clinical:follicle genes impact

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Different gene expression profile observed in dermal papilla cells related to androgenic alopecia by DNA macroarray analysis.

Midorikawa T, Chikazawa T, Yoshino T, Takada K, Arase S.

Biological Science Research Center, Lion Corporation, Odawara City, 100 Tajima Odawara, Kanagawa 256-0811, Japan.

BACKGROUND: Androgenic alopecia (Androgenetic Alopecia) is the most common type of baldness in men. Although etiological studies have proved that androgen is one of the causes of this symptom, the defined molecular mechanism underlying androgen-related actions remains largely unknown. OBJECTIVES: To clarify the difference in the gene expression profile of dermal papilla cells (DPCs) in skin affected by baldness. METHODS: DNA macroarray study was carried out on cultured DPCs from Androgenetic Alopecia skin comparing with DPCs from skin that is not affected by baldness. RESULTS: From DNA macroarray analysis, we observed that 107 of the 1185 analyzed genes had differing expression levels. A marked difference was observed in the decreased gene expression of BMP2 and ephrin A3 and up-regulated in NT-4 gene. In order to clarify the roles of BMP2 and ephrin A3 in the hair follicles, we examined the proliferation of hair follicle keratinocyte and expression of a hair acidic keratin gene. Both BMP2 and ephrin A3 raised the proliferation rate of the outer root sheath cells (ORSCs) and induced gene expression in acidic hair keratin 3-II. Conclusion: These results lead us to the hypothesis that both BMP2 and ephrin A3 function as hair growth promoting factors in the hair cycle

 

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note:bmp2 means bone marrow protein 2 .

 

[chewbaca]

so what des this mean?

 

[2young]

My take on it is this:

1) there are genetic differences between hair follicles that are affected by androgentic allopecia (male pattern baldness) and those that are not.

2) those two substances at the end of the article are growth factors that might make hair grow.

Correct me if I'm wrong, but couldn't this be taken as further proof of donor dominance, and good news for hair multiplication? (since the mulitplied DP cells would have the same genetics as the non-balding area)?

 

[michael barry]

The study is trying to say that bone marrow protien-3 and Ehprin A-3 have decreased expression in Male Pattern Balding follicles.

Its also stating that the NT-4 gene is Upregulated in Male pattern balding follicles.

The Bone Marrow Protien-3 and Ehprin A-3 genes are linked to outer root sheath growth in hair follicles.
So in essence, if they are not really very active in balding follicles, those same follicles root sheath production is limited somewhat. There was no explanation about the upregualted NT-4 gene and its larger presence in balding follicles and how it might explicitly express itself.

COMMENT......If the press releases just tried a wee bit harder to be in laymen's terms, alot more guys would get much more excited about this information. The conclusion is guys that they have found three genes that are definitely linked to the phenomenon of miniaturization. We strike another blow in the war....hurrah!

 

[Bryan]

There are several growth factors, hormones, cytokines, etc., which are being found to differ between normal and balding follicles. I wouldn't pop-open a bottle of champaigne every time a new one is discovered! :wink: This slow process of documenting all the molecular steps of male pattern baldness is still in its infancy...

Bryan

 

[S Foote.]

My take on it is this:

1) there are genetic differences between hair follicles that are affected by androgentic allopecia (male pattern baldness) and those that are not.

2) those two substances at the end of the article are growth factors that might make hair grow.

Correct me if I'm wrong, but couldn't this be taken as further proof of donor dominance, and good news for hair multiplication? (since the mulitplied DP cells would have the same genetics as the non-balding area)?

I don't agree for the following reason.

Prior to male pattern baldness, there is no `physical' difference between the follicles in the male pattern baldness area and the sides and back of the head. All the follicles of the scalp prior to male pattern baldness are producing normal terminal scalp hair, so there can be no real difference in the expression of growth related genes, `at that time'!!

So the change in the expression of genes in male pattern baldness follicles is `CAUSED' by some action of rising levels of androgens.

