Bayer Prolactin Receptor Antibody For Male And Female Pattern Hair Loss

[ChemHead]

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.

That depends on what stage of pregnancy. Most women gain hair and their skin looks better for some time during pregnancy. Afterwards, they lose that hair.

 

[Dimitri001]

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.

Well, isn't the study with the monkeys evidence of that? They regrew and maintained by addressing prolactin alone.

 

[baldco]

It seems like PRL might play a bigger role in hair pattern than previously thought. It's not only for cycling the hair growth seasonally but actually might be responsible for Androgenetic Alopecia pattern itself.

 

[pegasus2]

Well, isn't the study with the monkeys evidence of that? They regrew and maintained by addressing prolactin alone.

We'll see how that works in humans. The data is limited on prolactin's effect on human follicles, but what little data there is on the pattern of prolactin sensitive follicles seems to support that idea as well. Maybe I should've said there's no conclusive evidence.

 

[ChemHead]

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

Correct. This is why serum hormone levels do not accurately portray what is going on in the hair follicle... or really in any organ. However, there is a distinction between hair follicles making their own hormones vs the primary sources like gonadal. Gonads synthesize hormones from ground zero using cholesterol. Hair follicles don't technically make their own hormones. They need a supply of hormones in order to make their own hormones. Hair follicles enzymatically metabolize their supply of hormones from more "inert" hormones like testosterone, androstenedione, DHEA, progesterone, deoxycorticosterone, 11-deoxycortisol, etc. DHT and estradiol are more specialized hormones. They're meant to be made within specific tissues based on enzymatic expression, which is why their serum concentrations are much lower than other progenitor steroids.

That doesn't mean that your body doesn't make a lot of them. You just can't tell because your cells make those steroids through their enzymatic machinery, they do their work in the cell, and then they're further metabolized usually before they find their way back into the blood for elimination. By the time they're in the blood, they've been metabolized into something else. If you want to find out how much DHT your body produces, find its metabolites and measure those.

This is also why people don't realize how big of a deal using enzyme antagonists is. It's also why they fail to understand that supplementing with exogenous DHT is not even close to the same thing as your own cells creating their own through enzymatic metabolism. Imagine DHT supplementation being analogous to transporting loaves of bread on an open flatbed truck through a community of poor looters before it reaches its destination. If you're lucky, there will still be bread left for the original destination it was intended. This is the same reason why exogenous estrogen does nothing for hair unless you're using enough to cause MTF transition. It's all biochemical reaction kinetics. It's concentration, osmolality, and probability unless the cell is manufacturing the hormones itself.

 

[Ollie]

That depends on what stage of pregnancy. Most women gain hair and their skin looks better for some time during pregnancy. Afterwards, they lose that hair.

Yes but the loss is surely disproportionate to any gain. Loss in post pregnancy when feeding can be 500 hairs daily.

 

[Armando Jose]

Correct. This is why serum hormone levels do not accurately portray what is going on in the hair follicle... or really in any organ. However, there is a distinction between hair follicles making their own hormones vs the primary sources like gonadal. Gonads synthesize hormones from ground zero using cholesterol. Hair follicles don't technically make their own hormones. They need a supply of hormones in order to make their own hormones. Hair follicles enzymatically metabolize their supply of hormones from more "inert" hormones like testosterone, androstenedione, DHEA, progesterone, deoxycorticosterone, 11-deoxycortisol, etc. DHT and estradiol are more specialized hormones. They're meant to be made within specific tissues based on enzymatic expression, which is why their serum concentrations are much lower than other progenitor steroids.

That doesn't mean that your body doesn't make a lot of them. You just can't tell because your cells make those steroids through their enzymatic machinery, they do their work in the cell, and then they're further metabolized usually before they find their way back into the blood for elimination. By the time they're in the blood, they've been metabolized into something else. If you want to find out how much DHT your body produces, find its metabolites and measure those.

This is also why people don't realize how big of a deal using enzyme antagonists is. It's also why they fail to understand that supplementing with exogenous DHT is not even close to the same thing as your own cells creating their own through enzymatic metabolism. Imagine DHT supplementation being analogous to transporting loaves of bread on an open flatbed truck through a community of poor looters before it reaches its destination. If you're lucky, there will still be bread left for the original destination it was intended. This is the same reason why exogenous estrogen does nothing for hair unless you're using enough to cause MTF transition. It's all biochemical reaction kinetics. It's concentration, osmolality, and probability unless the cell is manufacturing the hormones itself.

