Age, DHT levels, prevalence of balding and oxidative stress

[tino]

citation from the study

"We were unable to identify androgen-responsive elements in the TGF-1 promoter. TGF-1 promoter activation by androgen is bald frontal DPC specific and is not observed in non-bald frontal DPC, suggesting that some intrinsic factor(s) in bald frontal DPC are required (data not shown). Factor(s) that are genetically involved in Androgenetic Alopecia would be the true target of the pathomechanism of the disease. Our modified co-culture system will provide clues to further explore the role of androgens in the regulation of hair growth."

Do they mean factors before tgf-beta induces his destroying work?

They are referring to the factor or factors which cause a difference in the RESPONSE of a given hair follicle to androgens (specifically in this case, whether or not TGF-1 is released in response to androgens).

I think it is clear so far that Androgenes induces a growth inhibiting tgf-beta signal in some genetic praedisposed scalp hair follicles,and a ? induced igf-1 modulated growth promoting signal in bearth and body hair follicles.I have no direct proove,but im very sure that tgf-beta downregulates the igf-1 and or his rececptors,which can crosstalk with insulin in male pattern baldness sensitive scalp hair follicles.I dont understand why this investigators did not also investigated if tgf-beta induces igf-1 deprivation or igf-1/insulin receptor downregulation.The missing signal,could be in the skin Redox Network,at least in the case of growth inhibition,but also in the case of growth promoting.A good working redox network,promotes growth(amongst others i allude to facts which says that the daily intake of vitamin c,correlats whith higher serum igf-1),and a not so good working redox network leads to growth inhibition.A naturally protection mechanism,if the system sees that there is a cancer promoting redox imbalance,it trys to downregulate everything what promotes growth.Still a big mystery are the thoughts of the nature.Why the scalp skin?And basically why the frontal and vertex scalp,and not the occiptal parts?To my theory,that the system negelected to protect hair in the case of unfavourable genetic,during which the system has to protect vital parts in the first line,suits not the fact,that hair follicles beyond the frontal and occiptal scalp,were also not worth to keep in metabolic activity.Frontal and especially vertex scalp,is mostly exposed to sunlight.Sunlight can induce skin cancer-mostly in pheomalnin caucasian individuals(Skin cancer in individuals of African, Asian, Latin-American, and American-Indian descent: differences in incidence, clinical presentation, and survival compared to Caucasians).male pattern baldness is also mostly common in caucasians and rare common in eumelain asians or africans(Current understanding of androgenetic alopecia. Part II: clinical aspects and treatment).ROS and TGF-beta have a role in skin cancer.UV Rays can upregulate TGF-beta,which acts as a tumor surpressor(http://www.nature.com/jid/journal/v119/ ... 1580a.html.).Maybe the evolution regulated a long time ago,that populations who are very sensitive to skin cancer,express more TGF-beta in high metabolic active skin parts,which are mostly sun exposed.The AR Polymorphism could just be an unfortunate trigger,which interacts casual(maybe over ROS) whith the evoulutionaery volitional TGF-beta-tumor surpressing genetic in sun exposed scalp parts.

 

[tino]

citation from the study above

Androgen receptors were detected in beard, axillary, and frontal scalp DPC, but not in DPC of androgen-independent occipital scalp hair follicles

there is a conflict whith the work below.The investigators there have found Androgenreceptors in occiptal scalp regions.

http://www.nature.com/jid/journal/v109/ ... 10071a.pdf

 

[tino]

Tino,

Here are pictures of a guy going bald from ages 15-18.

I doubt he has had time for oxidants to play a signifigant role anywhere in his dermis, but he's frontally now. Take a look,

viewtopic.php?f=11&t=41898

Yes i saw the pictures.And what does that proove?That more ROS will be upregulated,because more sebaceus gland activity in the frontal dermis,has metabolized more Testosterone to DHT,what made the frontal part sensitive as first and stronger?

 

[Bryan]

citation from the study above

Androgen receptors were detected in beard, axillary, and frontal scalp DPC, but not in DPC of androgen-independent occipital scalp hair follicles

there is a conflict whith the work below.The investigators there have found Androgenreceptors in occiptal scalp regions.

http://www.nature.com/jid/journal/v109/ ... 10071a.pdf

It's also contradicted by Whiting in his review article "Male Pattern Balding: Current Understanding", where he clearly states that ALL human scalp hair follicles contain androgen receptors. That shouldn't be particularly surprising, because there have been several such contradictory findings in studies like these. It would appear that as yet, this area of biology isn't quite an exact science!

