Bayer Prolactin Receptor Antibody For Male And Female Pattern Hair Loss

[Dimitri001]

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.

Sure, but we should keep track even of negative outcomes, because that's important info, too, so we know what might be an inadequate dose/frequency of application. To figure out what dose/frequency works we need to know what's been tried and refuted, so further money/group buys can go to testing the next higher increment, instead of repeating what's been tested.

 

[Otrebor]

can this theory be plausible in your opinion?

the dht is not implicitly negative for the hair on the top of the head, it certifies that the latter are not very different from the hair on the arms, legs or beard. some strictly genetic conditions + the fact of having to do with a potentially "dead" area of the body can cause the dht to over-stimulate the follicles so as to accelerate the growth and stasis phases of the hair up to completely compromising the structure of the follicle for which stem cells are never enough to implement a "regular" process, a state of perennial stress and "rest" of the cells is created (this is where prolactin-regulated apoptosis, other pathways such as wnt and other elements intervene epigenetics), given that many possible treatments explore the growth pathways of the tumor and the immune system it seems plausible to me that with an abrupt acceleration of stem cell production the body autonomously tries not to face serious risks - prolactin according to some studies I saw some time ago has links with the JAK-STAT path -

Maybe minoxidil simply helps to make excess dht flow away locally and momentarily, both through the blood - by increasing the diffusion surface and thus making us shaggy - and by some remote pathway of cellular passage that has to do with the concentration of dht. in the cells (in this I could also theorize a state of "madness" of the follicles that begin to produce even more dht making the process a vicious circle), finasteride slows down the conversion, but it does so in a systematic way with possible side effects. Eventually these genetic characteristics of predisposition have to do with the scarce aromatase and the scarce production by the same cells of "natural antiandrogens" which I think we have already talked about on this thread.
after all every possible treatment that is mentioned here (except cloning) has to do either with blocking the conversion of testosterone to dht or with the cell-metabolic domain, we should find more solid links between prolactin and these two domains.

my opinion, I have recently been on the forum and I have recently started "studying", do not be very strict pls

 

[pegasus2]

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.

 

[John Difool]

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

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.

I don't agree on E3, I have visual effects of it working. And I am not the only one. Check the results on the patent for more cases.

WAY200070 is missing a few elements like GPER signaling which may be involved in the action on hair growth. Please try to not peanut butter everything with your very limited knowledge of hair loss beyond the wikipedia pages you learned by heart but couldn't understand beyond the title.

You truly belong the reddit crowd.

 

[Otrebor]

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.

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.
How prolactin can act in the area of hair growth is our question, which can lead to a reflection on all the connected paths.
It's not the optimal method but let's first take an empirical look at prolactin and then deal with its possible closer implications with the pathways it determines.
Let's take the example of an individual who may or may not have baldness, two ways:
- the pituitary prolactin is connected to the cellular prolactin, therefore it plays a role of apoptosis agonist. In this sense, in cases of prolactinemia it is possible that the hair follicles adapt to such high levels of prolactin perhaps with a balance of concentration at the cellular level or through the autonomous inhibition of prolactin receptors, and when we go to disinhibit the pituitary prolactin through dopamine agonists, the follicles go into crisis. After all, there are frequent cases of people losing hair with cabergoline, it can be a process inherent in cellular concentration and osmotic passage through the membrane (this will come in handy when we talk about dht).

- or pituitary and cellular prolactin are not so connected, but in the cells of the follicles it promotes apoptosis in any case.
Apoptosis in itself is not a malignant process, the body needs apoptosis in order not to undergo tumors or negative cell proliferation, but in baldness it is possible that this is a negative element due to previous conditions, but let's go in order ...

having said that, let's move on to the possible pathways affected by prolactin that could connect it with what we somehow know to be related to the development of baldness:
in my view the most interesting are: apoptosis and immune system (JAK-STAT).
So how is apoptosis related to hair?

