My "theory" of baldness

Topicals for hair loss
41

» » I think I hate this forum. Thats the 2nd long reply I have lost in a
» couple
» » of days. This one seemed to go through. Anyway…
»
» David thought he had a fix for the problem, but I just emailed him a while
» ago to let him know that it’s still not working…

Cool.

» » Well technically the androgen is the most upstream signal in this
» process.
» » There is nothing upstream of that as the term upstream and downstream
» is
» » used in terms of signal transduction. But now I know that you meant a
» » developmental stage that occured before the hair follicle cells had
» » committed to becoming hair follicle cells.
»
» I’m using that term more generally than just in the context of “signal
» transduction”. I’m using it to describe a whole sequence of events,
» starting with the initial reason(s) for why hair follicles first become
» either suppressed, stimulated, or stay neutral to androgens.

OK. A tricky area but yeah this is a problem/question the Follica guys are going to run into and examine before too long so I think the chances are good that we might have the beginnings of an answer and possibly an idea of how it might be controlled within a couple of years. Which is pretty good.

» » OK. But what causes one type to become one or the other has already
» been
» » and gone by the time we are here to worry about it. Causing one hair
» » follicle to change into another type of hair follicle once they have
» » diffferentiated is like getting a skin cell to change into a muscle
» cell.
» » Possible in the test tube perhaps but very tricky at the least in vivo.
»
» I’m not so sure about all that. Time will tell.

True.

» » OK. I suspect the answer wont be particularly profound though.
»
» Hey, I’m counting on that!
»
» I suspect that the simpler the explanation is, the more likely it is that
» we’ll be able to formulate the Ultimate Treatment for MPB! :slight_smile:

Indeed. It would be nice if the Gods of Hairlosss Research smiled upon us true believers for once :slight_smile:
As I mentioned one of the biggest questions around the Follica technique will be are the new hair follicles as DHT sensitive as the previous follicles in the area. If they are then I suspect they will at least begin trying to figure out why they are and if that can be changed (they seemed to figure out the pigmented/unpigmented hair thing pretty quickly). If not they may not worry about it too much. So the good news is that people should be looking into this very question. Fingers crossed.
hh

42

Bryan:
What interests me far more is what accounts for the FUNDAMENTAL DIFFERENCE between body hair follicles and scalp hair follicles which makes them respond to androgens in an OPPOSITE fashion.

I’m a bit more interested in the fundamental differences in the scalp hair follicles that are more susceptible to hair loss and the scalp hair follicles that are not. Meaning, the sides and back of the head. Body hair seems further apart in relationship to scalp hair (i.e. the characteristics are different).

What amazes me is that there’s a follicle that ceases to produce hair right next to the one that will ALWAYS produce hair. If we can identify the differences between the two, then I’d say a cure wouldn’t be too far away from that discovery. The general pattern of hair loss should be a clue (the horseshoe). Why hasn’t anyone figured out the reason for the pattern? Has there ever been a test where a follicle on the top of the head was transplanted to the side of a balding person? Did it survive?

43

» Bryan:
» What interests me far more is what accounts for the FUNDAMENTAL
» DIFFERENCE between body hair follicles and scalp hair follicles which makes
» them respond to androgens in an OPPOSITE fashion.

Maybe the problem is that scalp hair follicles in men with MBP start responding similarly] to body hair rather then oppositely.

In men with MBP scalp hair miniaturizes under the influence of DHT, so in a way it becomes more like body hair.The pattern in which this occurs is then related to genetics, just like expression of hair on the rest of your body.