 

[michael barry]

Tino wrote:

Still a big mystery are the thoughts of the nature.Why the scalp skin?And basically why the frontal and vertex scalp,and not the occiptal parts?To my theory,that the system negelected to protect hair in the case of unfavourable genetic,during which the system has to protect vital parts in the first line,suits not the fact,that hair follicles beyond the frontal and occiptal scalp,were also not worth to keep in metabolic activity.Frontal and especially vertex scalp,is mostly exposed to sunlight.Sunlight can induce skin cancer-mostly in pheomalnin caucasian individuals(Skin cancer in individuals of African, Asian, Latin-American, and American-Indian descent: differences in incidence, clinical presentation, and survival compared to Caucasians).male pattern baldness is also mostly common in caucasians and rare common in eumelain asians or africans(Current understanding of androgenetic alopecia

Tino,

We have had discussions for years on this website about how exactly selection made men bald in some areas of the earth with more regularity than others. Here is a review for you to consider, and as you do, you will probably come to the conclusion that we did: namely that it doesn't matter much.


Fact: Caucasians bald more than Asians
Fact: Africans bald more than Asians
Fact: Eskimos bald less than anyone

See the logical rut this leads into? Eskimos rarely bald at all, and have been "up north" for at least 5,000 years that anthropologists have determined. ALOT of East Africans in Somalia and Ethiopia go bald. If the sun is good for hair, why do so few Eskimos and Mongolians bald vs. Middle Eastern men who bald pretty regularily (depsite the fact that other Middle Eastern men appear to have some of the thickest hair on the planet?


Lets move to apes. Japanese Snow monkeys rarely bald. Other kinds of primates based near the equator bald ALOT, some almost always. Their is a lemur that always has blue eyes despite dwelling in equatorial parts of the earth. It makes no sense, but there it is.



Balding might have presented a "maturity" in evolution, or perhaps in the distant past, our ancestors lived such short violent lives, the males didn't need hair for too many years because most died off anyway while killing food and dragging it home. Who knows? We have argued this stuff ad infinitum on hairloss sites, but keep coming up with contradictions.


My opinion is that being "outside" during the cool days, or the sunny ones, would probably tell nature that you "needed" you hair to protect you when you were young-------------------but even if I were right, it would take evolution how many thousands of years to begin to act on that if we had children attend school outdoors for several hours a day? Its practically a moot point. We do know this however, the girls sure as hell have nice hair, even now. ANDRO-genic alopecia anyone






Im trying topical beta sitosterol on the LEFT side of my chin for a few weeks (the untreated side of the peppermint oil experiments). I'll relate what I get. Rose hips, arnica, and clove are all the ideas I have left that appear to be anti-androgenic AND not angiogenesis inhibitors.

 

[tino]

Tino wrote:

Still a big mystery are the thoughts of the nature.Why the scalp skin?And basically why the frontal and vertex scalp,and not the occiptal parts?To my theory,that the system negelected to protect hair in the case of unfavourable genetic,during which the system has to protect vital parts in the first line,suits not the fact,that hair follicles beyond the frontal and occiptal scalp,were also not worth to keep in metabolic activity.Frontal and especially vertex scalp,is mostly exposed to sunlight.Sunlight can induce skin cancer-mostly in pheomalnin caucasian individuals(Skin cancer in individuals of African, Asian, Latin-American, and American-Indian descent: differences in incidence, clinical presentation, and survival compared to Caucasians).male pattern baldness is also mostly common in caucasians and rare common in eumelain asians or africans(Current understanding of androgenetic alopecia

Tino,

We have had discussions for years on this website about how exactly selection made men bald in some areas of the earth with more regularity than others. Here is a review for you to consider, and as you do, you will probably come to the conclusion that we did: namely that it doesn't matter much.


Fact: Caucasians bald more than Asians
Fact: Africans bald more than Asians
Fact: Eskimos bald less than anyone

See the logical rut this leads into? Eskimos rarely bald at all, and have been "up north" for at least 5,000 years that anthropologists have determined. ALOT of East Africans in Somalia and Ethiopia go bald. If the sun is good for hair, why do so few Eskimos and Mongolians bald vs. Middle Eastern men who bald pretty regularily (depsite the fact that other Middle Eastern men appear to have some of the thickest hair on the planet?


Lets move to apes. Japanese Snow monkeys rarely bald. Other kinds of primates based near the equator bald ALOT, some almost always. Their is a lemur that always has blue eyes despite dwelling in equatorial parts of the earth. It makes no sense, but there it is.



Balding might have presented a "maturity" in evolution, or perhaps in the distant past, our ancestors lived such short violent lives, the males didn't need hair for too many years because most died off anyway while killing food and dragging it home. Who knows? We have argued this stuff ad infinitum on hairloss sites, but keep coming up with contradictions.


