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If there were a correlation between high prolactin level produced by the pituitary gland and hair loss then dopamine which restrains the production of prolactin would work for hair loss. However, it doesn't.
As I wrote before, people who are putting their money and risking their health on are part of a community. There is no point sharing progress with lurkers till there are real results. Hair cycle is 6 months and the results will come out as soon as we can demonstrate that it works.
Not just T suppression. if you talk about regrowth, you need to add E in some form, The estrogenic drug that cascades downstream and triggers signaling may do something that is missing in cismales.re: HRT - it's important to recognize that the evidence suggests that bulk of the regrowth is simply due to systemic T suppression
Understanding the above is how you can arrive very quickly at:
1. UT-34 is a great idea, operating in a way that could potentially give HRT results without sides if you're lucky
2. WAY-200070 is a bad idea, with no real chance of working because it's attempting to exploit comparatively marginal effects (estriol too)
so there's clear practical value in having these discussions on the quality of evidence in public, where beginners can see them
In my humble opinion we should talk about balancing pathways and hormones: our body has formidable self-balancing patterns and it is possible that baldness is only the result of one of these, or precisely the impossibility of an alternative for which the body folds in on itself, but we get there calmly.Minoxidil is a mild AR inhibitor, but its primary moa is believed to be through the promotion of growth promoting pathways not through the inhibition of androgen signalling. As for why androgens cause hair loss on the scalp and promote growth elsewhere, that's the million dollar question. DHT does stimulate hair growth under hypoxia, it is only under higher oxygen levels that it inhibits hair growth in vitro, so there may be something to your first paragraph.
its local expression of 5AR and androgen receptors in the frontal scalp. dhti in your mid scalp is more than twice as high as in your occiputal scalp. in addition there are much more androgen receptors as well. that combination increases the action of androgens by a lot. thereare probably much more genes involved and i am not sure how evolutionary such expression patterns come about, probably due to other generic programs that alter epiginetics, e. g. genefor andeogen receptor on the donor zone is methylated aka "silenced" and nobody onows why it is in thwt exact qrea when it is not in others. thereare genes whos resppnsibility it is to induce morphological structure like how do your fingers and limbs develop during embriogenesis, how do different brain structures develop. in case of the brain this is due to a gradient of a molecule which then raises expression of hox genes who act as local transcription factors that then run a genetic program to determine various structures. it could be similar with hair loss and homeomorphic transcription factora and explain the pattern that establishes itself during embyogenesis and comes to fruition once androgens raise during pubertyFor the time being, HRT and HMI-115 on monkeys have shown the best results.
It is possible that prolactin is no longer a big obstacle in those who undertake the HRT path because it somehow modifies the affinity of the receptors that remain susceptible to DHT alone.
In theory DHT shouldn't be bad for the body, there has to be a cascade of events that make it the enemy of that hair.
Maybe the body is stupid and believes that the lack of hair is Chad? Or is it, as I think, an imbalance of some kind?
In this case is a diffuse hair loss or a patterned shape as common hair loss?After all, there are frequent cases of people losing hair with cabergoline
A lot of things can cause hair loss , ... a lot of genes implicated but our problem is always the same, the patterned hair lossI cannot identify the causes of all this, I intend to study in more detail, but I do not think it is an incurable process, certainly we cannot act on the genetic causes but if the researchers identified a precise component to be regulated we could solve (and I say regular in a plausible way, without exaggerating or staying below what is necessary).
Me too, in healthy scalp, not affected by alopeciaI would be really curious to inject enough dht into the scalp and see the results after a while
IMHO, at first androgens receptos in scalp is the same in all areas.its local expression of 5AR and androgen receptors in the frontal scalp. dhti in your mid scalp is more than twice as high as in your occiputal scalp
Scalp hairs in fetus are orignated in the firsts months of life, acording to a centripetal growht wave, starting in the crownin case of the brain this is due to a gradient of a molecule which then raises expression of hox genes who act as local transcription factors that then run a genetic program to determine various structures. it could be similar with hair loss and homeomorphic transcription factora and explain the pattern that establishes itself during embyogenesis and comes to fruition once androgens raise during puberty
In this case is a diffuse hair loss or a patterned shape as common hair loss?