We know that apoptosis is the cell growth inhibition mechanism as I mentioned earlier.
At this point we bring up the dht in conditions of hypoxia and precise predispositions concerning that precise part of the body:
Hypoxia -> DHT promotes hair growth by abruptly speeding up (in cases of predisposition) hair cycles -> Too fast, the follicles cannot keep up -> stem cells reproduce abruptly to try to keep up -> the organism alarmed by this sudden proliferation puts in place pathways to inhibit cell proliferation (apoptosis, wnt inhibition, inflammation mediated probably by the immune system) -> the cells of the hair follicles naively behave as if this were not happening and how if they weren't in hypoxic conditions then to solve the situation they further increase the sensitivity to DHT creating a vicious circle -> the hair follicles ultimately fall back on themselves, unable to die completely or produce more hair.
Injury, for example, can act as a balancing agent that forces the body to repair itself by putting a brake on the action of wnt inhibition, apoptosis and the "despotic" action of the immune system.

It is clear that these pathways are probably only a part, just as it is clear that they function for mechanisms and components / proteins etc. more and more detailed, here I dealt with a synthetic vision.
I 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).

Probably the prolactin antibody works as apoptosis plays an important role in the baldness process, through backup mechanisms it can also affect the wnt path, the proliferation of mitochondria in stem cells and so on. I do not exclude that it may also have a role in the concentration of androgens in the cell, or perhaps favor an oxygen supply so that the whole process would no longer take place in hypoxia.

As for the problem of concentrations between membranes, I would be really curious to inject enough dht into the scalp and see the results after a while, it would not be so paradoxical to observe a sort of "doped condition" for which the contribution from external disinhibits internal production, of course there would have to be resolved the condition of hypoxia (which is probably the real trigger) but I would still be curious to observe the data at the cellular level.

 

[badnewsbearer]

For 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?

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 puberty

 

[Armando Jose]

After all, there are frequent cases of people losing hair with cabergoline

In this case is a diffuse hair loss or a patterned shape as common hair loss?

I 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).

A lot of things can cause hair loss , ... a lot of genes implicated but our problem is always the same, the patterned hair loss

I would be really curious to inject enough dht into the scalp and see the results after a while

Me too, in healthy scalp, not affected by alopecia

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

IMHO, at first androgens receptos in scalp is the same in all areas.

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 puberty

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

 

[badnewsbearer]

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

Different 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

 

[Otrebor]

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.
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

 

[badnewsbearer]

Different 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

you should look into this study and open up the pdf its a neat study


the main takeaway is that for men, AR expression in frontal scalp was almost twice as high(!) as in occiputal scalp. in addition expression of 5AR subtype 1&2 where increased significantly in frontal scalp. in addition in men with Androgenetic Alopecia they observed much higher aromatase activity in the donor safe zone than the frontal scalp, this is new to me, more tissue estradiol makes sense due to lesser local conversion to dht but how this increases the expression is new to me.

we know that just bringing down the 5AR by 70% via finasteride works, it basically normalizes the 5AR2 expression pattern to occiputal scalp. however you are not even dealing with the androgen receptor expression promlem or the 5AR1 which is significantly expressed in outer rooth sheath, less so in DP but it does not matter bc dht can just diffuse to the target cells.

then this fucks with WNT and other cell signaling pathways and groefh faactors loke BMP, tgfb1, if-6 etc. androgens are obviously the root and it is local expression of genes that is the problem and this kust be regulated by other genes or how woukd this pattern come about?

in theory is the androgen degrader from kintor could degrade 60-70% of the AR then this could be really good but you are still dealing with 2times the 5AR activity and far less aromatase, peobably far less tissue dependent estradiol whoch promotes hair growth

 

[badnewsbearer]

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

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

 

[Otrebor]

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

Could you kindly link me some studies that explain this process in more detail, I would like to deepen.