My opinion is that being "outside" during the cool days, or the sunny ones, would probably tell nature that you "needed" you hair to protect you when you were young-------------------but even if I were right, it would take evolution how many thousands of years to begin to act on that if we had children attend school outdoors for several hours a day? Its practically a moot point. We do know this however, the girls sure as hell have nice hair, even now. ANDRO-genic alopecia anyone






Im trying topical beta sitosterol on the LEFT side of my chin for a few weeks (the untreated side of the peppermint oil experiments). I'll relate what I get. Rose hips, arnica, and clove are all the ideas I have left that appear to be anti-androgenic AND not angiogenesis inhibitors.

I really love this board,because people here have good arguments which move me to further research.


As first....do you have a proove for the "fact" that africans bald more than asians?To my knowledge,the lowest male pattern baldness incidence is for africans.


I assume that you know the modern multifactorial view on pathogenesis,genetic and trigger of male pattern baldness.That includes nutrition.

Inuits have a very selenium rich diet.The incidence of prostata cancer and also of skin cancer there is very low.Remember that my mean thougts about Balding and UV Exposure,was TGF-beta.Selenium is a well known tgf-beta inhibitor by the natur of his antioxidant capacity(for example ".Therapeutic effects and molecular mechanisms of anti-fibrosis herbs and selenium on rats with hepatic fibrosis.").Finland however is very selenium poor,and finnisch population has a relative high male pattern baldness incidence.Finnish people have also a higher incidence of cardiovasculaer diseases.inuits are rather brown coloured than white

http://cebp.aacrjournals.org/cgi/content/full/12/9/926

Cancers of skin, bone, connective tissues, brain, eye, thyroid and other specified and unspecified sites in Inuit.Miller AB, Gaudette LA.

J Cancer Res Clin Oncol. 1983;105(1):76-8.
Skin cancer in Greenland 1955-1974.

I did not said that the sun is good for hair.You missunderstood something.I just said that pheomelanin types,are more sensitive to sun exposure induced skin cancer,and that caucasians and northern folk,are in general phomelanin types.And the fact that some asians or africans go bald too-exeptions proove the rule.


But...i will take no claim on the truth of my theory,your theorys are also very interesting,and i myself take it into consideration.


Appeal....female male pattern baldness has never been prooven as being androgenetic.Mutations in the CAG Repeats,or in the 5-alpha-Reductase genes,are never found in normandrogenic females.Mutations in CAG Repeats of the AR,or in the 5-alpha-Reductase genes,are only found in PCO-S Women.


If a regimen does not work propper,i think it is not the right way to declare that over week prooven side effects.For me,the first way would be,questions like:can the substances reach my follicle without a follicle targeting galenic.Or is the ph or the storage temperature right,is this the right synergetic addition to my base treatment etc.

 

[Bryan]

Fact: Caucasians bald more than Asians
Fact: Africans bald more than Asians
Fact: Eskimos bald less than anyone

See the logical rut this leads into? Eskimos rarely bald at all, and have been "up north" for at least 5,000 years that anthropologists have determined. ALOT of East Africans in Somalia and Ethiopia go bald. If the sun is good for hair, why do so few Eskimos and Mongolians bald vs. Middle Eastern men who bald pretty regularily (depsite the fact that other Middle Eastern men appear to have some of the thickest hair on the planet?

Lets move to apes. Japanese Snow monkeys rarely bald. Other kinds of primates based near the equator bald ALOT, some almost always.

Seems to generally support the hypothesis that balding evolved as a means to help cool the developing brain.

 

[bcapop]

Fact: Caucasians bald more than Asians
Fact: Africans bald more than Asians
Fact: Eskimos bald less than anyone

See the logical rut this leads into? Eskimos rarely bald at all, and have been "up north" for at least 5,000 years that anthropologists have determined. ALOT of East Africans in Somalia and Ethiopia go bald. If the sun is good for hair, why do so few Eskimos and Mongolians bald vs. Middle Eastern men who bald pretty regularily (depsite the fact that other Middle Eastern men appear to have some of the thickest hair on the planet?

Lets move to apes. Japanese Snow monkeys rarely bald. Other kinds of primates based near the equator bald ALOT, some almost always.

Seems to generally support the hypothesis that balding evolved as a means to help cool the developing brain.

Sorry, but that's the stupidest thing I ever heard :whistle: .

 

[Bryan]

Sorry, but that's the stupidest thing I ever heard :whistle: .

(Yawn)

 

[Pondle]

I don't buy the brain cooling hypothesis either. According to Setty (Hair patterns of the scalp of white and Negro males. Am J Phys Anthropol 1970;33:49­55) white men are four times more likely to than black men develop premature balding. Yet European phenotypes evolved in a cooler climate!

 

[harold]

citation from the study

"We were unable to identify androgen-responsive elements in the TGF-1 promoter. TGF-1 promoter activation by androgen is bald frontal DPC specific and is not observed in non-bald frontal DPC, suggesting that some intrinsic factor(s) in bald frontal DPC are required (data not shown). Factor(s) that are genetically involved in Androgenetic Alopecia would be the true target of the pathomechanism of the disease. Our modified co-culture system will provide clues to further explore the role of androgens in the regulation of hair growth."

