Bayer Prolactin Receptor Antibody For Male And Female Pattern Hair Loss

[ChemHead]

thoughts on minitherapy approach?

This approach is better. This peptide will supposedly silence prolactinogenic activity even if prolactin binds PRLR along with the peptide and, because of that, it's easier to gain more useful information if you know you can reliably silence all prolactinogenic activity sytemically. With the other approach, if it doesn't work, it's difficult to tell why exactly it didn't work. At least if this doesn't work, you'll know that the PRLR doesn't play a significant role.

Other than the side effects to look out for due to the obvious inhibition of PRLR, the other factors that have to be considered are receptor-independent effects of prolactin. Based on the research, it seems like it's probably not very likely that prolactin has PRLR-independent effects that are responsible for hair loss, but it could still be possible that prolactin may have receptor-independent side effects. Just something to look out for. There's not a whole lot of clinical research out there on these hormones that are typically and criminally labeled "female" hormones. I wish that estrogens and progestagens and other hormones like this weren't casually thrown into a "female" category. It obfuscates real research. These hormones have a purpose in both males and females and this "labeling" has caused decades of ignoring their potential roles in various diseases and disorders (imo).

I'm very pleased to see research into other hormones rather than continuing to beat a dead horse with the androgen receptor and DHT. They're all likely interconnected in the pathogenesis of Androgenetic Alopecia, but the industry's obsession over only this one element has been a source of disappointment to me for awhile.

 

[Ollie]

I'm not sure why clinical research shows no changes in serum prolactin levels from dutasteride use. Finasteride caused hyperprolactinemia for me. As far as why a 5AR antagonist would increase prolactin levels: if DHT has a role in regulating PRLR expression, then lowering DHT synthesis will cause lowered overall prolactinogenic activity and will, thus, likely cause an upregulation in prolactin synthesis to compensate for the lowered PRLR expression.

If prolactinogenic activity turns out to play a significant role in Androgenetic Alopecia, this would also explain the loss of efficacy of 5AR antagonists over time. Eventually, the lowered PRLR expression (caused by lowered DHT synthesis) is negated by an increase in prolactin synthesis to normalize prolactinogenic activity (which would explain elevated PRL due to a 5AR antagonist). And all of this, of course, is because genetic expression of some enzyme or receptor is higher than it should be in the hair follicle, but normal in the rest of the body... and when you attempt to correct that with pharmaceuticals, you fix the problem in the hair follicle and cause other problems due to deficiency in the rest of the body.

finasteride and dutasteride will cause a dramatic spike in prolactin if it has affected your Estrogen enough - Estrogen being the primary precursor to Prolactin. My E goes up 50% on finasteride and as a result my Prolactin absolutely sky rockets. If i control my E with an AI it normalises.

EDIT: Which is actually super f*****g weird now i think about it as Estrogen is the one hormone that allows for the greatest amount of regrowth - perhaps as long as Prolactin doesn't increase disproportionately greater than the increase of E.

 

[pegasus2]

Regarding side effects, most of the side effects from PRLR antagonism are desirable.

 

[FollicleGuardian]

I agree with you that autocrine/paracrine PRL has much more effect on the hair follicle than endocrine prolactin, but I don't think endocrine prolactin is closed off from HF cells. Look at hyperprolactinemia where scalp hair gets decimated. Either pituitary PRL is having a direct effect on the cells, or intrafollicular PRL is upregulated by serum PRL through the immune system, or upregulated by the same promoter as pituitary PRL. PRL research is still in its infancy, but it appears to me that all three of these are true. This is the first study confirming an autocrine PRL loop in breast tissue; in it they suggest targeting "both endocrine and autocrine/paracrine levels" to fight breast cancer. I would think the same strategy would be necessary for alopecia. BAY and SMI both do this, dopamine agonists obviously do not. (dopamine receptors have been found in adipocytes now, but they are not a promoter of PRL in the HF).