44

» » Benji, thanks for the info – very interesting. I need to ponder all
» this
» » stuff. Here’s a couple more abstracts. The first one is another recent
» » genetic study which shows that a polymorphism in the ectodysplasin-A
» » receptor gene is what gives Asians thick hair. The second study shows
» that
» » ectodysplasin helps control the switch from anagen to catagen (early
» » termination of anagen – short growth cycles – are a feature of MPB).
» » Gene therapy for baldness would be really, really nice if it happens
» » someday.
» »
» » Hum Mol Genet. 2008 Mar 15;17(6):835-43.
» »
» » A scan for genetic determinants of human hair morphology: EDAR is
» » associated with Asian hair thickness.
» »
» » Department of Human Genetics, Graduate School of Medicine, The
» University
» » of Tokyo, Hongo, Tokyo, Japan.
» »
» » Hair morphology is one of the most differentiated traits among human
» » populations. However, genetic backgrounds of hair morphological
» » differences among populations have not been clarified yet. In addition,
» » little is known about the evolutionary forces that have acted on hair
» » morphology. To identify hair morphology-determining genes, the levels
» of
» » local genetic differentiation in 170 genes that are related to hair
» » morphogenesis were evaluated by using data from the International
» HapMap
» » project. Among highly differentiated genes, ectodysplasin A receptor
» » (EDAR) harboring an Asian-specific non-synonymous single nucleotide
» » polymorphism (1540T/C, 370Val/Ala) was identified as a strong
» candidate.
» » Association studies between genotypes and hair morphology revealed that
» » the Asian-specific 1540C allele is associated with increase in hair
» » thickness. Reporter gene assays suggested that 1540T/C affects the
» » activity of the downstream transcription factor NF-kappaB. It was
» inferred
» » from geographic distribution of 1540T/C and the long-range haplotype
» test
» » that 1540C arose after the divergence of Asians from Europeans and its
» » frequency has rapidly increased in East Asian populations. These
» findings
» » lead us to conclude that EDAR is a major genetic determinant of Asian
» hair
» » thickness and the 1540C allele spread through Asian populations due to
» » recent positive selection.
» »
» » PMID: 18065779 [PubMed - in process]
» »
» » Involvement of the Edar signaling in the control of hair follicle
» » involution (catagen).
» »
» » Department of Dermatology, Boston University School of Medicine, 609
» » Albany St., Boston, MA 02118, USA.
» »
» » Ectodysplasin (Eda) and its receptor (Edar) are required for normal
» » development of several ectodermal derivatives including hair follicles
» » (HFs). Here, we show that during the murine hair cycle the expression
» of
» » Eda A1, Edar, Edaradd, and TRAF6 transcripts are minimal in the resting
» » phase and maximal during HF transition from active growth to regression
» » (catagen). Eda A1 mRNA and Edar proteins were expressed in the hair
» matrix
» » and outer and inner root sheaths of anagen HFs. During catagen, Eda A1
» mRNA
» » and Edar protein were expressed in the outer and inner root sheaths and
» » later in the secondary hair germ. Catagen development accompanied by
» » increased apoptosis in the outer root sheath was significantly
» accelerated
» » in downless mice or after treatment of wild-type mice by a fusion
» protein
» » that inhibits Edar signaling, compared with the corresponding controls.
» » Microarray, real-time polymerase chain reaction, and
» immunohistochemical
» » analyses of skin of downless mice revealed a strong decrease of
» expression
» » of X-linked inhibitor of apoptosis protein (XIAP), compared with the
» » controls, suggesting XIAP as a target for Edar signaling. Thus, our
» data
» » demonstrate that in addition to its well-established role in HF
» » morphogenesis, Edar signaling is also involved in hair cycle control
» and
» » regulates apoptosis in HF keratinocytes during catagen.
» »
» » PMID: 17148670 [PubMed - indexed for MEDLINE]
»
»
»
»
» This is profoundly interesting information. Its the type of literal proof
» I’d always thought they’d be finding “someday” about how genetics directly
» controls hair thickness, hairlines, shapes of wreaths, etc. I noticed that
» the Edar signalling was implicated “involved in hair cycle control and
» » regulates apoptosis in HF keratinocytes during catagen”. Its the
» keratinocyte cell death that is intriguing to me for the reason that I
» think it just might be dead keratinocyte cells in the infidula downstream
» of DKK1, that might get the immune system interested in the follicle. If
» men with baldness lack XIAP, the “X-linked inhibitor of apoptosis protien”
» or have much less of it genetically, perhaps its why DKK-1 is so
» detrimental to our follicles over other men.
»
» What is intriguing to me personally is
» this…what could Follica do if a way to upregulate the
» “Asian-specific non-synonymous single nucleotide
» » polymorphism (1540T/C, 370Val/Ala)” or include it in their topical or
» internal after the skin-re-epilithialization period in their process
» someday, and “give” the new hair made great hair genetics no matter where
» its made.
»
»
» Ive went on and on (Im sure youve seen it) about my “inkling” that Follica
» might be able to make very good hair back in the donor area of men
» post-FUE…but might make hair that is just like MPB hair or
» might make thinner weaker hairs in MPB scalp due to all the genes that
» might be at play in the frontal scalp vs. donor scalp. Its a
» “defeatist”-kinda thought, but all the razzmatazz of promising treatments
» over the years have left me looking for ways things might fail vs. how they
» might succeed. ICX, for example (and Aderans), now honestly appear to be at
» least five years away in the best-case scenario to me now----if indeed
» within the next 10.
»
» I’ll never forget a doctor going over baldness with me when I was 25, and
» how he said “let me show you something” and he ran his finger up the side
» of my head and told me you can “feel” where you wreath is going to start
» genetically because the hair will start feeling different (weaker) at a
» certain point. It did. This was before I got on finasteride. Now the
» “change” in feeling is much more subtle, but it was pretty obvious then.
» Ive seen Washenik discuss how the skin grows up over the top of the scalp
» in fetal development and how one’s pattern seems to be determined during
» this time. It all seems so profoundly genetically hard-wired to me. Its
» amazing how genes work. I knew a family once that had a Iraqi father and a
» blonde European mother. Their four kids all looked differnt. One looked
» very Arab (and was slim), one looked like a farm boy from the midwest with
» medium brown hair (hefty), one of the girls looked like an middle eastern
» model (dark skin, dark hair and beautiful), and the other daughter was a
» very plain (some would say kinda homely) blonde gal with light skin (and
» blue eyes) that was prone to heaviness. It seemed to me that genetics was
» like a deck of cards and your chances of inheriting this or that came from
» those cards getting really mixed up and you drawing this one or that one.
» Two of those kids looked “very white” and the other to looked very Arabain.
» It was not a mix of the two as I’d expected. The blonde was very
» blonde—and the two that had black hair had JET-BLACK hair.
» Mystifying that such totality was “selected” and the two phenotypes didnt
» “mix” somewhat to produce brown hair like the hefty brother had.

