Question for Stephen Foote, with pictures for a point

[michael barry]

Wookie, thats a great question....


Its off topic here guys, but JB over at hairsite posted a South Korean study which added tricomin's polypeptide copper complex to hair cells. Results were good. Here are the particulars..........

P38 THE EFFECTS ON HAIR GROWTH OF TRIPEPTIDE-COPPER COMPLEX L-ALANINE-L-HISTIDINE-L-LYSINE-CU2+(AHK-CU) IN CULTURED HUMAN OCCIPITAL DERMAL PAPILLA CELLS
Pyo HK, Yoo HG, Choi SJ, Won CH, Chung JH, Cho KH, Eun HC, Kim KH
Department of Dermatology, Seoul National University College of Medicine, Laboratory of Cutaneous Aging & Hair Biology Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea

INTRODUCTION: Tripeptide copper complex L-Alanyl-L-histidyl-L-lysine Cu2+ (AHK-Cu) is a growth factor for many kinds of cells. AHK-Cu is also known to increase growth factors such as VEGF and FGF, and to promote wound healing. OBJECTIVE: To evaluate the effect of tripeptide copper complex L-Alanyl-L-histidyl-L-lysine Cu2+ (AHK-Cu) on hair growth. METHODS: Cultured human dermal papilla cells (DPCs) were exposed to AHK-Cu (1 x 10-9 mol/L). The cytotoxicity and proliferation of cultured human DPCs were evaluated by MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide). Annexin V-FITC staining was used for identifying apoptotic cells. We measured the expression of caspase-3, PARP (poly ADP-ribose polymerase), Bcl-2, and Bax by Western blot. We measured the length of the hair follicle in vitro organ culture. RESULTS: AHK-cu stimulated growth of DPCs. Apoptotic cells were decreased compared with control. The level of caspase-3 and PARP was decreased in AHK-cu treated group than serum-free control. In human hair follicle organ culture, the elongation of hair was increased over 155% in AHK-cu treated group. CONCLUSION: AHK-Cu seems to promote the survival of human DPCs by anti-apoptotic effects. Those results were confirmed by the decrease of the expression of caspase-3 and PARP, and by the increase of the ratio of Bcl-2/Bax. AHK-cu promotes the growth of human hair follicle and also has anti-apoptotic effects on the DPCs, which may play an important role in hair growth.


Bryan,
I dont think minoxidil can do all this, especially with dermal papilla cells. Impressive stuff man.

 

[Bryan]

I have a question about androgen receptors and the hydraulic theory of baldness:

http://www.ehrs.org/conferenceabstracts ... sawaya.htm

All scalp biopsies from patients obtained 6 months after finasteride treatment revealed intense upregulation of AR expression in comparison to pre-treatment biopsies of the same patient, whereas ERs were not affected, indicating that AR is very sensitive to the affects of 5a-R type II suppression of DHT.

:freaked: :freaked: :freaked:

How does the hydraulic theory of baldness explain this upregulation of androgen receptors due to finasteride and what part do androgen receptors play in the hydraulic/androgenic balding scenario.

It's obvious what Stephen Foote is going to say by way of explanation, isn't it? He's going to say that it's just a HUGE COINCIDENCE that human hair follicles have all this built-in apparatus having to do with androgens (like androgen receptors and numerous steroidogenic enzymes like 5a-reductase and steroid sulfatase), and that they actually respond to things like finasteride by way of the aforementioned androgen receptor upregulation, not to mention all the in vitro experiments showing growth-modulatory effects from both androgens and anti-androgens.

NOOOOOO, androgens don't REALLY have any effect on hair growth in the normal in vivo situation! Everybody knows it's just EDEMA that controls hair growth in real-life!! BWAHAHAHAHAH!!!!

Bryan

 

[Aplunk1]

Bryan, you are losing it.

 

[Old Baldy]

Guys: I'm going to repost Bryan's Dr. Sawaya study again. Read it closely and please explain to me how male pattern baldness isn't triggered by androgens?