A key question is, how low does PRLR signaling have to be to reverse hair loss? Dopamine agonists don't tell us anything except that reducing endocrine PRL is insufficient. PRLR expression in the HF is different in mice, but this study shows that PRLR null mice grow significantly longer and thicker hair, whereas PRLR impaired mice do not. Unfortunately I don't know the level of PRLR signaling impairment in the heterozygote mice, but this tells us that, in mice, there is no benefit to partial PRLR antagonism. In order to improve hair growth it has to be complete inhibition or at least below a threshold that is lower than what is present in the PRLR +/- mice. Another factor is that the PRLR is also bound by growth hormone. Does GH have the same biological action on the receptor as PRL does in the HF? Pure speculation here, but I wonder if GH reverses hair loss through binding to the PRLR and preventing PRL from binding to it.


View attachment 158803
This is a table from the mouse study linked above showing that only full inactivation of the PRLR enlarged hair shafts. Also from this you can see that silencing the PRLR enlarges male follicles more than female. This aligns with the hair counts from the macaque study that found males responded better than females to the PRLR antibody, and studies showing that catagen genes are downregulated by prolactin in human female frontotemporal hair, and blocking prolactin causes apoptosis in those hairs while adding prolactin elongates them. This is the opposite of what has been observed in human male scalp follicles. This might partially explain the different patterns in female and male pattern hair loss. PRLR antagonism will likely only work on the vertex in women while working everywhere in men.


Prolactin: an emerging force along the cutaneous–endocrine axis

View attachment 158804

In mice the PRLR is not expressed in the HM, while in humans it's expressed in the HM only during catagen. The HM sits on top of the DP and contains the cells that produce the hair shaft. Androgenetic Alopecia pathogenesis might involve aberrant PRLR signaling in the matrix reducing proliferation during anagen. Silencing the PRLR for long enough might return the hair follicle to its normal state where PRLR is only expressed in the matrix during catagen, and that could explain why the macaque regrowth lasted for years after discontinuing treatment. When DP cell numbers drop below a minimum threshold cell proliferation stops. So my question, does the DP cell number dropping below this threshold cause the matrix to express PRLR and enter catagen


View attachment 158805
This is a handy but not up-to-date chart showing known regulators of prolactin. There was a Japanese twin study which found there might be a link between smoking and severity of hair loss, but it was a weak link. The only known significant promoters here of ePRL are estrogen and TRH, but neither appears to be the major promoter of prolactin in the HF, and TRH downregulated PRLR immunoreactivity in the outer root sheath.


When looking at prolactin's biological effects it's important to remember that they are both site- and sex-specific. There are multiple PRL and PRLR variants with differing biological actions. For instance, PRL induces cell proliferation in breast cancer, but stops it in the HF.


I believe 3 more have been found since this review was published.


This study found a role for PRLR in the pathogenesis of alopecia areata, independent of serum prolactin. Two additional studies found similar results, but two others found significantly increased serum prolactin levels in patients with AA. They all found a role for prolactin signaling in AA. From this study, "a significant positive correlation was found between the prolactin receptor and the SALT[severity of alopecia] score".
View attachment 158806

There's good reason to believe that prolactin plays an important role in the pathogenesis of Androgenetic Alopecia as well. The gene for PRL is next to an Androgenetic Alopecia risk locus, indicating a potential causal relationship. The remarkable regrowth of hair in bald stump-tailed macaques confirms that this is an area requiring further attention. I believe that PRLR antagonists will become part of the big 3. To fight Androgenetic Alopecia in the future people will antagonize the androgen receptor, upregulate the canonical Wnt pathway, and antagonize the prolactin receptor.

This is A-1 info right here. Thanks for the thorough post. I completely agree that the circuit probably can’t be closed. And that it would make more sense that lowering systemic levels are probably not doing anything because we need a combination. There is a threshold. We need local antagonists.

Regarding human growth hormone. Is there any reason to believe it actually has a function at PRL receptors at all? Might also be good to block PRLR so that HGH bind more to it’s main receptor rather than PRLR. This is also speculation.