Do they mean factors before tgf-beta induces his destroying work?

They are referring to the factor or factors which cause a difference in the RESPONSE of a given hair follicle to androgens (specifically in this case, whether or not TGF-1 is released in response to androgens).

Posted this before but something must have gone FUBAR....
The fat that they could not find any androgen responsive elemants to the TGF-Beta promoter leaves wide open the possibility that there is another step/messenger between androgen binding and the increase in production of TGF-Beta. Such as the increased production of ROS as reported by that Chinese group.
hh

 

[harold]

Unless there was significant selective pressure for or against baldness then it is something that is unlikely to have much evolutionary function for bad or for good. Unless of course it hitches a ride with another gene that predisposes for something more advantageous - ie more androgenic -> greater sex drive (and more male pattern baldness) -> more offspring.
combined with the fact that it is primarily something that occurs after the mate selection and production of offspring takes place in 98% of the people of the world in human history prior to this century and its probably a bit of a non-factor really.
hh

 

[michael barry]

Tino wrote:

I assume that you know the modern multifactorial view on pathogenesis,genetic and trigger of male pattern baldness.That includes nutrition.

Tino,

I have 2 uncles in their fifties. Both are somewhat overweight, one more than the other. Both eat fast food, dont excercise much (unless you count fishing and mechanic-type work excercise), and pretty much lead the Western lifestyle with the Western diet. Both these very likeable "good ol' boys" (we love'em) have very full thick heads of hair in their fifties with teenage hairlines. One uncles hairline hasn't even moved anywhere on the temples, but he is greying a bit, the other is still red-headed even though outside his eyes, their is the faintest rounding of the hairline. We are talking VERY thick hair.


My father has a uncle (my father is Norwood 5 in his fifties) who is almost seventy wtih thick, still-mostly dark hair. It used to be jet black above the man's very blue eyes. In his youth, he could have been a movie star. This guy has lived a fast, successful, fun-loving, and money-making (big time) life. He still has a full head of hair.



Its genetics man.





MONKEYS AND APES EAT TERRIFIC DIETS, AS NATURAL AS POSSIBLE. NONE SHOULD BALD SHOULD THEY, BUT RU58841 stops it cold
Its saddening to see people like you beat yourselves up over male pattern baldness and constantly trying to blame diets or shampoos or cultural habits. Diet can accelerate male pattern baldness and exacerbate it, and diets full of phytoestrogens might also delay it a great deal in those genetically predisposed, but there still were some bald folks in pre-ww2 Japan. Some people just have the genes man. But we DO HAVE successful treatments for it now (finas + spironolactone should stop your baldness, etc.).

 

[harold]

Tino wrote:

I assume that you know the modern multifactorial view on pathogenesis,genetic and trigger of male pattern baldness.That includes nutrition.

Tino,

I have 2 uncles in their fifties. Both are somewhat overweight, one more than the other. Both eat fast food, dont excercise much (unless you count fishing and mechanic-type work excercise), and pretty much lead the Western lifestyle with the Western diet. Both these very likeable "good ol' boys" (we love'em) have very full thick heads of hair in their fifties with teenage hairlines. One uncles hairline hasn't even moved anywhere on the temples, but he is greying a bit, the other is still red-headed even though outside his eyes, their is the faintest rounding of the hairline. We are talking VERY thick hair.


My father has a uncle (my father is Norwood 5 in his fifties) who is almost seventy wtih thick, still-mostly dark hair. It used to be jet black above the man's very blue eyes. In his youth, he could have been a movie star. This guy has lived a fast, successful, fun-loving, and money-making (big time) life. He still has a full head of hair.



Its genetics man.





MONKEYS AND APES EAT TERRIFIC DIETS, AS NATURAL AS POSSIBLE. NONE SHOULD BALD SHOULD THEY, BUT RU58841 stops it cold
Its saddening to see people like you beat yourselves up over male pattern baldness and constantly trying to blame diets or shampoos or cultural habits. Diet can accelerate male pattern baldness and exacerbate it, and diets full of phytoestrogens might also delay it a great deal in those genetically predisposed, but there still were some bald folks in pre-ww2 Japan. Some people just have the genes man. But we DO HAVE successful treatments for it now (finas + spironolactone should stop your baldness, etc.).