Bryan wrote:
BTW, I'm going to post an excerpt from yet another very interesting study (and by Sawaya, too!) that clearly demonstrates a DIRECT effect of androgens and antiandrogens on human hair follicles grown in culture; what's interesting about this one is that they didn't even find it necessary to transfect extra androgen receptors into the hair follicles, thus completely negating and making moot Stephen Foote's silly objection to that other study he cited! This would be: "RU58841, a new therapeutic agent affecting androgen receptor molecular interactions in human hair follicles", M.E. Sawaya, from the book "Hair Research for the Next Millenium", 1996. I'm going to skip some of the less important stuff at the beginning, and get right to the meat of this issue:


---------------------------------------------------------------------------
[...]

The study of beard and scalp hair follicles of 6 male donors in longer term culture (up to 14 days) appears to be an interesting model. The whole follicles were mounted in a collagen matrix. The study revealed significant differences (p<0.005) when the follicles were cultured in DHT (10 nM and 100 nM) in the presence or absence of 1 uM RU58841 added, i.e.:

a) in the presence of RU58841 hair follicle growth rates were found to be increased by 23% for scalp follicles but a 16% decrease was noted in beard follicles.

b) protein, DNA and RNA polymerase II activity revealed increases in scalp (25%, 12% and 12% respectively) and respectively equivalent relative decreases in beard hair follicles.

c) thioredoxin reductase activity, a sulfhydryl-reducing enzyme important for keratin protein synthesis, increased by 16% in scalp follicles after 14 days in culture but decreased by 10% in beard hair follicles.
-----------------------------------------------------------------------------

I think the relevance of the above findings in Sawaya's study for the DIRECT effects of androgens on hair follicles is screamingly obvious, and Stephen Foote doesn't even have the luxury of screaming "FOUL!" because of any added androgen receptors; that's because there WEREN'T any!

Bryan

I just don't understand why this explanation isn't accepted. It shows that follicles are sensitive to androgens.

I know things can get slow and boring at these hairloss sites now and then. We oftentimes need things to talk about, however, this study seems to be a slam dunk IMHO.

Like Bryan said in more concise terms, the follicle has this "apparatus" for receiving and "processing" androgens. The study Bryan posted shows what this "apparatus" does when exposed to androgens. The follicle growth rate is affected in no uncertain terms IMHO.

 

[S Foote.]

Guys: I'm going to repost Bryan's Dr. Sawaya study again. Read it closely and please explain to me how male pattern baldness isn't triggered by androgens?

Bryan wrote:
BTW, I'm going to post an excerpt from yet another very interesting study (and by Sawaya, too!) that clearly demonstrates a DIRECT effect of androgens and antiandrogens on human hair follicles grown in culture; what's interesting about this one is that they didn't even find it necessary to transfect extra androgen receptors into the hair follicles, thus completely negating and making moot Stephen Foote's silly objection to that other study he cited! This would be: "RU58841, a new therapeutic agent affecting androgen receptor molecular interactions in human hair follicles", M.E. Sawaya, from the book "Hair Research for the Next Millenium", 1996. I'm going to skip some of the less important stuff at the beginning, and get right to the meat of this issue:


---------------------------------------------------------------------------
[...]

The study of beard and scalp hair follicles of 6 male donors in longer term culture (up to 14 days) appears to be an interesting model. The whole follicles were mounted in a collagen matrix. The study revealed significant differences (p<0.005) when the follicles were cultured in DHT (10 nM and 100 nM) in the presence or absence of 1 uM RU58841 added, i.e.:

a) in the presence of RU58841 hair follicle growth rates were found to be increased by 23% for scalp follicles but a 16% decrease was noted in beard follicles.

b) protein, DNA and RNA polymerase II activity revealed increases in scalp (25%, 12% and 12% respectively) and respectively equivalent relative decreases in beard hair follicles.

c) thioredoxin reductase activity, a sulfhydryl-reducing enzyme important for keratin protein synthesis, increased by 16% in scalp follicles after 14 days in culture but decreased by 10% in beard hair follicles.
-----------------------------------------------------------------------------

I think the relevance of the above findings in Sawaya's study for the DIRECT effects of androgens on hair follicles is screamingly obvious, and Stephen Foote doesn't even have the luxury of screaming "FOUL!" because of any added androgen receptors; that's because there WEREN'T any!

