Pillows, Pillows, Pillows..??..

[docj077]

By the way Michael,

Seeing as how sebum production is directly stimulated by androgen action, I thought that the following study would be interesting to you. Especially, since it demonstrates that children seem to have very similar amounts of testosterone in their hair when compared to women.

J Endocrinol. 1998 Oct;159(1):R5-8. Links
The measurement of testosterone in hair.Wheeler MJ, Zhong YB, Kicman AT, Coutts SB.
Department of Chemical Pathology, Guy's and St Thomas' NHS Trust, St Thomas' Hospital, London, SE1 7EH.

Trace metals and drugs have been measured in hair for a number of years but there are no published papers on the measurement of steroids in human hair. We report here the measurement of testosterone in hair samples taken from men, women and prepubertal children. This was a preliminary investigation to see whether testosterone was detectable in hair and whether concentrations between men and women, and men and prepubertal children were different in line with concentrations of testosterone in the blood. Hair was digested in sodium hydroxide and the testosterone extracted before measurement by radioimmuno- assay. There was a clear difference between testosterone concentrations found in heir collected from men (12.9-77.7 pmol/g) and those found in hair from women (<0.9-10.8 pmol/g). There was no significant difference between the concentrations found in women and children. The authenticity of the testosterone measured was confirmed with GCMS.




Here is another important study demonstrating the change in the external hormonal environment when you compare balding scalp to non-balding scalp.

J Dermatol Sci. 2004 Feb;34(1):11-6. Links
Comparative studies on level of androgens in hair and plasma with premature male-pattern baldness.Bang HJ, Yang YJ, Lho DS, Lee WY, Sim WY, Chung BC.
Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, South Korea.

BACKGROUND: It is well known that male-pattern baldness (male pattern baldness) is not started from occipital, but frontal or scalp of head. We can assume that distribution of androgenic steroids is different for each region of the head. OBJECTIVE: We hypothesize that the levels of androgenic steroids are different not only between vertex hair with male pattern baldness and controls but also between occipital hair with male pattern baldness and controls. Moreover, we want to search for the biochemical indicator in plasma and hair sample (baldness: 22, non-baldness: 13) obtained from dermatology of medical center. After then, we desire to present fundamental data regarding diagnosis, medical cure, and prevention for premature male pattern baldness. METHODS: After hair and plasma were hydrolyzed, and then extracted with organic solvent. To assess androgenic steroids levels, we used gas chromatography-mass spectrometry (GC-MS) system in selected ion monitoring mode. RESULTS: The level of dihydrotestosterone (DHT) and the ratio of testosterone to epitestosterone (T/E ratio) in vertex hair from premature baldness subjects were higher than in the sample of non-baldness subjects (P<0.001, 0.001), whereas the levels of androgens in occipital hair from the same baldness group were not different. In addition, we discovered the levels of DHT, testosterone, and DHT/T ratio in plasma from premature male pattern baldness were higher than in those of control subjects (P<0.001, 0.001, 0.005). CONCLUSION: We verified that the distribution of androgenic steroids is unlike in various regions of individual subjects. Moreover, the increased DHT/T ratio in balding plasma indirectly confirms the high activity of 5alpha-reductase type II.



Another important study demonstrating a different phenomenon; hair follicles in men and women demonstrate different responses to hormones at the gene level.

J Investig Dermatol Symp Proc. 2005 Dec;10(3):243-6.Links
Substantial sex-dependent differences in the response of human scalp hair follicles to estrogen stimulation in vitro advocate gender-tailored management of female versus male pattern balding.Conrad F, Ohnemus U, Bodo E, Biro T, Tychsen B, Gerstmayer B, Bosio A, Schmidt-Rose T, Altgilbers S, Bettermann A, Saathoff M, Meyer W, Paus R.
Department of Dermatology, University Hospital Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.