Lastly you are right about site and gender specific functions. This is interesting. From what I have seen the research actually points to PRL being good for womens hair.

 

[pegasus2]

Regarding human growth hormone. Is there any reason to believe it actually has a function at PRL receptors at all? Might also be good to block PRLR so that HGH bind more to it’s main receptor rather than PRLR. This is also speculation.

It does activate the PRLR, but that doesn't mean it has the same effect as prolactin on hair. It could be neutral or even positive. GH already has a lower affinity for the receptor than PRL does, and a higher affinity for its own receptor, but any extra GH binding to its receptor increases IGF-1 that much more.

A crosstalk between GH- and PRL response is possible at multiple levels. In the human, GH can activate both the prolactin receptor (PRLR) and the growth hormone receptor (GHR). We have demonstrated that activation of the PRLR, but not the GHR, is inducing mammary tumors in transgenic mice.

The role of prolactin and growth hormone in breast cancer - PubMed

This review will focus on the role for prolactin (PRL) and growth hormone (GH) in mammary tumor formation. Much attention has previously been focused on circulating levels of GH/PRL in relation to mammary tumor formation. We will review data demonstrating that these ligands also could be...

pubmed.ncbi.nlm.nih.gov

 

[pegasus2]

A word of caution for people thinking that the PRLR will eliminate the need for androgen antagonists to combat hair loss. The AR is still necessary for male pattern baldness to occur. This is a fact and it's not going to change. The cause of hair loss is not Prolactin, it's androgens. Occipital scalp hairs are sensitive to prolactin yet they don't succumb to male pattern baldness. Only hairs that are sensitive to androgens can miniaturize. Now it may be that only hairs that are sensitive to both androgens and prolactin are susceptible to male pattern baldness. That could change things, but there's no evidence of that.

 

[ChemHead]

The cause of hair loss is not Prolactin, it's androgens.

I do not agree with this statement at all. If androgens were the cause of hair loss, then total suppression of androgenic activity would regrow a full head of hair and this simply doesn't happen. Are androgens and the androgen receptor tangled up in hair loss pathology? Certainly. Most steroid pathways are interconnected in some way, however. So, obviously, if you cause a change in one of them, you're likely to observe a change in another. For example: you alter the androgen receptor pathway... What downstream effects does that have? What effects does it have on estrogen receptor expression? How about aromatase expression? There are a multitude of other physiological responses to altering the androgen receptor pathway and that's only one pathway.

Honestly, at this point, it's ridiculous to even make such blanket statements like androgens or prolactin or whatever is the cause of hair loss. We're not dealing with a light switch ffs... we're dealing with the human body. It's so complex that we still have no clue how tf it works. Like... we're not even close to fully understanding it.

The best we can do is continue tinkering within the body by using any substance that elicits a direct physiological response to hair growth and then trying to reverse engineer the relationship between all the unique switches we messed with. We have to see how each switch effects the physiology and then we have to see how each switch affects the other switches and then how those combined effects change the physiology. It's like reverse engineering an alien computer program from machine code, except you don't have a decompiler. It's a lot of f'kin around, switch flipping, measuring, recording responses and then trying to make sense of all the seemingly random data you've collected.

 

[pegasus2]

I do not agree with this statement at all. If androgens were the cause of hair loss, then total suppression of androgenic activity would regrow a full head of hair and this simply doesn't happen. Are androgens and the androgen receptor tangled up in hair loss pathology? Certainly. Most steroid pathways are interconnected in some way, however. So, obviously, if you cause a change in one of them, you're likely to observe a change in another. For example: you alter the androgen receptor pathway... What downstream effects does that have? What effects does it have on estrogen receptor expression? How about aromatase expression? There are a multitude of other physiological responses to altering the androgen receptor pathway and that's only one pathway.