Could the different expression of the genes for the hair on the top of the head compared to those behind the head be connected to what I hypothesized or do you see it as unlikely? Could they therefore be mechanisms implemented by the cells of the follicle given the most drastic conditions?

 

[badnewsbearer]

biological 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

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. sadly

 

[John Difool]

BAY is cure.

 

[John Difool]

For those who doubt about what BAY will deliver in 2025, just go back 56 pages prior. Amazing stuff.

 

[John Difool]

@hmmmmmmmm you were not supposed to take the blue pill as a suppository.

 

[Otrebor]

It does not rain us on the fact that androgens are the main culprits, however we must observe the conditions in which they act. I do not think it is optimal to discard prolactin a priori, it still has links with the immune system and above all with cellular quiescence.
The thing that really seems strange to me at the outset is how it is possible that the hair follicles even after many years of baldness progression are still present, almost as if in standby, waiting for something to reactivate their paths, halfway between death and the resurrection, until obviously time runs its course. This view may seem "anthropomorphic" but I seriously think that nature does not preserve something that supposedly causes problems, does not stop the processes of heralded death, then baldness can really be something accidental on the same level as a tumor or an autoimmune disease.
Androgens in the upper part of the head are found in a very particular part of the tissue, in hypoxia.
We temporarily remove androgens from speech, in hypoxic conditions a transcription factor called HIF1α comes into play, an element that, in synthesis, allows cells to adapt to the absence of oxygen.

https://www.nature.com/articles/s41580-020-0227-y

Hypoxia-inducible factor - Wikipedia

en.wikipedia.org

“HIF1α expression in haematopoietic stem cells explains the quiescence nature of stem cells for being metabolically maintaining at a low rate so as to preserve the potency of stem cells for long periods in a life cycle of an organism.

The HIF signaling cascade mediates the effects of hypoxia, the state of low oxygen concentration, on the cell. Hypoxia often keeps cells from differentiating. However, hypoxia promotes the formation of blood vessels, and is important for the formation of a vascular system in embryos and tumors. The hypoxia in wounds also promotes the migration of keratinocytes and the restoration of the epithelium. It is therefore not surprising that HIF-1 modulation was identified as a promising treatment paradigm in wound healing”

At this point I ask myself: what if baldness was just a path of cellular “lethargy” induced in response to some conditions present on the top of the head? Given some conditions / pathways, HIF1α is prevented from doing its job, on the other hand HIF1α, necessarily present, although decreasing over time, ensures that a metabolic maintenance of the stem cells is preserved, at least as long as this is possible, after the follicles go on permanent standby until they die completely. Probably the reason why miniaturization can take a long time depends on this, even the fact that baldness does not immediately take place with puberty can be indicative.

Role of HIF1α Regulatory Factors in Stem Cells

Hypoxia-inducible factor 1 (HIF1) is a master transcription factor that induces the transcription of genes involved in the metabolism and behavior of stem cells. HIF1-mediated adaptation to hypoxia is required to maintain the pluripotency and survival ...

www.ncbi.nlm.nih.gov

https://pubmed.ncbi.nlm.nih.gov/33326985/

This explanation lacks the main protagonist of baldness: DHT. So what role does DHT play in relation to hypoxia and especially HIF1α?
From this research it seems that in conditions of hypoxia DHT inhibits the expression of HIF1α ..

https://pubmed.ncbi.nlm.nih.gov/21856910/

But the curious thing is that in the presence of few androgens (so we can assume that this happens in pre-adolescence) and in hypoxic conditions HIF-1α favors the expression of the androgen receptor, probably this is the moment in which the process begins.