In this study, it was investigated how estrogens (17-beta-estradiol, E2) affect the estrogen receptor (ER) expression and gene regulation of male versus female human scalp hair follicles in vitro. Anagen VI follicles from frontotemporal scalp skin were microdissected and organ-cultured for up to 9 d in the presence of E2 (1-100 nm). Immunohistochemistry was performed for ERbeta-expression, known to be predominant in human scalp hair follicles, and for TGF-beta2-expression (as negative key hair growth modulator), and E2-responsive genes in organ-cultured human scalp hair follicles (48 h, 10 nM) were explored by cDNA microarray, using a commercial skin focus chip (Memorec, Cologne, Germany). The distribution pattern of ERbeta and TGF-beta2-immunoreactivity differed between male and female hair follicles after 48 h culture. Of 1300 genes tested, several genes were regulated sex-dependent differently. The study reveals substantial sex-dependent differences in the response of frontotemporal human scalp hair follicles to E2. Recognition and systematic dissection of the E2-dependent gene regulation will be crucial for the development of more effective, gender-tailored management strategies for female versus male pattern balding.

 

[powersam]

michael barry and armando, can you please use the quote function? in some of those longer posts its hard to follow who said what.

 

[michael barry]

michael barry and armando, can you please use the quote function? in some of those longer posts its hard to follow who said what.

That thing never works for me.................LOL.




Doctor wrote:

"The level of dihydrotestosterone (DHT) and the ratio of testosterone to epitestosterone (T/E ratio) in vertex hair from premature baldness subjects were higher than in the sample of non-baldness subjects (P<0.001, 0.001), whereas the levels of androgens in occipital hair from the same baldness group were not different. In addition, we discovered the levels of DHT, testosterone, and DHT/T ratio in plasma from premature male pattern baldness were higher than in those of control subjects ("


Thats a piece of evidence as to what happens there. If you think about it, genetics would only have to have the activity of the alpha five reductase enzymes in male pattern baldness-area hair follicles be more active to overstimulate the follicle with androgen and cause baldness. If the same amount of alpha five uptick happened in occipital hair, it would probably be lost too. This could be independent of androgen receptors or magnified by androgen receptors. Its hard to believe that tissue pressure could so change the genetics of a hair follicle, that an ezyme in its root sheath would multiply and go into overdrive in response downstream, but increased hardwired genetic activity through the years seems more plausible.

 

[docj077]

michael barry and armando, can you please use the quote function? in some of those longer posts its hard to follow who said what.

That thing never works for me.................LOL.

Before you press the submit button, you need to uncheck the two boxes at the bottom of the page that deal with disabling HTML and disabling BBCode. I uncheck both of them, but I think that the only box that needs to be unchecked is the HTML box.

 

[S Foote.]

Mr. Michael Barry,

Arguing with Mr. Foote is pointless. Current research clearly demonstrates what you believe to be true. Not only does current research demonstrate an increase in androgen receptor in balding scalp, but it also demonstrates differences at the receptor level and at the gene level when you compare balding scalp to non-balding scalp follicles and scalp follicles to beard follicles.

You also miss the point.

Why is this such a hard thing for people to grasp?

We are all well aware of the studies posted here yet again. These deal with the in-vitro study of hair follicles "AFTER THE FACT". These find "differences" in follicle gene expression "AFTER" some kind of androgen related process has "ALREADY CHANGED" the follicles in-vivo! They also find differences in the status of the surroundind tissue "AFTER THE FACT"!

You are just "GUESSING" that the prior in-vivo change is a "DIRECT" action of androgens upon follicle cells!

That is just like going through the wreckage of a plane crash, finding that something doesn't work now, then blaiming the crash on that!

You offer no scientific cause and effect pathway, and you can show "NO" prior difference in gene expression in "ANY" kind of follicle before androgens become involved.

Of course gene expression and a host of other factors are changed in these "already" growth changed follicles, so what!

I will try to make this as simple as possible.

We know even high doses of androgens in-vitro do not directly change known future male pattern baldness follicles "INTO" male pattern baldness follicles, at least not immediately. As Michael said, male pattern baldness developes over time in-vivo, and shows no "direct" link with androgen levels. This can be a period of many years even as we all know.

So if you are going to claim androgens are "directly" changing normal follicles into male pattern baldness follicles, you have to explain this delay through known hormone/cell interactions.

The hormone receptor complex forms a "key" that engages with a molecular "lock" within the cells genetic material to effect a "change". The key either fits or it doesn't!

So yet again i am asking both you and Michael to explain to us all, how such a delay of many years is possible by any recognised hormone/cell interaction?