A lot of things can cause hair loss , ... a lot of genes implicated but our problem is always the same, the patterned hair loss
Me too, in healthy scalp, not affected by alopecia
IMHO, at first androgens receptos in scalp is the same in all areas.
Scalp hairs in fetus are orignated in the firsts months of life, acording to a centripetal growht wave, starting in the crown
BY the way, interestngs comments
in reality I was not aiming in that precise part of the comment to provide an answer to baldness, I was just looking for an interaction between inhibition of pituitary prolactin and regulation of the immune system / apoptosis which are pathways also implicated in baldness.In this case is a diffuse hair loss or a patterned shape as common hair loss?
A lot of things can cause hair loss , ... a lot of genes implicated but our problem is always the same, the patterned hair loss
Me too, in healthy scalp, not affected by alopecia
IMHO, at first androgens receptos in scalp is the same in all areas.
Scalp hairs in fetus are orignated in the firsts months of life, acording to a centripetal growht wave, starting in the crown
BY the way, interestngs comments
you should look into this study and open up the pdf its a neat studyDifferent Levels of 5α-Reductase Type I and II, Aromatase, and Androgen Receptor in Hair Follicles of Women and Men with Androgenetic Alopecia
In this study, 12 women and 12 men, ages 18-33 year, with androgenetic alopecia were selected for biopsies from frontal and occipital scalp sites. The…reader.elsevier.com
in reality I was not aiming in that precise part of the comment to provide an answer to baldness, I was just looking for an interaction between inhibition of pituitary prolactin and regulation of the immune system / apoptosis which are pathways also implicated in baldness.
I do not think that there is no hair loss comparable to the path / pattern of baldness but in any case it is indicative of the mechanisms of action of prolactin.
In reality I am trying to say that dealing with prolactin or dht (therefore systemic but also cellular elements) we enter a dark field that has not been investigated much with respect to its importance, above all the relationships between the "systemic" and the "particular" path are not investigated. and that is a problem.
Another problem is that if the predisposition to baldness has to do in some way with structural elements of our organism, neither tsuji nor stemson nor other alleged "drastic" solutions of this type will put an end to the problem (always assuming they arrive, which I doubt , but that's another story).
Everything that has to do with self-regeneration or the inhibition / stimulation of intrinsic pathways is in my opinion more important as well as closer in terms of development time, everything focuses on the etiology of baldness.
I don't want to be a spoilsport but apart from studies for their own sake few scientists have dealt with tracing a possible pathogenesis of baldness, those who directly propose solutions often do so starting exclusively from empirical cause-consequence observations: this makes hair grow -> is the solution to baldness, then it is obvious that thanks to a stroke of luck it is possible that the solution will come out. It does not mean that they do their job badly and that they know less than we do, I would be presumptuous to think so, but I still think that this way of acting is present.
I do not discredit anyone's work, on the contrary, I try more than anything else to make people understand how the forum can become a center for discussion on this rather than on the development times of a drug or a treatment, this is the competence of companies and we have little voice in chapter whether we like it or not.
HMI looks promising but I want to keep my feet on the ground as much as possible or at least look for the causes of its miraculous functioning.
Back to us,
I answer the other two statements:
1) Yes, they certainly have to do with particular genes, this does not mean that an approach is not possible (I want to dream that it is under our nose or in any case accessible in a short time), the fact that there is a pattern can be related to "problems structural "to which I referred above, some that come to mind can be:
- the poor circulation of oxygen in the scalp
- various predispositions to a sensitivity to DHT which probably intensifies with the course I described in the previous comment
- poor predisposition to aromatase or to the production of natural antiandrogens, perhaps the lack of oxygen is always involved in this, I will look for studies on this (for natural antiandrogens I am still looking for the comment of a boy who talked about them, I do not remember if on this thread or on others, it seemed very interesting to me)
- immune system that is too alert or easily irritable
2) My idea of injecting DHT into the scalp of a bald person is obviously impossible, first of all we don't know what quantity to inject, second: we would have significant side effects, third: it would probably go completely systemic without allowing us to observe the variations. Removed these difficulties could be a way to see how androgens work in the passage between the cell membrane and the system, in a nutshell to see how the hormones synthesized by the cell act: if remaining inside it and causing damage since the receptors are internal to the cell , or if going out and causing damage from the outside. (if anyone has any more in-depth study on the localization of receptors in relation to the action on the cell, pass it on to me, I intend to dedicate more time to investigate).