https://www.sciencedirect.com/science/article/abs/pii/S0960076010003602

Here reference is made to general organisms, and this may coincide with the fact that all men (even those with a perfect hairline) have less hair on the top of the head, but based on some predispositions that only a few need to be investigated (however a majority) develop baldness before actual old age.
It is as if HIF1α decrees its own disappearance, which in cases of baldness occurs totally or in any case much faster than the others. This is where genetics come into play which is something I haven't addressed yet.
This may be the origin of the androgen paradox, which if we think about it is not so paradoxical if we take into account the different conditions in which the hair follicles are found. With adolescence, we usually develop hair in the areas most supplied with blood and oxygen: face, chest, etc. generally someone appears slightly balding, in conditions of predisposition in the scalp a sort of hypoxia could form without any advantage: neither vascularization occurs and given the increasing presence of androgens HIF1α (which would allow the natural metabolism of stem cells) is inhibited more and more.
Referring back to what pegasus2 said in the first answer to my comment, I re-launch my hypothesis by trying to expand: dht stimulates growth in hypoxic conditions, this is therefore valid in vitro at a general level; but in vivo, and precisely in the scalp destined for baldness, this growth is likely to have gone mad: dht continuously stimulates hair growth but at the same time inhibits the expression of HIF1 which is necessary in hypoxic conditions for stem cells continue to perform their functions - the cells probably do not feel hypoxic due to the inhibition of HIF1α and therefore continue to produce DHT to maintain the hair growth function as if they were in another area of the body - it is like building a building without a foundation: the cells cannot keep up and cannot carry out their metabolism, the hair cycles become faster and faster until you get hair so fine that it is imperceptible, all this is a vicious circle because if HF1 on the one hand protects (as long as it can) the hair follicles and ensures a minimum sustenance - the minimum to generate ever finer hair - on the other hand, the expression of AR increases and since he is inhibited by the dht he decrees his slow suicide: a sort of civil war.

The Dht also inhibits the wnt path.

Before getting to prolactin, however, I would like to open a parenthesis that intrigued me a lot between hypoxia, glucose absorption and insulin resistance. In the condition of hypoxia the tissues tend to balance the lack of oxygen with more ways, as well as through the transcription factor that I have mentioned several times, the tissues tend to vascularize but above all to cause the cells to absorb more glucose.
Well in baldness we have established that the first phenomenon does not exist or that it is so scarce as to be irrelevant (I don't know if this has ever been investigated through methods that did not involve minoxidil) but what intrigued me is precisely the absorption of glucose :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144211/

Premature baldness has a fairly strong correlation with the metabolic syndrome of insulin resistance, which could be due to the cases of premature baldness that are increasingly present today. The Western diet is now characterized by the extreme use of sugars. Asians are getting there but until recently their diet was very varied and not excluding much more relevant genetic factors it is possible that the few cases of baldness are due precisely to a healthier diet (from this point of view) maintained in the over time.
This makes me increasingly think that hypoxia in the scalp of balding people is much more serious than the physiological one, there are mechanisms that prevent physiological adaptations


so we come to prolactin

https://www.sciencedirect.com/science/article/abs/pii/S0304394099009684

This study (unfortunately on rats) seemed interesting to me especially in the final.
This perhaps explains why it is important to inhibit prolactin before the aromatase in the scalp is definitively over, so when we still have some hair

The effect of prolactin and estrogen cross-talk on prolidase- dependent signaling in MCF-7 cells - PubMed

Estrogen and prolactin play important role in mammary carcinogenesis. The present study was undertaken to evaluate the effect of prolactin and estrogen cross-talk on HIF-1 α level and expression of some HIF-1 α- dependent signaling proteins. Since up-regulation of prolidase activity inhibits...

pubmed.ncbi.nlm.nih.gov

In the presence of Estradiol, prolactin inhibits HIF1α, therefore removing the prolactin increases HIF1α and the possibility that the cells maintain their metabolism. This may be related to the path of apoptosis that prolactin activates and at the same time may explain why in some cases it helps hair growth and in others it decreases it. Following my reasoning, there should be an element in the inhibition of prolactin that determines one of these four possibilities or perhaps combinations:
- The scalp comes out of the hypoxic condition in such a way that the dht acts as with all other body hair or at least reduces its negative effects
- Increase of aromatase up to genuine levels that ensure proper cell proliferation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672802/)
- For a series of mechanisms that I should investigate in the future, the inhibition of prolactin slows down / clears the process of cell madness in hair growth, creating a sort of respite (this could be linked to BMP4)
- End of the apoptosis process