This is equivalent to saying - "the idea that smoking gives you lung cancer is ridiculous - I have 2 uncles who smoked all their lives and have great lungs. Its genetics."
As Tino said the idea of something being multifactorial in cause and having an interplay of genetic and environmental factors makes sense. It doesnt imply that a bald guy wouldn't be bald if he was vegetarian or a guy with a full head of hair would be bald if he had drunk less tea. You seem to have the idea that everyone is out to say "androgens don't cause androgenetic alopecia". Nobody is.
hh

 

[harold]

TGF-Beta and ROS in other tissues.
Only so much we can extrapolate from this but it is interesting.
hh

Transforming Growth Factor-beta Activation in the Lung: Focus on Fibrosis and Reactive Oxygen Species.
Koli K, Myllärniemi M, Keski-Oja J, Kinnula VL.
"Reactive oxygen species (ROS) can activate TGF-beta either directly or indirectly via the activation of proteases. In addition, TGF-beta itself induces ROS production as part of its signal-transduction pathway."

Role of oxidative stress in pulmonary fibrosis.
"As well as activation, differentiation, proliferation and apoptosis of fibroblasts seem related to the oxidant/antioxidant balance, and the maintenance of a high intracellular level of reduced glutathione (GSH) is considered crucial in providing a reducing environment within the cell, able to protect against oxidative stress. In those conditions where oxidants, either inhaled or produced by inflammatory cell, increase, the ratio between GSH and oxidized glutathione (GSSH) may lower, influencing a variety of cellular redox-sensitive signaling processes such as the activation of nuclear factor-kB (NF-kB) and activator protein-1 (AP-1) that lead to a transcriptional up-regulation of a number of genes involved in inflammation and/or fibrogenesis, including cytokines [interleukin (IL)-1,, tumor necrosis factor (TNF-alpha), IL-6] chemokines (IL-8), adhesion molecules (VCAM-1, ICAM-1) and growth factors (GM-CSF). I"

Reactive oxygen species mediates the apoptosis induced by transforming growth factor beta(2) in human lens epithelial cells.
"TGF-beta(2)-induced apoptosis in HLECs was preceded by an induction of reactive oxygen species (ROS) and a decrease in glutathione in the intracellular content, indicating that this factor induces oxidative stress in HLECs.....Finally, the cell death induced by TGF-beta(2) in HLECs was partially blocked by radical scavengers, which decreased the percentage of apoptotic cells, whereas these agents did not modify the growth-inhibitory effect elicited by TGF-beta(2) in these cells."

Isoform-specific activation of latent transforming growth factor beta (LTGF-beta) by reactive oxygen species.
"The three mammalian transforming growth factor beta (TGF-beta) isoforms are each secreted in a latent complex in which TGF-beta homodimers are non-covalently associated with homodimers of their respective pro-peptide called the latency-associated peptide (LAP). Release of TGF-beta from its LAP, called activation, is required for binding of TGF-beta to cellular receptors, making extracellular activation a critical regulatory point for TGF-beta bioavailability. Our previous work demonstrated that latent TGF-beta1 (LTGF-beta1) is efficiently activated by ionizing radiation in vivo and by reactive oxygen species (ROS) generated by Fenton chemistry in vitro. In the current study, we determined the specific ROS and protein target that render LTGF-beta1 redox sensitive......Taken together, these results suggest that ROS-induced oxidation in LAP-beta1 triggers a conformational change that releases TGF-beta1. Using site-specific mutation, we identified a methionine residue at amino acid position 253 unique to LAP-beta1 as critical to ROS-mediated activation. We propose that LTGF-beta1 contains a redox switch centered at methionine 253, which allows LTGF-beta1 to act uniquely as an extracellular sensor of oxidative stress in tissues."

Prooxidant-antioxidant shift induced by androgen treatment of human prostate carcinoma cells.
"BACKGROUND: Prostate cancer is a disease associated with aging. Also commonly associated with increasing age is a shift in the prooxidant-antioxidant balance of many tissues toward a more oxidative state, i.e., increased oxidative stress. We hypothesize that androgen exposure, which has long been associated with the development of prostate cancer, may be a means by which the prooxidant-antioxidant balance of prostate cells is altered.....METHODS: The androgen-responsive LNCaP and the androgen-independent DU145 prostate carcinoma cell lines were exposed to 5 alpha-dihydrotestosterone (DHT) and to the synthetic androgen R1881.....RESULTS: DHT at less than 1 to 100 nM (a concentration range encompassing the physiologic levels of DHT considering all ages) and R1881 at 0.1-1 nM concentrations were effective in inducing in LNCaP cells comparable proliferative responses and changes in oxidative stress. In contrast, neither DHT nor R1881 had any effect on the oxidative stress in DU145 cells.....CONCLUSIONS: Physiologic levels of androgens are capable of increasing oxidative stress in androgen-responsive LNCaP prostate carcinoma cells. The evidence suggests that this result is due in part to increased mitochondrial activity. Androgens also alter intracellular glutathione levels and the activity of certain detoxification enzymes, such as gamma-glutamyl transpeptidase, that are important for maintenance of the cellular prooxidant-antioxidant balance."

