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Contradictory issue....
Back to the roots: Causes and effects of elevated DHT
- Thread starter benjt
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I got three things to say:
1. I like the way this thread developed. This is exactly what I had in mind.
2. When my statements' are contradicting those of xRedStarx, assume the statements of xRedStarx to be correct. He definitely has more of a clue than I do.
3. On the matter of "When T is high DHT is also high" or vice versa (speaking in first order logic: "T high" <=> "DHT high") which was brought up one or two pages ago: That is definitely not correct and not always true. For example: If T serum base level is high and more free T is available (more T in the serum than your SHBG can handle), more T will be converted to DHT. Thus, the T increase leads to a DHT increase. As a counterexample, consider steady T levels but increased 5aR activity. This will lead to higher DHT, but lower T, because T is being converted to DHT and thus reduced. So you see, there is no material equivalence between the two. You cannot make any statement "if A then B" and vice versa; it always depends on what caused the alterations in T or DHT levels which determines the effect on the resp. other.
1. I like the way this thread developed. This is exactly what I had in mind.
2. When my statements' are contradicting those of xRedStarx, assume the statements of xRedStarx to be correct. He definitely has more of a clue than I do.
3. On the matter of "When T is high DHT is also high" or vice versa (speaking in first order logic: "T high" <=> "DHT high") which was brought up one or two pages ago: That is definitely not correct and not always true. For example: If T serum base level is high and more free T is available (more T in the serum than your SHBG can handle), more T will be converted to DHT. Thus, the T increase leads to a DHT increase. As a counterexample, consider steady T levels but increased 5aR activity. This will lead to higher DHT, but lower T, because T is being converted to DHT and thus reduced. So you see, there is no material equivalence between the two. You cannot make any statement "if A then B" and vice versa; it always depends on what caused the alterations in T or DHT levels which determines the effect on the resp. other.
According to this source DHT has the greatest affinity to SHBG; it binds more effectively to SHBG then any other hormone. But is there any scientific data whether DHT and T have greater affinity to AR then to the SHBG ? Of course bearing in mind most of T is bound, and only a small percentage is bio-available = free T, it seems T has grater affinity towards SHBG.
One of the main functions of SHBG is to balance / regulate level of free T and E and other steroids --> more SHBG less free T and E; less SHBG --> more free T and E ? And how does HPTA feedback mechanism control level of SHBG ?
It doesn't really matter the affinity of DHT, since all of it is bound to the ARs next to where it's locally produced, the excess leaks into the blood and gets either quickly metabolized, or bound to SHBG, but it serves almost no other function outside the local region.
Testosterone does not have high AR affinity in any case, except for muscle tissue, DHT is much more competitive, which is why your body produces DHT in the first place. I'd say the affinities don't really matter because of the different concentrations of steroid levels, which makes it meaningless to compare.
Yes, pretty much.
The body is a dynamic system, if there is normal T levels in the blood, your body downregulates thyroid hormones to stop testosterone stimulation. Same thing happens when Estrogen gets too high. If there is a lot of bio-available T and E, then the body up-regulates SHBG levels to normalize them, and vice versa. They all work together to keep optimal levels of total and free steroid hormones.
"an area the size of a pinhead on the skin of the penis has more activity of 5 alpha reductase than the rest of the body skin combined"
http://finasteridesyndrome.blogspot.com/p/dht-role.html
Is this true? Could skin DHT have something to do with sensitization of the glans penis?
http://finasteridesyndrome.blogspot.com/p/dht-role.html
Is this true? Could skin DHT have something to do with sensitization of the glans penis?
Yes it probably does.
But you need to understand that there is also 5-AR type I on the skin. Not to mention circumcised penises do not exhibit much less sensation.
xredstarx,
Do you have valid explanation why finasteride, increases serum testosterone level (and therefore probably because of aromatization estradiol level) by 15%, if only 5% - 10% or even less of T is naturally converted to DHT ? [Source: http://www.merck.com/product/usa/pi_circulars/p/propecia/propecia_pi.pdf page 8.]
Is this because DHT is 3 to 6 times more powerful than T. I believe the body is trying to compensate by increasing T for the lack of DHT being created. Estrogen increases as T increases to maintain homeostasis, right ? If that is true why body bothers with DHT production if it can produce sufficient quantities of T when there is lack of DHT ?
Do you have valid explanation why finasteride, increases serum testosterone level (and therefore probably because of aromatization estradiol level) by 15%, if only 5% - 10% or even less of T is naturally converted to DHT ? [Source: http://www.merck.com/product/usa/pi_circulars/p/propecia/propecia_pi.pdf page 8.]