Just lets stick to this one simple point that the current direct theory "HAS" to explain to be true?

S Foote.

 

[docj077]

You really are lost, Foote. That's why I find it so pointless to even carry on conversations with you.

Too many assumptions on your part and solid scientific principles and experiments on ours. We use the interpretations of the very researchers to back our claims. I have no idea where you get your observations.

 

[S Foote.]

You really are lost, Foote. That's why I find it so pointless to even carry on conversations with you.

Too many assumptions on your part and solid scientific principles and experiments on ours. We use the interpretations of the very researchers to back our claims. I have no idea where you get your observations.

So you have no answer to my very specific question?

All you are capable of is cutting and pasting medical studies, you have no idea how to interpret these in a proper scientific way do you!

Now you are put on the spot and asked to think about the questions raised by these studies, all you can do is try to pass the responsibility on to the "researchers".

If you cannot address my point in a proper scientific manner, just butt out, and go play scientist somewhere else! :wink:

You should be ashamed of yourself coming on these forums pretending to be a Doctor when your not :roll:

S Foote.

 

[michael barry]

Im gonna try:


From Doctor's search:

"The level of dihydrotestosterone (DHT) and the ratio of testosterone to epitestosterone (T/E ratio) in vertex hair from premature baldness subjects were higher than in the sample of non-baldness subjects (P<0.001, 0.001), whereas the levels of androgens in occipital hair from the same baldness group were not different. In addition, we discovered the levels of DHT, testosterone, and DHT/T ratio in plasma from premature male pattern baldness were higher than in those of control subjects (P<0.001, 0.001, 0.005). CONCLUSION: We verified that the distribution of androgenic steroids is unlike in various regions of individual subjects. Moreover, the increased DHT/T ratio in balding plasma indirectly confirms the high activity of 5alpha-reductase type II. "



Now, .................we KNOW for a fact that men generally have more serum DHT as they age. We also KNOW that finasteride usually reduces serum DHT levels by roughly 65% on average. We also KNOW that type 2 alpha five DHT is made in your prostate and in the hair follicles all over your body.


That above experiment shows us that individual HAIR FOLLICLES in prematurely balding men have more DHT in them. Keep that in mind, more DHT in hair = baldness.


Now consider that the German researchers also find that 98.6 percent of balding men have the same variant of the androgen receptor gene, and its also pretty likely that having this variant and repeat mutations of it will increase the effect of this gene.




Now let me hypothesize and give you what I really think about baldness.

Michael Barry: Men with baldness have higher androgen receptor expression in their hair follicles and more alpha five reductase expression in the outer root sheath of their hair follicles than men who are not bald. Hairs on top of the head have been shown to have alot more DHT in them vs. occipital scalp and more DHT in them than men who dont have baldness. Balding men, close to 99% of the time have the same variant of the androgen receptor gene and have been shown to have more androgen receptors in their hair than non-balding areas of their hair or in other men who are hirsuite. ALL OF THIS MAY BE TIME DEPENDENT. KEEP THIS IN MIND. ANDROGEN RECEPTOR EXPRESSION AND ALPHA FIVE REDUCTASE ACTIVITY MIGHT INCREASE WITH AGE BY GENETIC INSTRUCTION OR IT MAY NOT. This would explain why some guys have pretty good hair at 40 and are very bald at 60. Just as we make less testsoterone as we age, we KNOW men usually make more DHT with age. Receptor-expression may increase with age to compensate for lower testosterone, but elicit a very bad result in head hair due to higher DHT.

So far this looks like there are two differences between balding men and non balding men. More androgen receptor expression and more DHT IN THE SCALP.

You know guys its not really necessary to say that hair has "flipped" its response to male hormone. Male hormone is uneccessary for head hair at all. All of the male hormone that men with their hair isn't "good" for it, but it might just grow despite it because there is not enough of it to initiate baldness. It would be very interesting to force feed the amount of male hormone that gets uptaken in a bald man's hair into a man with his hair. If the man who kept his hair had as much DHT binding as the bald man..............................THEN HE MIGHT VERY WELL GO BALD TOO GUYS. It may not be a "response" of the individuals hair, it very well may be the issue of getting enough male hormone to the hair over a long enough period of time. I know that if soaked in enough androgens, we see occipital hair cells will start to miniaturize.........................I wonder if we could really "UP" the amount of androgens in occipital hair ex vivo experiments and watch occiptial hairs (entire hairs) also begin to miniaturize. That would clear it up once and for all as far as "response" to androgens go.