Reactive Oxygen Species Act at both TGF-beta-Dependent and -Independent Steps during Induction of Apoptosis of Transformed Cells by Normal Cells
"We have recently shown that TGF-beta-treated normal fibroblasts can induce apoptosis of transformed cells. The overall process was inhibited by antioxidants and radical scavengers, pointing to a role of reactive oxygen species (ROS). To define the ROS-dependent steps precisely, our experimental system was dissected into three phases. During phase I, TGF-beta1 induced production and release of apoptosis-inducing signal molecules by normal cells. In phase II, these signal molecules were transferred between normal and transformed cells. During phase III, transformed cells went into apoptosis. The use of antibody directed against TGF-beta revealed that TGF-beta was required only during phase I. Application of radical scavengers and antioxidants at defined phases revealed that reactive oxygen species are involved specifically with biochemical processes induced by TGF-beta in normal cells and early in signal transfer between normal cells and transformed cells. These data therefore point to a functional role of reactive oxygen species both for the TGF-beta1-induced signal pathway in normal cells and for the induction of apoptosis in transformed cells."

Nitric oxide in the human hair follicle: constitutive and dihydrotestosterone-induced nitric oxide synthase expression and NO production in dermal papilla cells.
"The free radical nitric oxide, generated by different types of epidermal and dermal cells, has been identified as an important mediator in various physiological and pathophysiological processes of the skin, such as regulation of blood flow, melanogenesis, wound healing, and hyperproliferative skin diseases. However, little is known about the role of NO in the human hair follicle and in hair cycling processes. Here we demonstrate for the first time that dermal papilla cells derived from human hair follicles spontaneously produce NO by measuring nitrate and nitrite levels in culture supernatants. This biomolecule is apparently formed by the endothelial isoform of nitric oxide synthase, which was detected at the mRNA and protein levels. Remarkably, basal NO level was enhanced threefold by stimulating dermal papilla cells with 5alpha-dihydrotestosterone (DHT) but not with testosterone. Addition of N-[3-(aminomethyl)benzyl]acetamidine (1400W), a highly selective inhibitor of inducible nitric oxide synthase, restrained the elevation in NO level induced by DHT. Analyses of DHT-stimulated cells at the mRNA and protein levels confirmed the expression of inducible nitric oxide synthase. These findings suggest NO as a signaling molecule in human dermal papilla cells and implicate basal and androgen-mediated NO production to be involved in the regulation of hair follicle activity."

 

[Bryan]

Nitric oxide in the human hair follicle: constitutive and dihydrotestosterone-induced nitric oxide synthase expression and NO production in dermal papilla cells.
"The free radical nitric oxide, generated by different types of epidermal and dermal cells, has been identified as an important mediator in various physiological and pathophysiological processes of the skin, such as regulation of blood flow, melanogenesis, wound healing, and hyperproliferative skin diseases. However, little is known about the role of NO in the human hair follicle and in hair cycling processes. Here we demonstrate for the first time that dermal papilla cells derived from human hair follicles spontaneously produce NO by measuring nitrate and nitrite levels in culture supernatants. This biomolecule is apparently formed by the endothelial isoform of nitric oxide synthase, which was detected at the mRNA and protein levels. Remarkably, basal NO level was enhanced threefold by stimulating dermal papilla cells with 5alpha-dihydrotestosterone (DHT) but not with testosterone. Addition of N-[3-(aminomethyl)benzyl]acetamidine (1400W), a highly selective inhibitor of inducible nitric oxide synthase, restrained the elevation in NO level induced by DHT. Analyses of DHT-stimulated cells at the mRNA and protein levels confirmed the expression of inducible nitric oxide synthase. These findings suggest NO as a signaling molecule in human dermal papilla cells and implicate basal and androgen-mediated NO production to be involved in the regulation of hair follicle activity."

I've read that full study, not just the abstract. It's quite interesting, but I find a major fault in it, in that they tested only OCCIPITAL human scalp hair follicles, and not balding frontal follicles or androgen-dependent beard or other body hair follicles. That was quite a disservice to us, because it would have been fascinating to see how the nitric acid response differs from one type of hair follicle to another. Instead, they chose only one single "in between" follicle: the occipital kind. That's obviously a glaring oversight, and doesn't do us much good.

 

[tino]

TGF-Beta and ROS in other tissues.
Only so much we can extrapolate from this but it is interesting.
hh

Transforming Growth Factor-beta Activation in the Lung: Focus on Fibrosis and Reactive Oxygen Species.
Koli K, Myllärniemi M, Keski-Oja J, Kinnula VL.
"Reactive oxygen species (ROS) can activate TGF-beta either directly or indirectly via the activation of proteases. In addition, TGF-beta itself induces ROS production as part of its signal-transduction pathway."