Here I feel like self-criticism: I have not found studies on prolactin related to hypoxia, the only ones are these that concern women, and even if the factors, proteins and compounds are universal, it is possible that there are misunderstandings.
I also need to ascertain whether there is still a significant amount of estradiol in the bald scalp that could explain the second prolactin study.
For now I feel like HMI alone will probably not work because there will be other paths to correct first, my hope is of course that it works as well as it did with those monkeys.
Even the fact that it worked on monkeys should not be negatively accepted, it is true that monkeys could be like mice in this area, but it is still an empirical confirmation not just, all the possible links that prolactin remain to be found has with the process of baldness.

Hormone therapy is successful because it eliminates androgens from the equation in a certain sense, silences most of the negative effects, estrogens are directly connected with aromatase and in addition to favoring it, they protect it from the effects of androgens, all this in fact me seems connected, you just need to better understand the "backup" and interaction paths with some structural characteristics of the environment (only this in my view can explain the pattern of baldness and possibly the different level of severity of it)

HIF-1α stimulates aromatase expression driven by prostaglandin E2 in breast adipose stroma

The majority of postmenopausal breast cancers are estrogen-dependent. Tumor-derived factors, such as prostaglandin E[2 ] (PGE[2] ), stimulate CREB1 binding to cAMP response elements (CREs) on aromatase promoter II (PII), leading to the increased expression ...

www.ncbi.nlm.nih.gov

I think that if you stop the hormonal therapy, you go back to the starting state even if it is slowed down.
I have linked studies that do not necessarily have to do with baldness and the scalp, however they seem to me to be good starting points for understanding how the mechanisms work. There must be something in the environment determined at the start or by the follicle cells themselves at a certain point in their path, it is natural that the paths are influenced by the environment in which they occur, by factors such as: the presence of some metabolites, the concentration, the mechanisms of passage between membranes, etc. etc. Let me know what you think.

 

[John Difool]

TLDR. can you write a digest at the beginning of your posts and one paragraph conclusion?

 

[John Difool]

I am more inclined to think that she never considered hair loss as a market opportunity vs working for the greater goods as a women to treat breast cancer in other women. Not replying doesn't mean much beside that she didn't deny it as a scientific cancer research expert. We could speculate that she will try to investigate the hair loss path eventually (now she knows, thanks to you), although cancer seems a better mission that is keeping her and her team busy. Founding and grants may also be an issue in the hair loss research community. As for Bayer saying it doesn't work, it's also possible they meant it can work partially but wouldn't be replacement of HMI. I am still taking SMI oral at high dosage with the hope that it helps in dealing with high PR at the receptor level caused by higher E in my body (and why not for its main purpose too because of my blood serum level.) But I am not counting on it to be the cure. HMI on the other hand is much much more promising as a monotherapy while the jury is still out till we get results next year or so.

 

[Dimitri001]

You act like you're exposing some big secret, but I told people in the group buy thread that she said it doesn't work. Please at least be honest that I made people aware of everything that I knew, and made it clear that SMI might not work. Of course this researcher is trying to cure breast cancer not hair loss. She knows even less about hair loss than your local dermatologist, which isn't saying a whole lot, but I still wanted to point it out in the group buy. I also pointed out that the Bayer patent specifically states that competitive antagonists like SMI do not work. It's not like there was any harm in trying SMI. I do think it helped me some in the short time I was on it, but it is clearly not as efficacious as HMI-115, which was to be expected. View attachment 174378

By the way, the inventor of SMI stopped responding after she was shown Bayer's macaque study. If she thought it wouldn't translate to humans what was stopping her from replying with that?

Why did you decide to drop SMI?