Women only have a tenth of the male hormone that men do, and hence probably about a tenth of the DHT. But we KNOW that if you give them a man's level of testostoerone, they will go bald very quickly if their genetics have baldness. We have seen pictures of it, and Ive posted a study of it that showed half of the women were Norwooding after 13 years, some completely bald.



Other factors like low amounts of globulin, and hence more free testosterone, might make more androgen get uptaken and hasten the process, and an immune system that decides to go after TGF_beta overexpression or whatever it is about dying hair follicles that apparently pisses our immune systems off, will no doubt inflame the balding hairs and kill them faster........................but all of that is secondary.


The info that Doctor has been able to present leads me to believe that the combo of higher amounts of DHT made in the root sheath along with higher amounts of androgen binding due to very well-working androgen receptors are primarily what makes you go bald. Everything else is downstream of this. Another evidence in the receptor argument is an observation that Tom Hagerty has made of balding men having faces and foreheads that seem to sweat much more than hirsuite men. Ive noticed this too now that Ive looked for it. Sweat glands are androgenically stimulated and have androgen receptors. Higher receptor expresssion in the dermis is seen yet again.





The only way I can see for Stephen to prove otherwise is to find a doctor who can somehow measure pressure at the dermal papilla levels in balding scalp vs. non-balding scalp. If the latter is much lower than the former, he may have something. Kevin McElwee obviously believes that follicles secrete substances that should be able to eat through collagen and move other fluids and substances out of the way to make way for expansion, even though Stephen says this does not happen. There is really no way to test Stephen's idea other than what Ive proposed, or to get a newbie to try and use a cold pack on his head a couple of times a day and see if he has success with that alone. I can't think of another way to test it. So, we are all at impasse in my opinion as far as hashing out whether or not Stephen's theory could be proven or not. Its practically a moot point now.

 

[michael barry]

I'd like to sum up my argument for Stephen in this one sentence:



"We KNOW men usually make more DHT with age. Receptor-expression may increase with age to compensate for lower testosterone, but elicit a very bad result in head hair due to higher DHT at the same time."



That, in short, might be the most of it-----------------

 

[michael barry]

Some extra androgen receptor increasing thoughts:



Polymorphism of the Androgen Receptor Gene is Associated with Male Pattern Baldness
Justine A Ellis, Margaret Stebbing and Stephen B Harrap

Department of Physiology, The University of Melbourne, Victoria, Australia

Correspondence: Professor Stephen B. Harrap, Department of Physiology, The University of Melbourne, Victoria 3010 Australia. Email: s.harrap@physiology.unimelb.edu.au

Received 19 October 2000; Revised 28 November 2000; Accepted 28 November 2000.

Top of pageAbstract
The common heritable loss of scalp hair known as male pattern baldness or androgenetic alopecia affects up to 80% of males by age 80. A balding scalp is characterized by high levels of the potent androgen dihydrotestosterone and increased expression of the androgen receptor gene. To determine if the androgen receptor gene is associated with male pattern baldness, we compared allele frequencies of the androgen receptor gene polymorphisms (StuI restriction fragment length polymorphism and two triplet repeat polymorphisms) in cases with cosmetically significant baldness (54 young and 392 older men) and controls (107 older men) with no indication of baldness. The androgen receptor gene StuI restriction site was found in all but one (98.1%) of the 54 young bald men (p =0.0005) and in 92.3% of older balding men (p =0.000004) but in only 76.6% of nonbald men. The combination of shorter CAG and GGC triplet repeat lengths was also more prevalent in bald men (p =0.03). The ubiquity of the androgen receptor gene StuI restriction site, and higher incidence of shorter triplet repeat haplotypes in bald men suggests that these markers are very close to a functional variant that is a necessary component of the polygenic determination of male pattern baldness. Functional mutation in or near the androgen receptor gene may explain the reported high levels of expression of this gene in the balding scalp.