But in the in-vitro tests, direct exposure to androgens of pre-balding follicle cells, does `NOT' create any change, so the change in gene expression just has to be caused by some kind of `indirect' action of androgens in-vivo.

So i don't think the current donor dominance idea is correct, by reason of the in-vitro test results, and other points i have argued before.

S Foote.

 

[Armando Jose]

Mr. Foote;

You write:
Prior to male pattern baldness, there is no `physical' difference between the follicles in the male pattern baldness area and the sides and back of the head. All the follicles of the scalp prior to male pattern baldness are producing normal terminal scalp hair, so there can be no real difference in the expression of growth related genes, `at that time'!!

This is the point: Healthy hairs express the same genes but, in male pattern baldness hair cells express different genes, probably caused by the alopecia process.

Best regads

Armando

 

[asm]

I don't get it...

Genes are genes. They lie dormant until it is time to kill hair.

So, those taken for this test that had not hairloss may have it in future. But now everything is OK and no male pattern baldness at all. So, they show some difference in found genes, but may be these genes are wrong, because it is probably they start lose hair at certain age in future.

 

[michael barry]

New info.......

Guys, Ive read that androgens may be produced within the follicle due to the follicle being a site of steroid suflate enzymes. These enzymes might change DHEAS to DHEA within the dermal papilla because the dermal papilla is a major site of sulfate expression and the papilla could use DHEAS to produce 5-alpha DHT indicating that DHT could be PRODUCED WITHIN THE FOLLICLE.

This was at dermatologytimes.com/dermatologytimes/article/articledetail.jsp?=37468 if I type the link right (If I didnt just cuss me under your collective breaths).

New evidence also states that the miniaturization of the hair follicle could also be much more abrupt than previously thought and can occur in a single cyle and worsen rapidly.

 

[Bryan]

Re: New info.......

Guys, Ive read that androgens may be produced within the follicle due to the follicle being a site of steroid suflate enzymes.

Not steroid sulfate, but steroid sulfatase.

These enzymes might change DHEAS to DHEA within the dermal papilla because the dermal papilla is a major site of sulfate expression and the papilla could use DHEAS to produce 5-alpha DHT indicating that DHT could be PRODUCED WITHIN THE FOLLICLE.

It's ALWAYS been known that DHT is produced within the hair follicle. That's what causes balding: the presence of 5a-reductase which converts testosterone into DHT.

What you're actually referring to above is the increasing awareness that besides 5a-reductase, hair follicles also contain other enzymes which activate dormant androgens (sulfated ones), and convert weak androgens into more potent ones.

Bryan

 

[Armando Jose]

Intracrinology events in hair follicle??!!

Yes, in my opinion this could be related to asynchronous hairs in scalp, different from hair body.

Armando

 

[S Foote.]

I don't get it...

Genes are genes. They lie dormant until it is time to kill hair.

So, those taken for this test that had not hairloss may have it in future. But now everything is OK and no male pattern baldness at all. So, they show some difference in found genes, but may be these genes are wrong, because it is probably they start lose hair at certain age in future.

What people ought to recognise here , is that there is no `direct' evidence at all for any `inbuilt' genetic difference in male pattern baldness follicles compared to other scalp follicles!

This is just an assumption that the current theory needs to explain male pattern baldness. But there is no evidence or indeed `ANY' precident in known physiology for the assumptions made by the current theory!

Also, the in-vitro experiments effectively disprove this assumption.

If Follicles prone to male pattern baldness were programed differently at the genetic level, pre-balding follicles would respond to direct exposure to androgens by showing a restricted growth. But the in-vivo experiments clearly show this doesn't happen!

So clearly, the influence of androgens has to be an `indirect' and not a direct effect as the current theory `assumes'.

S Foote.

 

[elguapo]

Foote, you say

What people ought to recognise here , is that there is no `direct' evidence at all for any `inbuilt' genetic difference in male pattern baldness follicles compared to other scalp follicles!

What are you suggesting, what do you think the difference is between the male pattern baldness follicles and non-male pattern baldness follicles? You think it isn't "inbuilt", but that it changes somehow by some exterior factor?

