S Foote. wrote:
The LNCaP cell line `flip' does `NOT' provide a `precedent' for your theory for a number of reasons, that have been explained to you.
>Bryan wrote
And I've explained to YOU that it's pretty clear-cut: withholding androgens from them eventually causes them to flip-flop in their response to androgens. There's no use trying to put your own "spin" on it, Stephen. It's clearly analogous to what happens with scalp hair follicles, even if we don't know the exact mechanisms of why it happens in either one of those cases.<
S Foote. wrote:
Plus you just can't have it both ways Bryan. First you try to tell us that prolonged exposure `TO' androgens is needed to cause cell growth restriction. Now you try to tell us that the direct `OPPOSITE' of androgen deprevation proves your point!
>Bryan wrote
You're being quite naive. It's not at all unusual for different tissues to have different responses to hormones. For example, you may have seen my post a couple of weeks ago over on HLH where I explained to someone that androgens UPregulate the production of androgen receptors in rat neural tissue, but they DOWNregulate them in human scalp hair follicles. Your complaint that the response to androgens (or the LACK of androgens) is different in hair follicles and LNCaP CANCER cells is beyond silly! You cannot make the simple-minded assumption that they ought to be the same, therefore if they're different, that supports your theory! The only important point here that you need to acknowledge is that prolonged exposure to androgens (or a prolonged ABSENCE of androgens) is apparently able to induce a change (SOME kind of change) in the subsequent response to those same androgens in two different kinds of tissues, for whatever reason(s).<
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But you are `entirely' missing the real point here Bryan.
The LNCap cell line experiences a flip flop reaction to androgens because they are `abnormal' cancer cells. There is again `no' precedent for `normal' cells to demonstrate this kind of `opposite' reaction to varying levels of androgens! It is the genetic changes induced by an outside influence, in this case the cancer, that makes this flip flop possible!!
What you are saying in respect of the flip flop in hair follicle cells, is that the presence of androgens is in itself CREATING genetic changes that `then' allow a flip flop in androgen response.
For your analogy with LNCap cells to be valid, exposure to androgens would have to be `inducing' the cancerous changes in these cells!! This is clearly not so, or we would `ALL' develope this kind of prostate cancer!
Don't you see the point here Bryan? It takes something other than androgens to `induce' the genetic changes necessary for cells to `flip' in their response to androgens!
I argue that prior contact inhibition in-vivo, can also `induce' the necessary genetic changes for a `flipped' in-vitro response to androgens. I use the LNCap cell example as a precedent for such a `flipped' reaction to androgens.
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S Foote. wrote:
By the way, i have asked you this before, but you have avoided the issue. Please explain the mechanisms of how the `direct theory', accounts for the recognised immunology in male pattern baldness, and the profound sweating efficiency changes?
>Bryan wrote
Can you specify exactly what you mean by the "recognized immunology" in male pattern baldness? As for the sweating changes, I've read that study you're interested in (the one on hairloss and sweating changes), and it seems like a plausible theory to me. But that doesn't really have anything to do with the "direct theory", as far as I can tell. But I'm sure YOU have your own spin on that! <
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My theory doesn't have any `spin' Bryan, it doesn't need it! What a plausible theory is supposed to do is provide a cause and effect pathway to explain `all' the observations. I will describe how my theory explains these observations, then you can give us your explaination Bryan? I'am afraid your direct theory is `required' to explain the sweating changes, as these are integral to DHT related hair growth/loss! You cant just ignore what doesn't suit!
I think by now, most people know something about the inflammation component of male pattern baldness. The timeline is that follicle miniaturization tends to be followed by an immune infiltrate in the tissue around the follicles. There is an increased immune sensitivity in the individuals balding scalp, to general irritations or allergies. Over the longer term, fibrose tissue tends to form in the balding scalp.
This fibrose tissue around and below the follicles, creates a further restriction to the normal anagen enlargement we want. I can't get the link to work at the moment, but the respected researcher Dr Uno refered to this factor in one of his papers. This factor alone is yet `another' precedent for a role of normal contact inhibition in anagen follicle size.
It has been established that androgen related hair loss/growth, also has a profound effect on the sweating efficiency of the local tissue. Where androgens reduce hair growth (male pattern baldness), there is a significant increase in the local sweating capacity. Where androgens increase hair growth (beard). there is a significant reduction in the local sweating capacity. Unlike the situation in hair follicles, there are no changes in the size of the local sweat glands, or any other physical changes in these glands.
The Hydraulic theory explains this sequence of events easily, using `ONE' primary action of DHT.
I have argued that the `major' in-vivo effect of DHT on hair growth, involves DHT related changes in the local tissue fluid pressures. These changes alter the resistence to anagen follicle enlargement through normal contact inhibition.
So according to this, increased local tissue fluid pressures = reduced hair growth, and reduced local fluid pressures = increased hair growth.
In the balding scalp the increased fluid pressure, and therefore levels, that miniaturizes follicles through contact inhibition, will `ALSO' increase immune infiltrate, sensitivity, and ultimate fibrosis. This is already recognised in tissues subject to increased fluid levels in lymphedema.
http://www.lymphoedema.org.au/index.htm
Sweat glands have no `pumping' mechanism, so they are just `bleeding' off fluid at the local tissue fluid pressure. The findings in this study, are predicted by the local fluid pressure changes of the Hydraulic theory. The theory predicts reduced sweating with increased hair growth and vice versa!!
http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
So the immunology and sweating changes in male pattern baldness, can be explained by the `SAME' fluid pressure changes according to `recognised' physiology!
The direct theory can't explain these things without adding complication. For example, the direct theory proposes a `mechanism' that directly effects cell growth, and follicle size. But there are no such changes in the sweat glands, so the direct theory needs another unrelated mechanism. Bad new's in terms of scientific validity!
Remember Bryan, we must not multiply entities unnecessarily! (Ockham's razor).
I will try to respond to the other posts tommorow, it's been a long hard day!
S Foote.