Role of oxidative stress in pulmonary fibrosis.
"As well as activation, differentiation, proliferation and apoptosis of fibroblasts seem related to the oxidant/antioxidant balance, and the maintenance of a high intracellular level of reduced glutathione (GSH) is considered crucial in providing a reducing environment within the cell, able to protect against oxidative stress. In those conditions where oxidants, either inhaled or produced by inflammatory cell, increase, the ratio between GSH and oxidized glutathione (GSSH) may lower, influencing a variety of cellular redox-sensitive signaling processes such as the activation of nuclear factor-kB (NF-kB) and activator protein-1 (AP-1) that lead to a transcriptional up-regulation of a number of genes involved in inflammation and/or fibrogenesis, including cytokines [interleukin (IL)-1,, tumor necrosis factor (TNF-alpha), IL-6] chemokines (IL-8), adhesion molecules (VCAM-1, ICAM-1) and growth factors (GM-CSF). I"

Reactive oxygen species mediates the apoptosis induced by transforming growth factor beta(2) in human lens epithelial cells.
"TGF-beta(2)-induced apoptosis in HLECs was preceded by an induction of reactive oxygen species (ROS) and a decrease in glutathione in the intracellular content, indicating that this factor induces oxidative stress in HLECs.....Finally, the cell death induced by TGF-beta(2) in HLECs was partially blocked by radical scavengers, which decreased the percentage of apoptotic cells, whereas these agents did not modify the growth-inhibitory effect elicited by TGF-beta(2) in these cells."

Isoform-specific activation of latent transforming growth factor beta (LTGF-beta) by reactive oxygen species.
"The three mammalian transforming growth factor beta (TGF-beta) isoforms are each secreted in a latent complex in which TGF-beta homodimers are non-covalently associated with homodimers of their respective pro-peptide called the latency-associated peptide (LAP). Release of TGF-beta from its LAP, called activation, is required for binding of TGF-beta to cellular receptors, making extracellular activation a critical regulatory point for TGF-beta bioavailability. Our previous work demonstrated that latent TGF-beta1 (LTGF-beta1) is efficiently activated by ionizing radiation in vivo and by reactive oxygen species (ROS) generated by Fenton chemistry in vitro. In the current study, we determined the specific ROS and protein target that render LTGF-beta1 redox sensitive......Taken together, these results suggest that ROS-induced oxidation in LAP-beta1 triggers a conformational change that releases TGF-beta1. Using site-specific mutation, we identified a methionine residue at amino acid position 253 unique to LAP-beta1 as critical to ROS-mediated activation. We propose that LTGF-beta1 contains a redox switch centered at methionine 253, which allows LTGF-beta1 to act uniquely as an extracellular sensor of oxidative stress in tissues."

Prooxidant-antioxidant shift induced by androgen treatment of human prostate carcinoma cells.
"BACKGROUND: Prostate cancer is a disease associated with aging. Also commonly associated with increasing age is a shift in the prooxidant-antioxidant balance of many tissues toward a more oxidative state, i.e., increased oxidative stress. We hypothesize that androgen exposure, which has long been associated with the development of prostate cancer, may be a means by which the prooxidant-antioxidant balance of prostate cells is altered.....METHODS: The androgen-responsive LNCaP and the androgen-independent DU145 prostate carcinoma cell lines were exposed to 5 alpha-dihydrotestosterone (DHT) and to the synthetic androgen R1881.....RESULTS: DHT at less than 1 to 100 nM (a concentration range encompassing the physiologic levels of DHT considering all ages) and R1881 at 0.1-1 nM concentrations were effective in inducing in LNCaP cells comparable proliferative responses and changes in oxidative stress. In contrast, neither DHT nor R1881 had any effect on the oxidative stress in DU145 cells.....CONCLUSIONS: Physiologic levels of androgens are capable of increasing oxidative stress in androgen-responsive LNCaP prostate carcinoma cells. The evidence suggests that this result is due in part to increased mitochondrial activity. Androgens also alter intracellular glutathione levels and the activity of certain detoxification enzymes, such as gamma-glutamyl transpeptidase, that are important for maintenance of the cellular prooxidant-antioxidant balance."

Reactive Oxygen Species Act at both TGF-beta-Dependent and -Independent Steps during Induction of Apoptosis of Transformed Cells by Normal Cells
"We have recently shown that TGF-beta-treated normal fibroblasts can induce apoptosis of transformed cells. The overall process was inhibited by antioxidants and radical scavengers, pointing to a role of reactive oxygen species (ROS). To define the ROS-dependent steps precisely, our experimental system was dissected into three phases. During phase I, TGF-beta1 induced production and release of apoptosis-inducing signal molecules by normal cells. In phase II, these signal molecules were transferred between normal and transformed cells. During phase III, transformed cells went into apoptosis. The use of antibody directed against TGF-beta revealed that TGF-beta was required only during phase I. Application of radical scavengers and antioxidants at defined phases revealed that reactive oxygen species are involved specifically with biochemical processes induced by TGF-beta in normal cells and early in signal transfer between normal cells and transformed cells. These data therefore point to a functional role of reactive oxygen species both for the TGF-beta1-induced signal pathway in normal cells and for the induction of apoptosis in transformed cells."

