schiller-Universitat, Jena, Germany.

Glomerulosclerosis, interstitial fibrosis, and tubular atrophy occur with end-stage kidney failure, irrespective of the primary etiology. The transforming growth factor-beta (TGF-beta) is a key factor in these alterations either directly, by stimulating synthesis of extracellular matrix components and reducing collagenase production, or indirectly through other profibrogenic factors such as connective tissue growth factor (CTGF). TGF-beta is important for the proliferation of intrarenal fibroblasts and the epithelial-mesenchymal transition through which tubular cells become fibroblasts. Although several factors induce TGF-beta expression in the kidney, one very interesting aspect is the link between the renin-angiotensin-aldosterone (Aldo) system (RAAS) and TGF-beta. Angiotensin II (ANG II) stimulates TGF-beta expression in the kidney by various mechanisms and upregulates receptors for TGF-beta. ANG II can directly phosphorylate Smads without inducing TGF-beta. Recent data provide compelling evidence that other components of the RAAS including ANG III, renin, and Aldo also activate the TGF-beta system. As direct modulation of the TGF-beta system is not yet feasible in humans, angiotensin-converting enzyme (ACE) inhibitors and angiotensin type 1 (AT(1))-receptor blockers are currently the most potential drugs to interfere with this ANG II-mediated TGF-beta expression. This review highlights some current aspects of the interaction between the RAAS and the TGF-beta axis.Kidney International advance online publication, 20 September 2006; doi:10.1038/sj.ki.5001846.



Propecia's effects on parafollicular fibrosis via TGF-beta pathway inhibition -

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

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



You should realize by now that in vitro studies are the basis for the creation of all drugs. In vivo side effects and effects are only obstained by histological evidence and preservation of live tissues with follow up DNA, RNA, and protein testing. Scientists know that increased TGF-beta in any tissue leads to fibrosis histologically. Kidneys, lungs, etc.


Now, why don't you post some studies that prove all of my studies wrong.

 

[Bryan]

for us non-scientists without the time to read 16 pages of arguments (!) could someone summarise anything important that has arisen from all this please?

Sure, I'll take care of that for you. Here's the most important summary of all that you need:

Stephen Foote should confine his efforts to the specific endeavor for which he has demonstrated a clear and obvious talent (DESIGNING AUTOMOBILE ENGINES)!

Bryan

 

[S Foote.]

No, that mouse study refutes nothing. In order for TGF-beta to work it requires the immune system to induce parafollicular fibrosis. They work synergistically. Something your mouse model does not demonstrate and in fact does not even consider.

:roll: Then how do you explain the fact that androgen inducable TGF beta-1 inhibits male pattern baldness cell growth in-vitro in the "TOTAL" absense of "ANY" immune system????

You have some serious comprehension issues!

Are you trying to claim "TWO" TGF beta-1 pathways in male pattern baldness, one in-vitro and a different one in-vivo?

You are talking absolute rubbish :roll:

Apart from that every knowledgable person reading this knows about the macaque studies i have pointed out to you!

You do not "NEED" any immunology at all for androgen related male pattern baldness!!!

This is a proven fact, and yet you just ignore this :roll:

Are you even trying to comprehend this?



Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth.Inui S, Fukuzato Y, Nakajima T, Yoshikawa K, Itami S.
Department of Dermatology, Course of Molecular Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.

We attempted establishing an in vitro coculture system by using human dermal papilla cells (DPCs) from androgenetic alopecia (Androgenetic Alopecia) and keratinocytes (KCs) to explore the role of androgens in hair growth regulation. Androgen showed no significant effect on the growth of KCs when they were cocultured with DPCs from Androgenetic Alopecia. Because the expressions of mRNA of androgen receptor (AR) decreased during subcultivation of DPCs in vitro, we transiently transfected the AR expression vector into the DPCs and cocultured them with KCs. In this modified coculture, androgen significantly suppressed the growth of KCs by approximately 50%, indicating that overexpression of AR can restore the responsiveness of the DPCs to androgen in vivo. We found that androgen stimulated the expression of TGF-beta1 mRNA in the cocultured DPCs. ELISA assays demonstrated that androgen treatment increased the secretion of both total and active TGF-beta1 in the conditioned medium. Moreover, the neutralizing anti-TGF-beta1 antibody reversed the androgen-elicited growth inhibition of KCs in a dose-dependent manner. These findings suggest that androgen-inducible TGF-beta1 derived from DPCs of Androgenetic Alopecia is involved in epithelial cell growth suppression in our coculture system, providing the clue to understand the paradoxical effects of androgens for human hair growth.