Bryan

I just don't understand why this explanation isn't accepted. It shows that follicles are sensitive to androgens.

I know things can get slow and boring at these hairloss sites now and then. We oftentimes need things to talk about, however, this study seems to be a slam dunk IMHO.

Like Bryan said in more concise terms, the follicle has this "apparatus" for receiving and "processing" androgens. The study Bryan posted shows what this "apparatus" does when exposed to androgens. The follicle growth rate is affected in no uncertain terms IMHO.

Two points here?

I see no specific mention of the scalp follicle type used in that study? Quote:

"The study of beard and scalp hair follicles of 6 male donors in longer term culture (up to 14 days) appears to be an interesting model. The whole follicles were mounted in a collagen matrix."

Were these the so called DHT resistant follicles from the sides and back of the head? Or were they normal terminal follicles destined to be future male pattern baldness follicles? Or were they existing male pattern baldness follicles.

We need to be very sure of the prior status of the samples used in this study, if any valid claim is going to be made that this has more significance than the "usual" in-vitro studies?

Secondly, the claim made by Bryan that this "proves" the in-vivo mechanism of male pattern baldness, is completely thrown out by a scientificaly more significant study.

This was the mouse study!

It is pointless to debate the validity of Sawaya's study, when this was disproved "anyway" in a true in-vivo model!

All Bryan can do to try to play down that mouse study, is to try to deny his "OWN" opinion when he first posted it :roll:

S Foote.

 

[S Foote.]

It's very clear that you cannot even grasp the facts reported in your own links Bryan :roll:

"YOU" posted that Minoxidil link for God's sake, did you bother to read it?

Yes. Now answer the questions I asked you.

Huh????????

So you can have a swelling of the face "and" increased hair growth!

It just means the body of fluid has shifted from around the follicles to the deeper tissue.

I'll leave it up to the individual reader to decide for himself how credible that answer is. Now answer these other two questions which you conveniently ignored before:

Do you think that they experienced less BEARD growth as a result? How does that jive with the often-reported complaints from minoxidil users of excessive BODY HAIR growth?

Sigh :roll:

The individual reader has probable read those links i posted about lipidematous scalp/alopecia, you just fail to do your research as usual.

Those articles clearly show by proper histological examination, that even "extreme" visual edema, can exist in human dermal tissue, whilst the surface tissue (around follicles) remains uneffected :roll: :roll:

Just read the studies instead of jumping to conclusions 8)

Such a situation is extremely likely with minoxidil, as this is "known" to move fluid to deeper levels! In moving fluid to the deeper levels, minoxidil is reducing pressure around follicles increasing hair growth, simple 8)

Instead of your usual distractions after i have asked "you" a question, just answer my question about that mouse study?

I already have. Several times.

Then post a link so we can all see where you explained the mouse study results without contradicting yourself, and so disqualifing your answer :wink:

While your at it, you can tell us all how Latanoprost increases hair growth, if not by the mechanism i suggest??

Some as-yet unknown mechanism, apparently. BTW, latanoprost appears to have fizzled-out as a hairgrowth stimulant.

Bryan

It's only yet unknown to you Bryan :shock:

S Foote.

 

[S Foote.]

I have a question about androgen receptors and the hydraulic theory of baldness:

http://www.ehrs.org/conferenceabstracts ... sawaya.htm

All scalp biopsies from patients obtained 6 months after finasteride treatment revealed intense upregulation of AR expression in comparison to pre-treatment biopsies of the same patient, whereas ERs were not affected, indicating that AR is very sensitive to the affects of 5a-R type II suppression of DHT.

:freaked: :freaked: :freaked:

How does the hydraulic theory of baldness explain this upregulation of androgen receptors due to finasteride and what part do androgen receptors play in the hydraulic/androgenic balding scenario.

It is a good question, and the answer is simple.

My theory also requires that DHT is produced in the dermal tissue. I am suggesting that DHT evolved primarily to increase lymphatic drainage, and that is it's important role as a male hormone.