Cellular passage can occur autonomously by osmosis from the more concentrated solution to the less concentrated one or by active transport from the less concentrated solution to the more concentrated one: which category does dht (and prolactin) belong to? It is possible that there is some kind of madness process whereby cells produce excess dht since they do not perceive the normal and genuine state of equilibrium as if they were a bank printing money in an economic system that has now returned to bartering (forgive the metaphor ).
Why does sensitivity increase over time (moreover in an area where - according to studies - due to the lack of oxygen it should promote hair growth while exactly the opposite occurs)?
In my view, these are the most compelling issues to investigate and whether it is possible to resolve
Could you kindly link me some studies that explain this process in more detail, I would like to deepen.the andeogen receptor is a cytoplasmic receptors it resides in the cells cytoplasm where it is bound to so caled heat shock protein. upon binding of andeogens it dislocates from the proteins and travels to the nucleus where it binds to its promotors where it acts as a transcription factor. afterbinding there is a structural change of the locations on the dna strand of the downstream genes, they will somewhat coil up and RNA synthease will be able to reach them which will lead to transcriprion of those genes. these are the genes however that then mess with other pathways, in this case they mess with differentiation promoting and proliferation supporting pathways in the hair follicle like wnt.
a treatment by tsui would take DP cells from the occiputal scalp, those who tend to have less expression of AR and 5AR, proliferate them and implant them much like a hair transplant. so thsy are far less sensitive, however, i believe 5AR expression is not just highef in the DP cells but also the skin of the frontal scalp. so if you take the donor hair and implant it there is still significant signaling from surrounding tissue(both as in dht gets produced by the skin and can bind to DP receptors as they still have some of them just far less and second, if for example you still have other hairs around these produce those anti groeth factors which will eventually reach the hair follcile that is sensitive to androgens. it does not matter if your donor hair thaz you implanted is dht insensitive if the neighboring hairs f*** with the wnt pathway you get some of that too)
the way stemson can solve this is first of all completely get rid of the AR, just methylate it and the two 5AR genes as well. in theory this subtype of dp cells should not change upon renewal since epiginetics is "inheritation of expression patterns" so if the cells proliferate and some of them die, its successors should still have the same epiginetic profile, otherwise a hair transplant could never work.
in my opinion if you are jot on finasteride with hair transplant the problem is not just further recession of other sensitive area, it is that if you take cells from a save donor zone and plant them into a low estrogenic high androgemic emvironment they are still gonna get fucked up, its just gonna take a long time ans since kost men who get hair transplant are either old or on finasteride this will not be noticed.
this is just theory thoigh, the reality is that if semson mamages to create fully functional hair follicles that have heavily downregulated 5AR1&2 and AR genes then this will probably not be a problem and those hairs woll probablx stay around for a decade or two. hell by that time some anti 5AR microRNA therapy would be available that you can cream on your scalp(see OliX)
point is, we do not need to inject dht at all, we know whwre androgens act, we know what the result of their action is in this tissue this is studied very well. we do not understand how the pattern comes about and have a very vagua understansing of why some types of DP cells see andeogens as promoting (beard hair) whereas others have regression (scalp)
but in the end this is also down to these cells having different signatures(they express other genes differently) and this will have an effect on how androfens work as well. and role lf prolactin and estradiol have been barely understood at all. very complicated
i think it most definitely suggesta a much larger role of androgens than prolactin. and since androgen deprivation has no such effect as hmi did in the monkeys, i highly supspect that it is not going to work. like, i have been much mucb more hopeful about treatments other than this one that then failed but at least there were some known pathways thqt supported the theory, there is hyperlactemia and the fact that too much prolactin harms hair development but they are not indicative at all of such unheard of therapeutic effects. sadlybiological systems are all about thresholds, so the positive hair growth effects of systemic T reduction could simply be larger than any other negative effects HRT might have
so the mere existence of HRT results and how such regimens affect serum prolactin doesn't really help or hurt the chances of HMI working