Nitric oxide in the human hair follicle: constitutive and dihydrotestosterone-induced nitric oxide synthase expression and NO production in dermal papilla cells.
"The free radical nitric oxide, generated by different types of epidermal and dermal cells, has been identified as an important mediator in various physiological and pathophysiological processes of the skin, such as regulation of blood flow, melanogenesis, wound healing, and hyperproliferative skin diseases. However, little is known about the role of NO in the human hair follicle and in hair cycling processes. Here we demonstrate for the first time that dermal papilla cells derived from human hair follicles spontaneously produce NO by measuring nitrate and nitrite levels in culture supernatants. This biomolecule is apparently formed by the endothelial isoform of nitric oxide synthase, which was detected at the mRNA and protein levels. Remarkably, basal NO level was enhanced threefold by stimulating dermal papilla cells with 5alpha-dihydrotestosterone (DHT) but not with testosterone. Addition of N-[3-(aminomethyl)benzyl]acetamidine (1400W), a highly selective inhibitor of inducible nitric oxide synthase, restrained the elevation in NO level induced by DHT. Analyses of DHT-stimulated cells at the mRNA and protein levels confirmed the expression of inducible nitric oxide synthase. These findings suggest NO as a signaling molecule in human dermal papilla cells and implicate basal and androgen-mediated NO production to be involved in the regulation of hair follicle activity."

oh yes,that s really interesting stuff.Its almost the same in every cell type.There is some more about ROS and male pattern baldness,and also about ROS and AA.

I will search it.

 

[tino]

http://www.ncbi.nlm.nih.gov/sites/entre ... d_RVDocSum

Hmmm...Sebaceus glands secret and deliver Vitamin E.It seems that the non encymatic Antioxidants in the scalp,fights against the ROS overload there.

http://www.nature.com/jid/journal/v113/ ... 0554a.html

http://www.ncbi.nlm.nih.gov/sites/entre ... d_RVDocSum

Sure alopecia areata has a complete another pathogenesis.For example,TGF-beta can help the to stabilize the immune privileg there.But interesting too,it shows again that ROS and inflammation works together in the scalp skin

 

[tino]

Tino wrote:

I assume that you know the modern multifactorial view on pathogenesis,genetic and trigger of male pattern baldness.That includes nutrition.

Tino,

I have 2 uncles in their fifties. Both are somewhat overweight, one more than the other. Both eat fast food, dont excercise much (unless you count fishing and mechanic-type work excercise), and pretty much lead the Western lifestyle with the Western diet. Both these very likeable "good ol' boys" (we love'em) have very full thick heads of hair in their fifties with teenage hairlines. One uncles hairline hasn't even moved anywhere on the temples, but he is greying a bit, the other is still red-headed even though outside his eyes, their is the faintest rounding of the hairline. We are talking VERY thick hair.


My father has a uncle (my father is Norwood 5 in his fifties) who is almost seventy wtih thick, still-mostly dark hair. It used to be jet black above the man's very blue eyes. In his youth, he could have been a movie star. This guy has lived a fast, successful, fun-loving, and money-making (big time) life. He still has a full head of hair.



Its genetics man.





MONKEYS AND APES EAT TERRIFIC DIETS, AS NATURAL AS POSSIBLE. NONE SHOULD BALD SHOULD THEY, BUT RU58841 stops it cold
Its saddening to see people like you beat yourselves up over male pattern baldness and constantly trying to blame diets or shampoos or cultural habits. Diet can accelerate male pattern baldness and exacerbate it, and diets full of phytoestrogens might also delay it a great deal in those genetically predisposed, but there still were some bald folks in pre-ww2 Japan. Some people just have the genes man. But we DO HAVE successful treatments for it now (finas + spironolactone should stop your baldness, etc.).

You missunderstand me in fact.Harold said it all.



citation;Some people just have the genes man.

Yes,for example if we assume the polygene hypothesis,than for example four unfavourable genes will overwight Triggers like smoking or wrong nutrition.Only one,or two genes,may can only lead to breakout of male pattern baldness,if there is an extrinsic factor,like missing iron,or another kind of wrong nutrotion.Smoking etc.

 

[tino]

you wrote;Its saddening to see people like you beat yourselves up over male pattern baldness and constantly trying to blame diets or shampoos



you make me sick Its not allright to imply that i belive in a triggering effect of shampoos!I never said something like that.Its saddening that people like you,apparently dont understand the modern view on male pattern baldness as a multifactorial disease.