you need to take a class on genetics
then you will understand more the intricacies of gene mixing

45

» Maybe the problem is that scalp hair follicles in men with MBP start
» responding similarly] to body hair rather then oppositely.
»
» In men with MBP scalp hair miniaturizes under the influence of DHT, so in
» a way it becomes more like body hair.

Huh? Are you implying that when scalp hair starts becoming thinner and shorter due to balding, they’re becoming “more like body hair” as a result?? :slight_smile:

.

46

» What amazes me is that there’s a follicle that ceases to produce hair
» right next to the one that will ALWAYS produce hair. If we can identify the
» differences between the two, then I’d say a cure wouldn’t be too far away
» from that discovery.

You got THAT right! :slight_smile:

» The general pattern of hair loss should be a clue (the horseshoe).
» Why hasn’t anyone figured out the reason for the pattern? Has
» there ever been a test where a follicle on the top of the head was
» transplanted to the side of a balding person? Did it survive?

Something even better than THAT was done: in the famous Nordstrom study, balding hair follicles from the scalp were transplanted to a subject’s arm, and they continued balding at the same rate as they did while they were still on his scalp! :wink: That pretty much settles the issue once and for all, and proves that there is something inherent to each individual hair follicle that causes balding. It disproves the various cuckoo theories about local “pressure” in the scalp skin causing balding, the old-fashioned “galea” theory, etc.

.