Only a complete idiot could post an in-vitro study with no immunology, in support of a claim that immunology is "needed" for those results :lol: .

I have posted hard evidence against your arguments, and i have better things to do than argue with dilusional people.

S Foote.

 

[S Foote.]

for us non-scientists without the time to read 16 pages of arguments (!) could someone summarise anything important that has arisen from all this please?

Sure, I'll take care of that for you. Here's the most important summary of all that you need:

Stephen Foote should confine his efforts to the specific endeavor for which he has demonstrated a clear and obvious talent (DESIGNING AUTOMOBILE ENGINES)!

Bryan

So you still have nothing scientific to counter my arguments with Bryan, just your usual sarcasm?

Well thats going to convince people you know something about science isn't it (not!) 8)

PS:

Have you managed to come up with any scientific justification yet for your regular posts calling my theory "ridiculous"?

You've had enough time since i last called you out on this, but still you can't back up your arogant claim!

People will reach their own conclusions Bryan :wink:

S Foote.

 

[docj077]

So, if you're saying that TGF-Beta causes hair miniaturization, then why are you arguing with me. That's what I've been saying the whole time

In the human scalp, both processes are needed. TGF-beta and deposition of materials needed for fibrosis. I've given you both of those. I don't see what the problem is. Also, I don't see why you keep confusing an inflammatory response with a cellular response through fibroblast activation. They aren't the same thing.

Scientists have seen both. Increased TGF-beta and increased fibrosis histologically.

Here's the introduction to the article I posted about parafollicular fibrosis. Now, try to disprove what is said here.

Androgenetic alopecia (Androgenetic Alopecia) is undoubtedly the most
common form of hair loss in males and androgen, especially
dihydrotestosterone (DHT) is universally accepted as a main
culprit.1) Recently, the pathogenetic role of type II 5 a reductase
(5 a-R) transforming testosterone (T) into dihydrotestosterone
(DHT) in Androgenetic Alopecia has been discovered.1,2) For that reason,
finasteride, an inhibitor of selective type II 5 a-R was introduced
as a drug and has been widely used as a promising
treatment for male pattern baldness, because it decreases
DHT levels both in serum and scalp.3,4) Nonetheless, the
exact underlying mechanisms how DHT plays a role in Androgenetic Alopecia
is not well understood.1—4)
On close histological observation of balded scalp biopsies,
the miniaturization of terminal hairs is a distinguishing feature
in Androgenetic Alopecia and is frequently associated with perifollicular
fibrosis.5,6) The miniaturization of the hair follicles was found
to be associated with a deposit of so-called “collagen or connective
tissue streamersâ€￾ beneath the follicle7) as well as a
2—2.5 times enlargement of the follicular dermal sheath
composed of densely packed collagen bundles.5) Transforming
growth factor-beta 1 (TGF- b1) has been proposed to play
an important role in catagen regulation. TGF- b1 has a negative
growth-regulatory effect on hair follicles in vitro.8)
The aim of this study was to find out the mechanisms how
androgen causes Androgenetic Alopecia in the aspect of perifollicular fibrosis
by observing the effect of T and finasteride on the expression
of type I procollagen and TGF- b1 in cultured human scalp
follicular DFs.


Results:

RESULTS
Finasteride Inhibited T-Induced Type I Procollagen
Expression in Cultured Human Scalp DFs According to
the RT-PCR analysis of target gene expression after T treatment,
hair follicular DFs from human scalp expressed type I
procollagen mRNA. A semiquantitative study clearly showed
the increased expression levels of type I procollagen in follicular
DFs in response to T treatment (Fig. 1A), which indicated
that this steroid (T) receptors are also present on DFs.
When T was treated into the culture media of DFs, T was
demonstrated to stimulate significantly type I procollagen expression
in cultured DFs (n6, p0.05). The treatment of T
of 10
8
M increased significantly type I procollagen production
up to approximately 220% in the culture media of the
scalp DFs (Fig. 1B), compared with control (100%).
In order to investigate whether finasteride (10
7
M) is involved
in T-induced type I procollagen synthesis, finasteride
was pretreated to cultured scalp DFs. The T (10
8
M) was
found to increase the transcription levels of type I a1-procollagen
up to 421.1% (p0.01), compared with the vehicletreated
control (100%). Finasteride (10
7
M) only treatment
also increased type I procollagen transcription levels upto
306.7%, compared with the vehicle treated control (100%).
However, the pre-treatment of finasteride (10
7
M) before T
(10
8
M) showed type I collagen gene transcription levels of
251.9%, compared to the vehicle-treated control (100%),
meaning that finasteride inhibited T-induced type I procollagen
transcription by 40.2% (Fig. 1C). These results suggest
that finasteride may be associated with androgen (T)-induced
mRNA expression of type I a1-procollagen in the human
scalp DFs.
Next, we performed western blot analysis for type I procollagen
protein secreted from the cultured scalp DFs under
the same condition above. The levels of type I procollagen
protein in T-treated DFs increased significantly upto 260.5%
(n5, p0.01). The expression levels of type I procollagen
protein in the finasteride/androgen co-treated scalp DFs was
significantly lower (FT, 203.5%, n5, p0.05) than those in
androgen only treated scalp DFs (Fig. 1D).
Finasteride Inhibited T-Induced TGF- b1 Expression
Levels To further investigate the molecular mechanisms of
androgen-induced type I procollagen expression, we observed
the effect of T on the expression levels of the cytokine,
TGF- b1, which are known to play an important role
in regression phase of mammalian hair cycle.9) The secreted
levels of TGF- b1 by ELISA were measured in the conditioned
media harvested at 24 h after treating DFs with T/fi-
nasteride. As shown in Fig. 2, TGF- b1 protein levels secreted
from DFs treated with T was increased about 1.82-fold in
24 h treatment, compared with those of vehicle treated control.
Pretreatment of finasteride inhibited the T-induced the
expression of TGF- b1 protein by an average of 30.4%
(p0.05).
T Increses Procollagen Expression via TGF- b1 To investigate
the regulation mechanisms of androgen-induced
type I procollagen expression via TGF- b1, we observed the
effect of T on the expression levels of type I procollagen by
TGF- b1 neutralizing antibody. The secreted levels of type I
procollagen expression were measured in the conditioned
media by treatment of T and TGF- b1 antibody. As shown in
Fig. 3, type I procollagen level on treatment of T (10
8
M)
was increased about 3.6-fold in 24 h treatment, compared
with those of vehicle treated control (p0.01). After the pretreatment
of TGF- b1 neutralizing antibody (2, 10 mg/ml),
type I procollagen expression was inhibited by an average of
12.9% and 54.3% (p0.01), respectively.



If you don't like TGF-beta as the mediator of the fibrosis, which is proved by histological examination, then find me the other molecule. I guarantee it isn't DHT.

 

[docj077]

As for you comment about the TGF-beta article, even mentioning the molecule TGF-beta automatically makes it an immune response as TGF-beta is a molecule that is part of the immune system. It doesn't matter if the response is cellular and fibroblastic, the molecule is still an immune system mediator, which I showed you earlier.

 

[S Foote.]

So, if you're saying that TGF-Beta causes hair miniaturization, then why are you arguing with me. That's what I've been saying the whole time

In the human scalp, both processes are needed. TGF-beta and deposition of materials needed for fibrosis. I've given you both of those. I don't see what the problem is. Also, I don't see why you keep confusing an inflammatory response with a cellular response through fibroblast activation. They aren't the same thing.

I am arguing with you because you are just quoting observations out of context, without any details of how these changes come about!

I also believe that the expression of TGF beta-1 is a factor in male pattern baldness, but that this happens through the process of normal contact inhibition.



I do "NOT" go along with any direct influence of androgen induced TGF beta-1 in the artificial in-vitro tests. The whole in-vitro testing of follicle cell response to androgens or anything else is totaly flawed in my opinion for many reasons.

I only refered to that observation as something that many do believe, and is refuted by that mouse study.

If you want to be taken seriously here, explain the sequence of events?

How do you explain how normal terminal follicles in the male pattern baldness area, are "converted" into male pattern baldness follicles by androgens? Be specific and provide proper references.

First do that 8)

S Foote.

 

[docj077]

As for you claim to have proven "hard evidence", you haven't posted anything that has discredited any of the studies I've posted. I explained to you why you're interpreting your study so poorly. It's not my fault you can't comprehend it.

Post a study that is relevant to what we're talking about. I've already told you that TGF is an immune system mediator and causes the development of fibrosis. Find me a study that proves ME wrong. Your murine study doesn't cut it and is really a piece of crap when it comes to our discussion.

I can grow a mouse kidney in another immunodeficient mouse and it'll grow just fine. Do the same thing in a immune competent mouse and there will be an immune response, TGF-beta release causing fibrosis of the vessels of the kidney, accumulation of immune complexes damaging the vessels even more and finally death of every cell in the kidney.

Find a study in humans that supports your claims. If you can't, then I win.