Thank you ChemHead for the post
Pilosebaceous gland is capable synthethizing all these products parting cholesteroll.

Steroidogenesis in the skin: implications for local immune functions

The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it ...

www.ncbi.nlm.nih.gov

"Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol"

 

[ChemHead]

Yes but the loss is surely disproportionate to any gain. Loss in post pregnancy when feeding can be 500 hairs daily.

Agree. I think pregnancy puts a certain type of stress on the body (other than the obvious) by temporarily raising hormones to supraphysiological levels. After the pregnancy is finished, the body reacts in a reflexive kind of way... meaning enzyme and receptor expression was adjusted to accommodate two living beings and then when one of them literally just drops out, it probably causes a reaction similar to the one guys experience when they come off anabolic steroid cycles for bodybuilding. They're bodies suddenly become steroid deprived due to HPTA dysregulation and they become depressed, lose hair... just generally have a rough time for awhile until they're recovered.

 

[ChemHead]

Thank you ChemHead for the post
Pilosebaceous gland is capable synthethizing all these products parting cholesteroll.

Steroidogenesis in the skin: implications for local immune functions

The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it ...

www.ncbi.nlm.nih.gov

"Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol"

Very interesting. Thanks for the link. I wasn't aware of how prevalent steroidogenesis was in quite a few other tissues outside of gonadal and adrenal tissues. It looks like the vast majority of steroid synthesis in the skin comes from enzymatic metabolism, but it's fascinating how many other non-gonadal/adrenal tissues contain CYP11A1 and have the machinery to synthesize from cholesterol.

 

[whatevr]

"Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol"

So we can assume that the hair follicle's 17a-HSD enzyme being broken is the reason why it doesn't synthesize enough epitestosterone internally, since there are normal amounts in serum.

Characterization of 17alpha-hydroxysteroid dehydrogenase activity (17alpha-HSD) and its involvement in the biosynthesis of epitestosterone - PubMed

The present study permits to clarify the biosynthesis pathway of epiT. It also offers the opportunity to study gene regulation and function of this enzyme. Further study in human will allow a better comprehension about the use of epiT in drug abuse testing; it will also help to clarify the...

pubmed.ncbi.nlm.nih.gov

 

[Dimitri001]

So we can assume that the hair follicle's 17a-HSD enzyme being broken is the reason why it doesn't synthesize enough epitestosterone internally, since there are normal amounts in serum.

Characterization of 17alpha-hydroxysteroid dehydrogenase activity (17alpha-HSD) and its involvement in the biosynthesis of epitestosterone - PubMed

The present study permits to clarify the biosynthesis pathway of epiT. It also offers the opportunity to study gene regulation and function of this enzyme. Further study in human will allow a better comprehension about the use of epiT in drug abuse testing; it will also help to clarify the...

pubmed.ncbi.nlm.nih.gov

If I'm following your reasoning, based on connecting what Armando quoted about skin cells being able to produce hormones and epitestosterone being deficient in HFs, you're concluding that there's something wrong with the HFs enzyme for epitestosterone synthesis, is that right? (This may read as a condescending rhetorical question, but it's not, I'm asking genuinely.)

Or is there some additional piece of info that leads you to that conclusion?

Because if it's just that, I think you're making quite a leap there.

But I think the epitestosterone angle is interesting. I wonder if there's been any research into that.

 

[whatevr]

If I'm following your reasoning, based on connecting what Armando quoted about skin cells being able to produce hormones and epitestosterone being deficient in HFs, you're concluding that there's something wrong with the HFs enzyme for epitestosterone synthesis, is that right? (This may read as a condescending rhetorical question, but it's not, I'm asking genuinely.)

Pretty much. I don't think it's a leap at all - try to fit it into what we know thus far.

The conventional explanation is that baldness is a result of some mythical 'genetic sensitivity' to androgens.

But we know that one of the strongest natural antiandrogens is lacking in balding follicles (both in the balding fathers AND their children), and we know that baldness is genetic. So the result of 2+2 is there is no mythical 'genetic sensitivity', but there may be 'genetic impairment of enzymes responsible for synthesis of epitestosterone'.

It is still a piece of the same puzzle, just clearer.