Is this because DHT is 3 to 6 times more powerful than T. I believe the body is trying to compensate by increasing T for the lack of DHT being created. Estrogen increases as T increases to maintain homeostasis, right ? If that is true why body bothers with DHT production if it can produce sufficient quantities of T when there is lack of DHT ?
My junk turned into a piece of rubber after taking a few propecia tablets, lost its shape. Then it came back about 6-8 months after i stopped.
Yes, I believe it's a compensation mechanism for the lack of DHT, as seen in prostate and scalp concentrations of both before and after treatment.
Because DHT is the more potent androgen, and it does not aromatize. DHT can induce gene protein activation that is not replicable though testosterone. Probably due to it's higher affinity towards the androgen receptor, but I'm not entirely sure if the both have the same androgenic effects on tissue, I assume they do.
No it didn't.
My tissue is working fine. Care to explain?
Hey, do you guys think that if we raise naturally our testosterone level, our DHT level and/or 5ar would drop ?
I don't mean TRT, I mean having a diet and lifestyle that fits our body (with a good macro-nutrients ratio and all the micro-nutrients we need).
I wouldn't be illogical that hormone would be dependant on nutrients intake. This also mean SUN EXPOSURE. There is some evidence ( correlations and logics ) that lack of sun exposure causes some diseases (even if vitamin D is not lacking).
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I don't know if it's true, but % of young bald people in UK (maybe scandinavian countries too ) is high as well as hearth disease, and they do not experience a lot sun exposure.
I don't mean TRT, I mean having a diet and lifestyle that fits our body (with a good macro-nutrients ratio and all the micro-nutrients we need).
I wouldn't be illogical that hormone would be dependant on nutrients intake. This also mean SUN EXPOSURE. There is some evidence ( correlations and logics ) that lack of sun exposure causes some diseases (even if vitamin D is not lacking).
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I don't know if it's true, but % of young bald people in UK (maybe scandinavian countries too ) is high as well as hearth disease, and they do not experience a lot sun exposure.
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OT
Good advice ·Take care of your mitochondria, and they will take care of you.· do you know lipofuscina and NAC Acetylcysteine
Good advice ·Take care of your mitochondria, and they will take care of you.· do you know lipofuscina and NAC Acetylcysteine
Hey a**h**, Don't go "No It didn't". People react to the drug very differently thanks buddy. Go and do some research yourself about how androgens react with your junk. I'm not saying don't take propecia, i experienced **** side effects so I stopped and that side effect was rubbery texture of the junk and ED.
This article actually gives interesting information that levels of androgens found in occipital hair were not different between subjects with premature male pattern baldness and those who don't have male pattern baldness. And subjects who suffer male pattern baldness had increased levels of androgens in balding areas (vertex).
And here is another interesting article: http://www.ncbi.nlm.nih.gov/pubmed/16536818 In brief: DHT/T ratio was decreased in the vertex scalp hair after the individual received finasteride 1mg,`but there was found no significant difference in the ratio of DHT/T in the occipital scalp hair.
Unfortunately, neither article explicitly states how much is the level of DHT in occipital hair lower than in vertex, frontal hair in same individual .
Never heard of lipofuscina, but I heard about the benefits of NAC to boost glutathione level (I even wanted to buy it, but vitacost won't ship NAC to Canada :/ )
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I would make sense that hight DHT in balding scalp is due to low O2 in the tighest part of the scalp. Low O2 = more 5ar ---> more DHT.
What confirm this more, is that it is now known that high level of DHT will lead to hair follicles damage of even non-balding men.
However, DHT is NOT directly killing hair follicles. The reason is that your follicles work normally when there is 70% less DHT ( from taking finasteride). This mean that the remaining DHT won't do harm, so DHT to not directly kill hair follicles.
When I was reading some biology litterature, I found an harmful mechanism that was growing exponentially relative to the level of local DHT. I am pretty sure it is the source of miniaturization.
Yes it is true that low oxygen levels cause the DHT/ Estradiol ratio to increase; actually to be more precise low oxygen environment promote T to be converted to DHT by 5ard, rather than to estradiol by aromataze enzyme. Level of 5-ard is invariant on oxygen level. (?)
And frontal part of scalp is more tight which causes reduced blood and therefore oxygen supply which in turn causes increased DHT activity both inside and outside follicle. This is why front is the first line of defence when it comes to male pattern baldness. Occipital hair is located on occipital muscle which provides better oxygen and nutrient supply to hair follicles than frontal part of scalp or mid-anterior scalp.
My hypothesis is that the level of aromataze enzyme inside hair follciles also plays the significant role. By that I mean, if someone has very low level of aromataze then it doesn't matter how much of 5-ard is inhibited since in the end T can itself attach to AR and transmit its chemical signals. If there is critical level of aromataze inside DP cells then there is a 'battle' between 5ard and aromataze for T. And we must remember that estradiol and estrogen are beneficial for scalp hair, they transmit messages to nucleus which obviously stimulate scalp hair, unlike T and DHT which suppress/inhibit scalp hair growth and cause miniaturisation.