Honestly, at this point, it's ridiculous to even make such blanket statements like androgens or prolactin or whatever is the cause of hair loss. We're not dealing with a light switch ffs... we're dealing with the human body. It's so complex that we still have no clue how tf it works. Like... we're not even close to fully understanding it.

The best we can do is continue tinkering within the body by using any substance that elicits a direct physiological response to hair growth and then trying to reverse engineer the relationship between all the unique switches we messed with. We have to see how each switch effects the physiology and then we have to see how each switch affects the other switches and then how those combined effects change the physiology. It's like reverse engineering an alien computer program from machine code, except you don't have a decompiler. It's a lot of f'kin around, switch flipping, measuring, recording responses and then trying to make sense of all the seemingly random data you've collected.

I'm not going to debate this and derail this thread. I will just say that EVERY hair loss researcher in the world disagrees with you. Total suppression of a fire doesn't rebuild your house after it burns it down, does that mean that the fire wasn't the cause of it burning down? You can call my claims ridiculous, that's fine because I'm in very good company on this particular claim with the likes of Takashi Tsuji, Ralf Paus, George Cotsarelis, Garza, etc. Literally no serious researcher agrees with you.

 

[Selb]

I do not agree with this statement at all. If androgens were the cause of hair loss, then total suppression of androgenic activity would regrow a full head of hair and this simply doesn't happen. Are androgens and the androgen receptor tangled up in hair loss pathology? Certainly. Most steroid pathways are interconnected in some way, however. So, obviously, if you cause a change in one of them, you're likely to observe a change in another. For example: you alter the androgen receptor pathway... What downstream effects does that have? What effects does it have on estrogen receptor expression? How about aromatase expression? There are a multitude of other physiological responses to altering the androgen receptor pathway and that's only one pathway.

Honestly, at this point, it's ridiculous to even make such blanket statements like androgens or prolactin or whatever is the cause of hair loss. We're not dealing with a light switch ffs... we're dealing with the human body. It's so complex that we still have no clue how tf it works. Like... we're not even close to fully understanding it.

The best we can do is continue tinkering within the body by using any substance that elicits a direct physiological response to hair growth and then trying to reverse engineer the relationship between all the unique switches we messed with. We have to see how each switch effects the physiology and then we have to see how each switch affects the other switches and then how those combined effects change the physiology. It's like reverse engineering an alien computer program from machine code, except you don't have a decompiler. It's a lot of f'kin around, switch flipping, measuring, recording responses and then trying to make sense of all the seemingly random data you've collected.

I think androgens are definitely a starting point, but the runaway processes following androgen induced hair loss (miniaturization) make it so that it’s not as simple as cutting off androgens to fix baldness. Prolactin receptor blocking might be one way to recover the key components to allow for hair growth and cycling, breaking and reversing the miniaturization process. Pegasus mentioned estrogen earlier and I’m currently trying to find more evidence for how estrogen regrows hair and how prolactin inhibition regrows hair. Maybe they work off the same pathway

 

[ChemHead]

I will just say that EVERY hair loss researcher in the world disagrees with you.

Right... and clearly they have this whole hair loss thing all figured out because none of us have hair loss. I certainly don't think that every hair loss researcher in the world disagrees with me. I think disagreeing with what I've stated would be narrow-minded and foolish and, to be clear, I didn't state that androgens and the androgen receptor weren't part of the puzzle. They're just not the cause. It doesn't even make logical sense. Think about this in the context of aging. As you age receptor sensitivity only gets worse... insulin sensitivity gets worse, steroid hormone sensitivity gets worse, enzymatic activity becomes less effective, your body synthesizes fewer hormones... not more. Hair loss is not caused by too much of something. It's caused by too little of something. If hair loss were due to hyperandrogenic activity, then this condition would improve as you age and be at its worst when you're young and your receptor sensitivity is high and your steroid production is high. The opposite is true, though. As we age and produce less steroids, as our bodies decline in receptor expression and enzymatic expression, hair loss gets worse.