Keywords: alopecia, androgens, genetics


============================================
"Androgen Receptor Expression ... however, we found that AR expression not only correlated with increasing age, but also was highly significantly correlated ..."
http://www.medscape.com/viewarticle/463866_4 -


===============================================
Increase in testicular androgen receptor during sexual maturation in the rat
SW Buzek and BM Sanborn
Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston 77225.

Androgen receptor concentration was measured by exchange with 3H- dimethylnortestosterone (DMNT) in cytosol and nuclear extracts from testes of rats 15-90 days of age. Dissociation kinetics verified the necessity of an extended incubation (86 h) for maximum exchange at 4 degrees C. Nuclear androgen receptor concentration per mg DNA decreased between 15 and 25 days of age, from 375 to 146 fmol per mg DNA, then increased to 584 fmol per mg DNA at 90 days. Testicular receptor content also increased between 25 and 90 days of age. Cytosol receptor concentration patterns were similar to nuclear androgen receptor patterns. The affinity of the receptor for the ligand did not change with age (mean Kd = 0.88 nM). No significant difference in androgen receptor concentration per cell was detected between cultured peritubular cells from animals 25 and 45 days of age. Androgen receptor concentrations in freshly isolated peritubular cells could not be determined. There also was no difference in receptor concentration per cell in a Leydig cell-enriched fraction from animals between 25 and 45 days of age. Although androgen receptor concentrations per Sertoli cell increased between 15 and 35 days of age, the increase in Leydig cell number over the same period probably accounted for approximately 75% of the increase in receptor per testis between 25 and 45 days of age.


===============================================

Look at this:

Increased Androgen Receptor Expression Correlates with Development of Age-Dependent, Lobe-Specific Spontaneous Hyperplasia of the Brown Norway Rat Prostate
Partha P. Banerjee1, Subhadra Banerjee1 and Terry R. Brown
Division of Reproductive Biology, Department of Biochemistry and Molecular Biology, The Johns Hopkins University, Baltimore, Maryland 21205


Abstract
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References


Androgens are essential for development and differentiated function, as well as proliferation and survival of cells within the prostate gland. Age-related changes in the hormonal milieu, marked by a decrease in the serum androgen to estrogen ratio may contribute to the evolution of pathological changes, such as benign prostatic hyperplasia and carcinoma of the prostate gland, in older men. A similar phenomenon occurs in Brown Norway rats, in which the serum testosterone to estradiol ratio declines with age, and despite the lower serum testosterone level, age-dependent prostatic hyperplasia develops in the dorsal and lateral lobes, but not in the ventral lobe. To evaluate a role for changes in androgen action in the evolution of prostatic hyperplasia, we compared the immunostaining intensity of androgen receptor in the different prostate lobes from young (4 months of age) and old (24 months of age) Brown Norway rats. Androgen receptor immunostaining was present in the nuclei of all epithelial cells and some stromal cells throughout the prostatic ducts of each lobe from both young and old rats. Whereas androgen receptor immunostaining intensity decreased in luminal epithelial cells of the ventral prostate from old rats, it increased in luminal epithelial cells of the dorsal and lateral lobes from old rats, when compared with young rats. To validate immunocytochemical studies, Western blot analyses were performed. The total tissue level of androgen receptor decreased by 30% in the ventral lobe of old rats, whereas tissue levels of androgen receptor increased 2.7-fold and 1.3-fold in the dorsal and lateral lobes, respectively, of old rats. Similarly, the percentage of epithelial cells staining positive for the proliferation marker, proliferating cell nuclear antigen, was increased approximately 2-fold in the dorsal and lateral lobes as a function of older age. The presence of higher levels of androgen receptor and increased number of proliferating cell nuclear antigen-positive cells in the dorsal and lateral lobes of old rats suggest that changes in androgen receptor levels may be related to the lobe-specific proliferation of cells that occurs with increasing age. Additional evidence for lobe-specific regulation of androgen receptor expression was obtained from Western blots and by immunocytochemistry following castration. Androgen receptor levels in the ventral and dorsal lobes, but not the lateral lobe, of young and old rats were down-regulated in the absence of testicular androgen. However, nuclear immunostaining of androgen receptor returned by 7–10 d after castration in the ventral and dorsal lobes in the continued absence of androgen. Moreover, up-regulation of the androgen receptor level occurred more rapidly in the ventral and dorsal lobes of old, compared with young, castrated rats. Taken together, these results suggest that lobe-specific and age-dependent differences in the regulation of androgen receptor expression might lead to changes in tissue androgen responsiveness and the consequent development of lobe-specific hyperplasia in the Brown Norway rat prostate gland