Any substance that has evolved to increase lymphatic drainage, would have to be largely produced in the outer tissue (the dermis).

Why? Because if such a substance was mainly introduced into lymph vessels towards the core of the body, the increased vessel pumping would restric flow from the outer tissues.

This back pressure effect is what happens in male pattern baldness according to my theory.

The area's of DHT production according to Merck are quote:

"Type I 5 alpha reductase is predominant in the sebaceous glands of most regions of skin, including scalp, and liver. Type I 5 alpha reductase is responsible for approximately one third of circulating DHT.The type II 5 alpha reductase isozyme is primarily found in prostate, seminal vesicles, epididymides, and hair follicles as well as liver, and is responsible for two thirds of circulating DHT."

DHT production largely in the dermis (the biggest organ in the body), ensures an even effect on lymphatic pumping.

The upregulation process in follicles and other DHT producing structures, is natures way of trying to maintain DHT production.

But this dosen't have to mean the physical effect of DHT is designed to happen where it is produced!

Consider this?

If DHT is only going to be used where it is produced, why is there serum DHT?

This is very inefficient, and nature is not normaly so? Also, why is DHT being produced in the liver? What "direct" function is DHT doing there?

The only possible reason for DHT to be produced in the liver, is so it can be released into the circulation for some purpose.

S Foote.

 

[S Foote.]

Stephen,
Your theory is fascinating in alot of ways. Even if it were proven to be wrong on head hair growth........Im inclined to believe it still might have relevance in body hair growth as Ive contemplated the "cast-hair growth phenomena" and the effects of carrying ice on the ice pack carriers growing a good bit of back hair (dont want it there though man : ).

The Latanoprost's article's authors did have a guess on why it might work that didn't have to do with fluid volume though.........(although they may be very wrong----hell the stuff is for your eyes (wonder if Proctor will ever slip this in Proxihphen as he's found a way to stuff every growth stimulant known to man in there-----a pharmacological genius that man must be).
Anyhoo......here was "their" explanation again for those following the thread:
:.............................................. "demonstrated that minoxidil is indeed a potent activator of purified PGHS-1, by assaying oxygen consumption and prostaglandin (PG)E2 production.[21] This activation was also evidenced by increased PGE2 production by BALB/c 3T3 fibroblasts and by human dermal papilla fibroblasts in culture. These findings suggest that the mechanism behind the hair-growth-stimulating effect of minoxidil is stimulation of PGE2 synthesis. If this conclusion were the case, it would stand to reason that other, more specific, PG activators (PG analogs) might show even better results."

So, in cultures, activating prostaglandin HS-1, increases in PGE2 production increased fibroblasts and human dermal papilla fibroblasts. They are stating that minoxidil might work because it stimulates PGE2 synthesis, and therefore PG activators like Latanoprost "might show even better results". Thats there explanation for one way latanoprost might work anyway. I dont know if Bryan would agree with their suggestion.

Yet again however, you have shown a fluid-shifting subsance to increase hair growth. The list from SOD's, proanthocyanidins, minoxidil. has another member.......latanoprost. It must be frustrating not to be able to get this tested.


Stephen, I dont know if youve forgotten an earlier experimental suggestion that I had. Simply talking someone who didnt plan to do anything about his hairloss to put a strong diuretic on his scalp a couple of times a day. Like petroleum jelly and ice packs for 6-12 months. Know any balding friends at work that you could pay a little money to try this for a little monetary incentive? Just a thought. I know that putting a cast or ice on an arm increases body hair growth......It would have to be head hair. Coal tar shampoos proboably wouldnt be enough.......but that could be the shampoo to be used. Ice packs too?

Perhaps we could get one of those specially bred "androgenic" mice? Dr. Uno or even better Waseda over at hairsite might be able to swing something like that. Waseda actually responds to emails over there? ......

What you often have to consider in science, is the common factor Michael.

We hear lots of different explainations for why something effects hair growth, but the only common factor i see is the fluid "factor"

I know Des Tobin tested Minoxidil on the same kind of whole follicle cultures Sawaya used. I have currently lost the link for this, but he found Minoxidil had no "direct" effect on these follicles!