47

» » What amazes me is that there’s a follicle that ceases to produce hair
» » right next to the one that will ALWAYS produce hair. If we can identify
» the
» » differences between the two, then I’d say a cure wouldn’t be too far
» away
» » from that discovery.
»
» You got THAT right! :slight_smile:
»
» » The general pattern of hair loss should be a clue (the horseshoe).
» » Why hasn’t anyone figured out the reason for the pattern? Has
» » there ever been a test where a follicle on the top of the head was
» » transplanted to the side of a balding person? Did it survive?
»
» Something even better than THAT was done: in the famous Nordstrom study,
» balding hair follicles from the scalp were transplanted to a subject’s arm,
» and they continued balding at the same rate as they did while they were
» still on his scalp! :wink: That pretty much settles the issue once and for
» all, and proves that there is something inherent to each individual
» hair follicle that causes balding. It disproves the various cuckoo
» theories about local “pressure” in the scalp skin causing balding, the
» old-fashioned “galea” theory, etc.

You’d think with that information, scientists would focus more on the genetic structure of each of the two follicles rather than trying to determine what causes the follicle to die off. I know that there are some studies that claim DHT is part of the cause, but since DHT is systemic, all follicles are exposed. This leads me to believe that DHT is not bad. It’s probably needed in the system for something. :slight_smile: It’s like the sun and someone with a fair complexion. The person with the fair complexion will take more damage than the person with a darker complexion. It’s the genetic structure of the skin that matters, not the sun. :wink:

48

» You’d think with that information, scientists would focus more on the
» genetic structure of each of the two follicles rather than trying to
» determine what causes the follicle to die off. I know that there are some
» studies that claim DHT is part of the cause, but since DHT is systemic, all
» follicles are exposed. This leads me to believe that DHT is not bad.

Well, I didn’t bother to state the obvious, which is that the difference between scalp hair follicles and body hair follicles is that the former are suppressed by androgens, and the latter are stimulated by them. Scientists don’t yet understand the specific biochemical reason(s) for that, but they’re working on it as we speak.

But that IS the reason for balding: scalp follicles are damaged by androgens.

.

49

» But that IS the reason for balding: scalp follicles are damaged by
» androgens.

Not ALL scalp follicles are damages by androgens, only some. And the ones that are damaged form a specific pattern. Hmm… :wink:

50

» » But that IS the reason for balding: scalp follicles are
» » damaged by androgens.
»
» Not ALL scalp follicles are damages by androgens, only some.

The best available evidence now seems to indicate that all scalp hair follicles are damaged by androgens. Some are more damaged than others. At first glance, some don’t appear to be damaged by androgens, but they are if you raise the level high enough.

» And the ones that are damaged form a specific pattern. Hmm… :wink:

Correct. They don’t understand the reason(s) for the pattern yet, but they’re working on it.

.

51

» But there remains the little problem of explaining why it is that
» androgens stimulate the growth of (most) body hair, but
» suppress the growth of scalp hair. That does sound to me like a
» magic difference in the hair follicles’ basic characteristics! :wink:

Well of course there is a difference in scalp hair follicles as opposed to body hair follicles. In fact there appears to be a relatively large difference amongst the various hair follicles on the front and top of the scalp compared with the sides and back!

Here’s one attempt to explain a couple of things:

The androgen receptor has been shown to bind STAT proteins and in particular Stat3. Stat3 regulates growth of many stem cell populations from the gut to the brain and I would not be surprised if it regulated growth in follicular stem cells as well. When the androgen receptor is active, ie DHT is bound to it, and also bound to the activated Stat3 it can act as a repressor of many genes. This is in opposition to free Stat3, which typically turns on genes (hence the name Signal Transducer and Activator of Transcription).