" AR was associated with increased age "
http://www.medscape.com/viewarticle/463866







me again............................see what I mean. We KNOW older men have more DHT, but their androgen receptor expression in their hairs might also be elevated. I'd bet this is the big key if you want my opinion. I would really like to see what ol' Brad Pitts' hair would do if it entertained as much DHT (or was force fed it) that Michael Jordan's hair had. I would almost bet that he'd start going bald.

 

[S Foote.]

I'd like to sum up my argument for Stephen in this one sentence:



"We KNOW men usually make more DHT with age. Receptor-expression may increase with age to compensate for lower testosterone, but elicit a very bad result in head hair due to higher DHT at the same time."



That, in short, might be the most of it-----------------

Michael.

Thank you for taking the time to respond to my point properly.

However?

We all understand the current theory to revolve around the so called "genetic predisposition" of follicle cells in the male pattern baldness area, to a growth restricting action of androgens right?

It is claimed the levels of androgens in the individual are not important, but rather the genetic makeup of the cells that are responsive "TO" a particular level of androgens in the individual.

If as you claim Michael that higher local levels of DHT, along with the extra receptor expression in pre-disposed follicles are responsible for male pattern baldness, these "BOTH" exist in the in-vitro tests.

So we go back to my original point, how come when both the conditions you claim are important are there in-vitro, that known "future" male pattern baldness cells are not converted into male pattern baldness cells?

There are plenty of DHT molecules and receptors to form the right "keys" to activate the growth restricting genetics, but it just doesn't happen!

So you are back to having to explain how it is possible for such a time delay of sometimes years, in an "alledged" direct hormone/cell interaction?

S Foote.

 

[michael barry]

Stephen,


I guess Im sort of formulating my own "alternative" theory here (so everyone can take shots at me, thats fine).


What Im proposing is that many men like David Beckham just dont have enough androgen-receptors AND alpha five reductase activity IN THEIR SCALP HAIRS to really "kick off" baldness.


Example:
If you could pluck five hairs from David Beckhams frontal scalp, and measure the androgen receptors, and the amount of alpha five created........................................I have a hunch that you would find that he has much less receptor expression in his hair and much less alpha five around his hair follicles also. If we could synthetically add androgen receptors to five of his cultivated hairs in an experiment and add as much DHT as a balding guy's balding hair makes..................we might be suprised as Beckham's unreceeded hair's might react negatively to it.

I know the experiment that added a bunch of testosterone and DHT to occipital hairs was only hair CELLS, but I'd be very interested to see what ALOT of androgen (given that docs would have to "seed" the ex vivo test tube follicles in extra androgen receptors) could do with whole hairs ex vivo.


In experiments up to this point, the can give "donor" hair a bunch of male hormone in a test tube, but if he doesn't have half the androgen receptors or receptors that only work half as well (or both) than a balding man's balding area follicles, just more androgen alone might not do the trick. And in all honesty, we run into the time thing again...................it would be much better if they could run a test for a good month.



I could very well be wrong about all of that. I also conceed that some people probably have hair with more "resistance" to male hormone. But we know that they have great hair with no male hormone and do not need it to have head hair. It makes me wonder...................................

 

[Guest]

My brain hurts, but I love pillows.

 

[docj077]

[quote="michael barry":062bd]I'd like to sum up my argument for Stephen in this one sentence:



"We KNOW men usually make more DHT with age. Receptor-expression may increase with age to compensate for lower testosterone, but elicit a very bad result in head hair due to higher DHT at the same time."



That, in short, might be the most of it-----------------

So we go back to my original point, how come when both the conditions you claim are important are there in-vitro, that known "future" male pattern baldness cells are not converted into male pattern baldness cells?

.[/quote:062bd]

This statement is why I don't pay attention to you anymore. In-vitro studies HAVE demonstrated that hair follicles taken from the occipital region of men will undergo growth inhibition when increasing testosterone concentrations are used in conjunction with increasing time intervals. I already posted that study for you.