If i can find the link again i will post it.

Your testing suggestions are interesting, but as you say yourself getting people to participate is not easy.

As i said, the first principles of testing my theory are in another area than male pattern baldness, and i have to concentrate on this for now.

Regards.

S Foote.

 

[S Foote.]

Here's that link Michael:

http://www.blackwell-synergy.com/doi/ab ... alCode=exd

S Foote.

 

[Bryan]

Do you think that they experienced less BEARD growth as a result? How does that jive with the often-reported complaints from minoxidil users of excessive BODY HAIR growth?

Those articles clearly show by proper histological examination, that even "extreme" visual edema, can exist in human dermal tissue, whilst the surface tissue (around follicles) remains uneffected :roll: :roll:

Just read the studies instead of jumping to conclusions 8)

Such a situation is extremely likely with minoxidil, as this is "known" to move fluid to deeper levels! In moving fluid to the deeper levels, minoxidil is reducing pressure around follicles increasing hair growth, simple 8)

Stephen, in my dealings with you over the years, I've often had the occasion to use the term "ad hoc" when discussing your theory. Do you even KNOW what that means? If not, do a Google search on it. You'll see why I use it so often with you! :wink:

Bryan

 

[Bryan]

The upregulation process in follicles and other DHT producing structures, is natures way of trying to maintain DHT production.

OH REALLY?? :lol:

Please explain to us what the upregulation of ANDROGEN RECEPTORS within hair follicle cells (NOT the upregulation of DHT itself) has to do with "maintaining" DHT production!

Bryan

 

[michael barry]

Bryan,
Do you have any opinion of the proposed prostaglandin mechanism for growth of Latanaprost? It was suggested in the same article that this might have something to do with minoxidil's succes? Thoughts?



Its frustrating Im sure, for many interested in hair, on why we cant nail down just why minoxidil exactly works..........Ive seen "opening postassium channels", but some things that close potassium channels supposedly induce growth also. Nitric Oxide release is something aloe vera gel can do. VEGF upregulation can be done with copper peptides. Inhibiting the connective tissue sheath collagen from hardering might be a lead (L'Oreal believes that the amino taurine can help there), more blood flow, more oxygen, prostalandin, bigger microcapillaries, inhibition of collagen formation............Ive seen so much. I keep thinking with todays super sensitive scientific equipment, some of the mysteries of hair will be solved, but its as if its a fabrege' egg. More we know, more complex the precise mechanisms seem to be.

Stephen, that was an interesting link on minoxidil. Perhaps minoxidil works due to what it counteracts around the follicle.................Pickart states on his website that "it seems to be the damage around the follicle" that does a hair in. Ive never seen anyone come up with a reason precisely why proanthocyanidins might work other than anti-oxidant and anti-inflammatory (that of course might be enough). I didnt know this, but barley, hops, pine bark as well as blueberries, cranberries, grape seeds and pulp, apples, and (I think) cherries supposedly have proanthocyanidins. One of these nights Im going to Wikipedia all the old essential oils and find out just what the hell is in all that stuff......

 

[wookster]

The upregulation process in follicles and other DHT producing structures, is natures way of trying to maintain DHT production.

But this dosen't have to mean the physical effect of DHT is designed to happen where it is produced!

Consider this?

If DHT is only going to be used where it is produced, why is there serum DHT?

This is very inefficient, and nature is not normaly so? Also, why is DHT being produced in the liver? What "direct" function is DHT doing there?

The only possible reason for DHT to be produced in the liver, is so it can be released into the circulation for some purpose.

S Foote.