Researchers have been wandering around the same "androgen circle" for DECADES and it's yielded very little. They triggered a few physiological changes by toying with androgen receptors and 5AR and instead of exploring exactly why drugs like finasteride work, they ignore all the valuable information that comes from their use.. all the side effects that are clues to what is actually happening. Trust me, if big pharma wanted to figure out what causes PFS, they could figure that sht out in less than a year. Most researchers are exactly what you would expect coming out of university... trained to think in a small box... indoctrinated with falsehoods that they think are true. And then on top of that, the direction of any real research is heavily dependent on finance and profitability rather than pursuit of knowledge so any truly gifted researchers are usually stifled.

Seeing anyone in this industry pursuing research outside of androgens and the androgen receptor is a breath of fresh air. Maybe others will take a hint and follow suit and we'll start seeing the pieces fall into place.

 

[fearofthereaper]

Right... and clearly they have this whole hair loss thing all figured out because none of us have hair loss. I certainly don't think that every hair loss researcher in the world disagrees with me. I think disagreeing with what I've stated would be narrow-minded and foolish and, to be clear, I didn't state that androgens and the androgen receptor weren't part of the puzzle. They're just not the cause. It doesn't even make logical sense. Think about this in the context of aging. As you age receptor sensitivity only gets worse... insulin sensitivity gets worse, steroid hormone sensitivity gets worse, enzymatic activity becomes less effective, your body synthesizes fewer hormones... not more. Hair loss is not caused by too much of something. It's caused by too little of something. If hair loss were due to hyperandrogenic activity, then this condition would improve as you age and be at its worst when you're young and your receptor sensitivity is high and your steroid production is high. The opposite is true, though. As we age and produce less steroids, as our bodies decline in receptor expression and enzymatic expression, hair loss gets worse.

Researchers have been wandering around the same "androgen circle" for DECADES and it's yielded very little. They triggered a few physiological changes by toying with androgen receptors and 5AR and instead of exploring exactly why drugs like finasteride work, they ignore all the valuable information that comes from their use.. all the side effects that are clues to what is actually happening. Trust me, if big pharma wanted to figure out what causes PFS, they could figure that sht out in less than a year. Most researchers are exactly what you would expect coming out of university... trained to think in a small box... indoctrinated with falsehoods that they think are true. And then on top of that, the direction of any real research is heavily dependent on finance and profitability rather than pursuit of knowledge so any truly gifted researchers are usually stifled.

Seeing anyone in this industry pursuing research outside of androgens and the androgen receptor is a breath of fresh air. Maybe others will take a hint and follow suit and we'll start seeing the pieces fall into place.

They *are* the cause and the biggest puzzle piece. Something else might keep the follicles miniaturized, sure, but it can't be said loud enough: No androgens no hair loss!

 

[ChemHead]

They *are* the cause and the biggest puzzle piece. Something else might keep the follicles miniaturized, sure, but it can't be said loud enough: No androgens no hair loss!

You're right. Case closed.

 

[Ganked By DHT]

Well it is true that if u have no androgens, you dont get androgenetic alopecia. There are lots of case studies of this.

 

[ChemHead]

Well it is true that if u have no androgens, you dont get androgenetic alopecia. There are lots of case studies of this.

Like I said, it's interrelated. That doesn't mean it's causal. Castration at a young age will stop the cascade of events that contribute to the conditions that cause hair loss. But, without normal steroid production, that hair will not be normal. It certainly won't grow like normal without supplemental exogenous hormone therapy. Castration after you're bald just makes you a castrated bald man. Shoot up some estrogens, though, and you'll be well on your way to a full head of hair with a female hair line.

Hair loss is a multivariate issue. My theory on hair loss explains why finasteride works, it explains how hair loss is essentially the same problem in both men and women, it explains the discrepancy in different male patterns as well as the between male and female patterns. I not saying I have it all figured out. I'm just saying it's insanity to continue walking around in circles with androgens and ignoring other the very obvious roles of other hormones.