So to point out we want more estrogen/ estradiol to be generated inside hair follicles and less DHT/T to be attached to AR sites.
Please describe or provide some link of the process you are referring to.
This is nothing new, I believe that balding parts of the scalp had ~70% more DHT than non balding scalps, so reducing DHT inside the hair follicle by around 40% should give similar DHT concentrations in all areas of the scalp, thereby crossing the threshold of the balding trigger with confidence. I believe finasteride does in fact lower DHT inside the follicle by at least that amount in therapeutic doses.
ncbi.nlm.nih.gov/pubmed/8077349 said:
True, it's the androgenic response to DHT that causes upregulation of hair inhibiting proteins, like PGD-2 for instance. DHT is released in inflammatory environments, and PGD2 is anti-inflammatory, but also a hair inhibitor. It was found in much higher concentration on balding follicles than non-balding ones, even in non-occipital regions. PGD-2 regulates hair cycles and is more expressed during catagen and telogen phases. But in male pattern baldness, it is constantly expressed leading to consistently miniaturizing hair. It is also believed that DHT in high enough amounts and a long binding period is a 'switch' for increased local PGD-2 expression, whereby when triggered, cannot be reversed. This is something testosterone has much less ability to influence.
Ok this is my theory (I may have some parts wrong, but I'm pretty sure that the general idea is good) :
We know that the dermal papilla will miniaturize via cell senescence. Cell senescence is part of the theory of aging, which means that miniaturization of the dermal papilla can be documented by an aging mechanism. Fortunately, aging is currently well researched by passionate people (some bright people don’t want to die anytime soon). When aging will be fixed, baldness will be fixed (probably).
There is 7 causes of aging. Cellular senescence is one of them. It means that cells stop to divide in response to DNA damage and this leads to programmed cell death. Even if the mechanism is unclear, there is evidences that ROS (mitochondrial oxidative stress) and mitochondria health play a major part in cell senescence.
In balding scalp, follicles miniaturize via cell senescence and elevated DHT (dosage dependant). But how? DHT modulate nitric oxide in the dermal papilla cells. While nitric oxide is initially a good thing for hair growth, too much of it have an opposite effect. Nitric oxide causes mitochondrial biogenesis which leads to more ATP production in the dermal papilla cells. There is evidence of links between mitochondrial biogenesis induced by NO and cell dysfunction (via ROS). This elevation of NO will create more oxidation via elevation of superoxide. Superoxide in combination with nitric oxide will leads to peroxynitrite, and peroxynitrite destroys mitochondria oxygen production.
"NO or its derivatives(reactive nitrogen species: RNS) have three types of actions on mitochondria: 1) reversible inhibition of mitochondrial respiration at cytochrome oxidase by NO, and irreversible inhibition at multiple sites by RNS; 2) stimulation of mitochondrial production of superoxide, hydrogen peroxide, and peroxynitrite by NO; and 3) induction of mitochondrial perme- ability transition (MPT) by RNS. Similarly there are three main roles of mitochondria in NO-induced cell death: a) NO inhibition of respiration can induce necrosis(or excitotoxicity in neurons) and inhibit apoptosis if glycolysis is insufficient to compensate, b) RNS- or oxidant-induced signal transduction or DNA damage may activate the mitochondrial pathway to apoptosis, and c) RNS-induced MPT may induce apoptosis or necrosis" ---> Source here <---
This oxidative mechanism is exponential: "Even modest increases in the simultaneous production of superoxide and NO will greatly stimulate the formation of peroxynitrite; a 10-fold increase in superoxide and NO production will increase peroxynitrite formation 100-fold" ---> Source here <----
This explains why DHT is not bad at lower level. Since the process of oxidation is exponential, oxidation in the dermal papilla will resists to a much much lower level of oxidative stress. However, even a small increase in nitricoxide via DHT will increase a lot the oxidative stress via superoxide compensation.
ROS will damage the mitochondria and cells. When mitochondria ATP production is altered via oxidative stress, it can lead to programmed cell death (dkk1) . It has also been shown that mitochondria can stimulate mast cells (PGD2).
Low O2 -> elevated DHT -> elevated NO -> elevated oxidative stress (ROS) -> alteration of ATP production + DNA damage -> cell senescence + programmed cell death -> follicle miniaturization
This would explain why SOD's works well against hair loss (copper peptides study): it prevents the oxidative stress caused by DHT. Minoxidil increases NO. This could be why minoxidil stop to works long term, because the body will adapt and produce more oxidation to compensate the increased NO.
Shouldn't blackberries be a cure for male pattern baldness then?