Yes, if DHT is responsible for BPH[benign prostate hyperplasia] then it seems to be strange that DHT can also be used to reduce prostate size:

http://jcem.endojournals.org/cgi/content/full/83/8/2749

In patients with hypogonadotropic hypogonadism, DHT gel application resulted in virilization, increased muscle mass, and improved sexual function, without an increase in prostate size (14). When administered for a mean duration of 1.8 yr to older men (55–70 yr), DHT gel led to improved sexual function and a 15 percent decrease in prostate size (17). The explanation for the decreased prostate size was based on the observation that development of benign prostate hyperplasia in dogs (BPH) requires the synergistic stimulation of prostate stromal growth by local availability of both androgen (DHT) and estrogen (E2) (18, 19, 20, 21). Because DHT application suppressed gonadotropins, resulting in decreased endogenous T and E2 secretion, administration of DHT might result in significant decrease in size of the prostate because of the absence of the synergistic effect of intraprostatic E2 and/or intraprostatic DHT formation from T. There are other data in the rat, suggesting that DHT may be less likely than T to induce prostate pathology (22).

:freaked:

Does the combination of DHT AND [aromatased]estrogen cause baldness, not just DHT alone? :freaked: :freaked: :freaked:

 

[wookster]

Does the combination of DHT AND [aromatased]estrogen cause baldness, not just DHT alone? :freaked: :freaked: :freaked:

:?

http://www2.ncsu.edu/ncsu/univ_relation ... 0/hair.htm

Estrogen-Blocking Compound Found to Cause Hair Growth

Scientists at North Carolina State University have found that an estrogen-blocking compound used in their studies has an unexpected side effect: It induces hair growth in laboratory mice by stimulating inactive hair follicles.

Treating the mice with a biologically active estrogen was found to have the opposite effect: It blocks hair growth by locking follicles into a resting mode.

The discoveries suggest estrogen plays a much more important role in hair growth than scientists previously thought -- knowledge which ultimately could lead to new, more effective hair-loss treatments for humans.

[...]

 

[wookster]

:hairy: :x :hairy:

Estrogen and ...water retention? scalp tissue edema?

http://www.ultrapms.com/pms/estrogen.htm

Estrogen also increases the level of the adrenal hormone aldosterone, which prevents the normal excretion of salt from the kidneys, adding to fluid retention. This creates edema-like symptoms of bloating, abdominal swelling, and swollen breasts

I wonder if the hydraulic theory makes any new testable predictions? :wink:

 

[wookster]

:hairy: :x :hairy:

Estrogen and ...water retention? scalp tissue edema?

http://www.ultrapms.com/pms/estrogen.htm

Estrogen also increases the level of the adrenal hormone aldosterone, which prevents the normal excretion of salt from the kidneys, adding to fluid retention. This creates edema-like symptoms of bloating, abdominal swelling, and swollen breasts

I wonder if the hydraulic theory makes any new testable predictions? :wink:

http://en.wikipedia.org/wiki/Anti-androgen

Spironolactone (Aldactone, Spiritone), a synthetic 17-spirolactone corticosteroid, which is a renal competitive aldosterone antagonist

 

[Bryan]

Does the combination of DHT AND [aromatased]estrogen cause baldness, not just DHT alone?

No. Just androgen alone.

Bryan

 

[Bryan]

Estrogen-Blocking Compound Found to Cause Hair Growth

Scientists at North Carolina State University have found that an estrogen-blocking compound used in their studies has an unexpected side effect: It induces hair growth in laboratory mice by stimulating inactive hair follicles.

Treating the mice with a biologically active estrogen was found to have the opposite effect: It blocks hair growth by locking follicles into a resting mode.

The discoveries suggest estrogen plays a much more important role in hair growth than scientists previously thought -- knowledge which ultimately could lead to new, more effective hair-loss treatments for humans.

[...]

That was in BODY HAIR, so the opposite would be the case for human scalp hair.

Bryan

 

[Armando Jose]

Bryan write:
"Anybody can come up with half-way plausible theories of what might be contributing to hair loss. The really tricky part is finding EVIDENCE in support of those theories. I don't see any EVIDENCE from you that supports your theory, Armando. "

You are right, hair biology is so complex that permit a lot of theories, but the same premise for all of us....

Have you EVIDENCE of different genetic in healthy scalp hairs?

Armando

 

[wookster]

There appears to be no detectable difference between scalp hair and body hair ...on a mouse

http://archives.cnn.com/2002/TECH/scien ... usegenome/

Mice, men share 99 percent of genes

The difference between mouse and man ... only a measley one percent?