Also, you seperate "future" follicles from already balding follicles. That is scientifically incorrect as the molecular response to androgens will be the same at any age if the concentration is high enough. As soon as high potency androgens are produced in high enough concentrations in the local environment and testosterone concentration is increased by the testicles after adrenarche, the process known as androgenic alopecia will begin. The follicles are producing the defective androgen receptor from birth and as studies demonstrate a particular concentration of androgens is needed, as well as, a particular time interval of time exposure. The level of androgen production, the degree of androgen receptor and co-receptor mutation, the amount of androgen receptor produced, and the amount of locally produced five alpha reductase all impact the degree of severity when it comes to the overall androgen response.

The same process can occur in hair follicles with normal androgen receptors if the androgen receptors are over-expressed using a vector leading to a stronger hormonal signaling response. Again, there have been articles that have demonstrated this very phenonemon posted on this site.

 

[S Foote.]

Stephen,


I guess Im sort of formulating my own "alternative" theory here (so everyone can take shots at me, thats fine).


What Im proposing is that many men like David Beckham just dont have enough androgen-receptors AND alpha five reductase activity IN THEIR SCALP HAIRS to really "kick off" baldness.


Example:
If you could pluck five hairs from David Beckhams frontal scalp, and measure the androgen receptors, and the amount of alpha five created........................................I have a hunch that you would find that he has much less receptor expression in his hair and much less alpha five around his hair follicles also. If we could synthetically add androgen receptors to five of his cultivated hairs in an experiment and add as much DHT as a balding guy's balding hair makes..................we might be suprised as Beckham's unreceeded hair's might react negatively to it.

I know the experiment that added a bunch of testosterone and DHT to occipital hairs was only hair CELLS, but I'd be very interested to see what ALOT of androgen (given that docs would have to "seed" the ex vivo test tube follicles in extra androgen receptors) could do with whole hairs ex vivo.


In experiments up to this point, the can give "donor" hair a bunch of male hormone in a test tube, but if he doesn't have half the androgen receptors or receptors that only work half as well (or both) than a balding man's balding area follicles, just more androgen alone might not do the trick. And in all honesty, we run into the time thing again...................it would be much better if they could run a test for a good month.



I could very well be wrong about all of that. I also conceed that some people probably have hair with more "resistance" to male hormone. But we know that they have great hair with no male hormone and do not need it to have head hair. It makes me wonder...................................

The points you raise are valid Michael, thats why we have to be carefull about the correct context of experimental evidence.

Please refer to my post to the medical student.

S Foote.

 

[S Foote.]

http://www.ncbi.nlm.nih.gov/sites/entre ... med_docsum[/url]

If so your comments clearly show your ignorance of the context of evidence, and what or not is relevant to that context.

That crude study exposes scalp hair follicles to very high doses of androgens in-vitro. There is no reference to the receptor status in the abstract at least, and we know receptor expression is severly effected in the culturing process. Also there are no controls in that study, that would show the effect "IS" at least a function of androgen receptors and not just the toxicity of such high levels of androgens.

If the results were due to hormone/receptor/cell interaction, beard DP cells should have shown the "opposite" effect in the same experiment.

This crude "poisoning" of DP cells in-vitro tells us nothing.

The studies i refer to show the testing of balding and pre-balding DP cells, and have a known functioning receptor status.

http://www.fasebj.org/cgi/content/full/16/14/1967

Very importantly in the context of receptor status that "YOU" claim is different in balding/non-balding cells is this.

Quote:

" To rule out the possibility that androgen/AR complex in DPCs from non-bald frontal scalp has no effect on the growth of KCs due to the low expression or activity of transfected AR, we compared the expression level and transcriptional activity of AR in AR-transfected DPCs from bald and non-bald frontal scalp. Western blot analysis and reporter assays using MMTV-Luc showed that the expression level and transcriptional activity of AR were similar in AR-transfected DPCs from bald and non-bald frontal scalp (Fig. 1B ).

So you are just plain wrong in your assumptions "Doctor".

Nothing different in receptor status, nothing different in hormone levels, no "pre-disposed" difference in genetic expression in pre-balding DP's that is "turning on" male pattern baldness in these studies.