 

[Ganked By DHT]

Yes it doesn't regrow substantially. But we need something that works without modulating hormones.

 

[whatevr]

I still think one of the gravest sins of the hair loss world was not doing follow-up research on the implication of why a very strong natural anti-androgen, epitestosterone, is severely lacking in balding follicles. It explains away this entire concept of 'androgen sensitivity' in the first place, and figuring out a way to restore the enzyme producing would be like synthesizing your very own CPA (or stronger) in the follicle again. Done early enough it would most likely completely stop hair loss, no question about it.

But for whatever reason, that route wasn't deemed too interesting by scientists, and so we still don't have a damn clue what exactly causes the hormonal imbalance present in androgenic alopecia, which seems to be the root problem.

 

[Armando Jose]

Hair makes all its own hormones

Skin steroidogenesis in health and disease - Reviews in Endocrine and Metabolic Disorders

The skin is an important extra-gonadal steroidogenic organ, capable of metabolizing various hormones from their precursors, as well as of synthesizing de novo a broad palette of sex steroids and glucocorticoids from cholesterol. In this manuscript, we review the major steroidogenic properties of...

link.springer.com

 

[czecha]

Hair makes all its own hormones

Skin steroidogenesis in health and disease - Reviews in Endocrine and Metabolic Disorders

The skin is an important extra-gonadal steroidogenic organ, capable of metabolizing various hormones from their precursors, as well as of synthesizing de novo a broad palette of sex steroids and glucocorticoids from cholesterol. In this manuscript, we review the major steroidogenic properties of...

link.springer.com

The problem with the biohack route is that we can observe our follicles from the outside, but we have no idea what happens in them if I am not mistaken. We can get an idea with bloodwork, observation etc. what happens in the rest of our body when we take meds, but the human hair follicle is a black box to biohackers and only opens up a bit to researchers with million dollar labs, who of course research under established paradigms.

We can already systemically modulate so many things in our bodies, yet the only things that grow a lot of hair aren't worth it for the average male still. There is another way, it just hasn't been discovered yet.

I suspect that if proper biohackers were running state of the art labs instead of having to rely on observation and other not very helpful tools to theorize what happens in human hair follicles, they could figure this sh*t out or at least have a better shot than tsuji et al who is now starting to sell hair lotions

so much hair loss research and all we got outside of forums as hair meds are medications that weren't intented for male pattern baldness in the first place and are thus coincidence discoveries that are like 40 years old. just lol @ male pattern baldness research honestly

I still think one of the gravest sins of the hair loss world was not doing follow-up research on the implication of why a very strong natural anti-androgen, epitestosterone, is severely lacking in balding follicles. It explains away this entire concept of 'androgen sensitivity' in the first place, and figuring out a way to restore the enzyme producing would be like synthesizing your very own CPA (or stronger) in the follicle again. Done early enough it would most likely completely stop hair loss, no question about it.

But for whatever reason, that route wasn't deemed too interesting by scientists, and so we still don't have a damn clue what exactly causes the hormonal imbalance present in androgenic alopecia, which seems to be the root problem.

how do we explore that angle? is there no compound we can try? we will clearly have to do it ourselves somehow, if we want that angle explored

 

[Ollie]

Just some food for thought but it’s interesting women lose increasing amount of hair when they’re pregnant and also post pregnancy when prolactin levels are the highest - with the loss returning to baseline once they stop feeding and prolactin returns to baseline.

 

[Armando Jose]

but the human hair follicle is a black box to biohackers and only opens up a bit to researchers with million dollar labs

It is not so dificult, not now with current technology. Only in order to trgger proper investigatios, we need know when start the pilosebaceous unit make its own signals/hormones? It would be a interesting research, I'll bet in the early infancy. and 100% operative at 4-5 years old.

they could figure this sh*t out or at least have a better shot than tsuji et al who is now starting to sell hair lotions

Sorry but imho hairs meds need be topical, we don`t must play with all our body.