When EGF binds it’s receptor it activates Stat proteins (by activating Jak2, Src, and various other proteins). So if you have a lot of active androgen receptors around and you have activated Stats then you get repression of growth. If you inhibit either pathway you get normal growth again, such as 5-alpha reductase inhibitors and EGFR inhibitors both of which have been talked about for a while now for use in hair loss. Activated Stats can induce many pro-inflammatory proteins as well, which has also been a concern in hair loss, and may be another reason why EGFR inhibitors might work. Maybe balding scalps express more of the EGF receptor than do other follicles or non-balding individuals. That said it seems as if Stat3 is particularly necessary for stem cells to remain stem cells because removal of EGF signaling can cause differentiation. Depletion of all stem cells via differentiation is no good either because you would not be able to regenerate a new follicle. So…who knows, maybe an EGFR inhibitor will be ok as long as it isn’t too potent or maybe it won’t work at all, but an androgen receptor inhibitor or 5-alpha reductase inhibitor should always be beneficial for balding scalps.

The Wnt, BMP, Notch, and SHH pathways are all also implicated very strongly in hair loss (and it is my sneaking suspicion, for reasons I have gone into in the past, that the Wnt pathway is the most important pathway to look at for regeneration of normal sized follicles).

So all in all it is extremely complicated but at least more and more research is coming out to help aid us in finding the right direction to pursue in solving the mystery of how to regenerate follicles.

52

» » But there remains the little problem of explaining why it is that
» » androgens stimulate the growth of (most) body hair, but
» » suppress the growth of scalp hair. That does sound to me like
» a
» » magic difference in the hair follicles’ basic characteristics! :wink:
»
» Well of course there is a difference in scalp hair follicles as opposed to
» body hair follicles. In fact there appears to be a relatively large
» difference amongst the various hair follicles on the front and top of the
» scalp compared with the sides and back!
»
» Here’s one attempt to explain a couple of things:
»
» The androgen receptor has been shown to bind STAT proteins and in
» particular Stat3. Stat3 regulates growth of many stem cell populations from
» the gut to the brain and I would not be surprised if it regulated growth in
» follicular stem cells as well. When the androgen receptor is active, ie DHT
» is bound to it, and also bound to the activated Stat3 it can act as a
» repressor of many genes. This is in opposition to free Stat3, which
» typically turns on genes (hence the name Signal Transducer and Activator of
» Transcription).
»
» When EGF binds it’s receptor it activates Stat proteins (by activating
» Jak2, Src, and various other proteins). So if you have a lot of active
» androgen receptors around and you have activated Stats then you get
» repression of growth. If you inhibit either pathway you get normal growth
» again, such as 5-alpha reductase inhibitors and EGFR inhibitors both of
» which have been talked about for a while now for use in hair loss.
» Activated Stats can induce many pro-inflammatory proteins as well, which
» has also been a concern in hair loss, and may be another reason why EGFR
» inhibitors might work. Maybe balding scalps express more of the EGF
» receptor than do other follicles or non-balding individuals. That said it
» seems as if Stat3 is particularly necessary for stem cells to remain stem
» cells because removal of EGF signaling can cause differentiation. Depletion
» of all stem cells via differentiation is no good either because you would
» not be able to regenerate a new follicle. So…who knows, maybe an EGFR
» inhibitor will be ok as long as it isn’t too potent or maybe it won’t work
» at all, but an androgen receptor inhibitor or 5-alpha reductase inhibitor
» should always be beneficial for balding scalps.
»
» The Wnt, BMP, Notch, and SHH pathways are all also implicated very
» strongly in hair loss (and it is my sneaking suspicion, for reasons I have
» gone into in the past, that the Wnt pathway is the most important pathway
» to look at for regeneration of normal sized follicles).
»
» So all in all it is extremely complicated but at least more and more
» research is coming out to help aid us in finding the right direction to
» pursue in solving the mystery of how to regenerate follicles.

very interesting information uwbio, thank you for posting it

53

Baldness is most common thing in males and every male want to get back his hair and for this he trying everything but he not get any change. Hair loss and hair fall is major issue in men and women. If any male suffering from baldness and want to cover his head with beautiful hairs so the new hair replacement treatment is specially for those males who are worried about their bald head and want to get back hairs on head.

54

Androgen receptor again.
What’s the cure?
DHT again
Ya da ya da yada
I’ll give you AMA theory
Genetics
But what’s the cure?
Nothing or something?