So tell me by what recognised physical mechanism is it "possible" for androgens to be "DIRECTLY CAUSING" male pattern baldness?

S Foote.

 

[docj077]

http://www.ncbi.nlm.nih.gov/sites/entre ... med_docsum[/url]

If so your comments clearly show your ignorance of the context of evidence, and what or not is relevant to that context.

That crude study exposes scalp hair follicles to very high doses of androgens in-vitro. There is no reference to the receptor status in the abstract at least, and we know receptor expression is severly effected in the culturing process. Also there are no controls in that study, that would show the effect "IS" at least a function of androgen receptors and not just the toxicity of such high levels of androgens.

If the results were due to hormone/receptor/cell interaction, beard DP cells should have shown the "opposite" effect in the same experiment.

This crude "poisoning" of DP cells in-vitro tells us nothing.



S Foote.[/quote:55dc4]

Remind me again, why you think that high doses of androgens are "poisonous" to follicular cells? Especially, since high hormone doses are usually associated with cellular hypertrophy, hyperplasia, or even immortality.

As far as I know, testosterone does not form DNA adducts or cause DNA strand breaks alone. There a very few places in the body where testosterone is cytotoxic and those areas are more affected, because testosterone is activity metabolized in those areas.

I think that the fact that the growth inhibition is dose AND time related speaks volumes. That means that not only are androgens causing growth inhibition with increasing doses, but it also means that the cells require exposure for a specific length of time in order to upregulate the cellular machinary necessary to transcribe and translate the genes necessary for growth inhibition to occur. That phenomenon is not demonstrated in what you consider to be "poisoning."

 

[Bryan]

michael barry and armando, can you please use the quote function? in some of those longer posts its hard to follow who said what.

That thing never works for me.................LOL.

I agree with Sam that it's very difficult to read and understand when you don't use the "quote" function. Let's find out what the problem is: what actually happens when you click the "Quote" button?

 

[Bryan]

We all understand the current theory to revolve around the so called "genetic predisposition" of follicle cells in the male pattern baldness area, to a growth restricting action of androgens right?

It is claimed the levels of androgens in the individual are not important, but rather the genetic makeup of the cells that are responsive "TO" a particular level of androgens in the individual.

If as you claim Michael that higher local levels of DHT, along with the extra receptor expression in pre-disposed follicles are responsible for male pattern baldness, these "BOTH" exist in the in-vitro tests.

So we go back to my original point, how come when both the conditions you claim are important are there in-vitro, that known "future" male pattern baldness cells are not converted into male pattern baldness cells?

There are plenty of DHT molecules and receptors to form the right "keys" to activate the growth restricting genetics, but it just doesn't happen!

So you are back to having to explain how it is possible for such a time delay of sometimes years, in an "alledged" direct hormone/cell interaction?

Stephen, I want to say to you here (I'm totally serious, I'm not being sarcastic at all) that I've been commiserating with you for last page or so of responses, as you've been trying to explain your objection above to both Michael and docj. For some reason or other, they just didn't get your point! But I think they do now...

The central issue, of course, which you and I have been discussing ever since that one stumptailed macaque study of Uno's was first posted, is simply what causes pre-pubertal (or even post-pubertal, for that matter) scalp hair follicles to eventually become sensitive enough to androgens that they start to go bald? As I've said many times before, nobody knows the answer to that question yet, but there's no doubt in my mind that they'll eventually figure it out. Until then, it doesn't really bother me very much. I'm not losing any sleep over it! :wink: YOU like to keep focusing on it, of course, because it gives you a little bit of ammunition (however slight) to fight the standard, accepted theory of balding.

 

[Bryan]

I think that the fact that the growth inhibition is dose AND time related speaks volumes. That means that not only are androgens causing growth inhibition with increasing doses, but it also means that the cells require exposure for a specific length of time in order to upregulate the cellular machinary necessary to transcribe and translate the genes necessary for growth inhibition to occur.

But does it seem reasonable that it could take DECADES for that to occur? I personally was in my 40's before I noticed my thinning spot.

I tend to favor the "genetic clock" theory mentioned by Whiting: there's a relatively sudden period in which scalp follicles start to become more sensitive to androgens. I wish we knew what precipitates it.