Also, the in-vitro experiments effectively disprove this assumption.

What are the in-vitro experiments? Can you give me a link?


And here you say

If Follicles prone to male pattern baldness were programed differently at the genetic level, pre-balding follicles would respond to direct exposure to androgens by showing a restricted growth. But the in-vivo experiments clearly show this doesn't happen!

So my interpretation is, and correct me if I'm wrong, that in the in-vivo experiments, they took pre-balding follicles and exposed them to androgens, and they survived?

Second question regarding the same paragraph- you say they would respond to direct exposure to androgens. But are you keeping in mind the genetic "switch", which only occurs at a later stage in life (meaning if they are "pre-balding" follicles, perhaps it just wasn't their time to be susceptible to androgens yet)? Or are you assuming that the "switch" isn't in the follicles?

I want to understand in full what you are saying. These are the only topics on this board that interest me. I, too, am suspicious of the modern theories of male pattern baldness.

 

[S Foote.]

Foote, you say

What people ought to recognise here , is that there is no `direct' evidence at all for any `inbuilt' genetic difference in male pattern baldness follicles compared to other scalp follicles!

What are you suggesting, what do you think the difference is between the male pattern baldness follicles and non-male pattern baldness follicles? You think it isn't "inbuilt", but that it changes somehow by some exterior factor?

I don't think the `REAL' evidence supports `ANY' in-built difference in hair follicles, in the way they respond to androgens.

The in-vitro tests clearly show that a direct exposure to androgens of `ANY' hair follicle, does `NOT' change their pre-existing growth characteristics! So the `CHANGE' has to be due to some kind of in-direct action of androgens, upon the conditions the follicles are subjected to in-vivo!!

Also, the in-vitro experiments effectively disprove this assumption.

What are the in-vitro experiments? Can you give me a link?

This is the often quoted results of macaque studies.
http://endo.endojournals.org/cgi/content/full/138/1/356

And here you say
If Follicles prone to male pattern baldness were programed differently at the genetic level, pre-balding follicles would respond to direct exposure to androgens by showing a restricted growth. But the in-vivo experiments clearly show this doesn't happen!

So my interpretation is, and correct me if I'm wrong, that in the in-vivo experiments, they took pre-balding follicles and exposed them to androgens, and they survived.

I'am sorry, i meant `in-vitro' not in-vivo. But yes, when follicle cells known to be `future' male pattern baldness follicle cells were exposed to androgens in-vitro, this did not `CHANGE' them into male pattern baldness follicle cells!!

Second question regarding the same paragraph- you say they would respond to direct exposure to androgens. But are you keeping in mind the genetic "switch", which only occurs at a later stage in life (meaning if they are "pre-balding" follicles, perhaps it just wasn't their time to be susceptible to androgens yet)? Or are you assuming that the "switch" isn't in the follicles?

The `assumption' here elguapo, is the assumption of the very existence of this `mythical' genetic switch! All the actual testing shows that androgens do `NOT DIRECTLY' change the way follicles produce hair!

This idea that some kind of genetic clock is ticking away in `EACH' follicle, that given time would allow follicles to `change' the way they respond to androgens `DIRECTLY', is scientificaly ridiculous!

I want to understand in full what you are saying. These are the only topics on this board that interest me. I, too, am suspicious of the modern theories of male pattern baldness.

We all know that androgens `change' the size of follicles in different areas, and therefore the production of hair.

The in-vitro testing clearly shows that the mechanism of `change' is not a `direct' action of androgens.

It is `VERY' easy to `invent' the excuse of some kind of genetic clock in follicles, to try to justify experimental results that don't suit the current theory. But that's just bad science!!

This leaves us with some kind of `in-direct' effect of androgens in `CHANGING' the size of follicles in particular areas, and so the local hair growth.

I think there are good reasons in evolution for `in-direct' effects on hair growth, and i think the greater body of evidence supports this in androgen related hair growth as i have argued before.

S Foote.