EDIT: Let me clarify that perhaps you are right that me concluding 17a-HSD is broken is a leap. That may or may not be the case, it is 'speculated' to be the main pathway of epitestosterone synthesis, but the lack of epi-T may be also a result of increased clearance of the hormone, increased conversion to something else, or simply a lot more T than epi-T which skews the ratio (we don't have absolute measurements of epi-T levels in follicles yet to my knowledge - the one study that did supposedly measure them has really strange results which don't show much of a difference in absolute levels yet the ratio shows great differences between balding and non-balding, may be a peculiarity of the measuring techniques.)

 

[czecha]

If I'm following your reasoning, based on connecting what Armando quoted about skin cells being able to produce hormones and epitestosterone being deficient in HFs, you're concluding that there's something wrong with the HFs enzyme for epitestosterone synthesis, is that right? (This may read as a condescending rhetorical question, but it's not, I'm asking genuinely.)

Or is there some additional piece of info that leads you to that conclusion?

Because if it's just that, I think you're making quite a leap there.

But I think the epitestosterone angle is interesting. I wonder if there's been any research into that.

does estrogen grow hair or epitestosterone?

"
Several observations indicate that the antiandrogenic epitestosterone, a naturally occurring steroid in the human body and the 17α-epimer of testosterone, may suppress the conversion of androgen testosterone to DHT by inhibiting 5α-reductase activity (Nuck & Lucky, 1987;Starka et al.1989;Starka, 1993)."


I find it much more convincing stating that epitest suppresses t to dht, which means more t to e conversion (aromatase in tissue). I don't know why the fact that more T to E through 5ar inhibition gets so little attention, when E is literally the only thing that regrows hair

 

[whatevr]

does estrogen grow hair or epitestosterone?

"
Several observations indicate that the antiandrogenic epitestosterone, a naturally occurring steroid in the human body and the 17α-epimer of testosterone, may suppress the conversion of androgen testosterone to DHT by inhibiting 5α-reductase activity (Nuck & Lucky, 1987;Starka et al.1989;Starka, 1993)."


I find it much more convincing stating that epitest suppresses t to dht, which means more t for e conversion (aromatase in tissue). I don't know why the fact that more T through 5ar inhibition resulting in higer E gets so little attention, when E is literally the only thing that regrows hair

The cool thing about that study is that they gave those hamsters a testosterone:epitestosterone ratio of 1:5 and 1:10. and it suppressed the enlargement of the hair follicles (just like facial/body hair develops poorly with not enough T & DHT). However in balding people's follicles this ratio is up to 40:1 and in non-balding it is around 10:1. It seems like there is a bell-shaped curve where just enough androgenic activity results in maximum diameter of the hair follicle, and going too far below or above that the hair follicle miniaturizes again. That makes sense, since most hormones operate on a U-shaped curve.

 

[czecha]

does estrogen grow hair or epitestosterone?

"
Several observations indicate that the antiandrogenic epitestosterone, a naturally occurring steroid in the human body and the 17α-epimer of testosterone, may suppress the conversion of androgen testosterone to DHT by inhibiting 5α-reductase activity (Nuck & Lucky, 1987;Starka et al.1989;Starka, 1993)."


I find it much more convincing stating that epitest suppresses t to dht, which means more t for e conversion (aromatase in tissue). I don't know why the fact that more T through 5ar inhibition resulting in higer E gets so little attention, when E is literally the only thing that regrows hair

To me it just seems that inhibiting 5ar is the best mechanism of intrafollicularily increasing estrogen. We have no other ways of doing that except mtf transition protocols, and second best blocking the other thing T can convert to (dht)

this 100% matches my experience with finasteride too, when regrowth came with immediate E sides such as puffy nipples for the first time in my life

The cool thing about that study is that they gave those hamsters a testosterone:epitestosterone ratio of 1:5 and 1:10. and it suppressed the enlargement of the hair follicles (just like facial/body hair develops poorly with not enough T & DHT). However in balding people's follicles this ratio is up to 40:1 and in non-balding it is around 10:1. It seems like there is a bell-shaped curve where just enough androgenic activity results in maximum diameter of the hair follicle, and going too far below or above that the hair follicle miniaturizes again. That makes sense, since most hormones operate on a U-shaped curve.

Are you saying under 10:1 people have less hair again? How would that relate to aromatase if it does

 

[whatevr]

Are you saying under 10:1 people have less hair again? How would that relate to aromatase if it does

Well the difference between 1:10 and 10:1 is essentially 100-fold which is gigantic in biological systems, and I don't think the former really ever happens in humans unless there is a genetic trait resulting in epitestosterone dominance in the hair follicle. Maybe Asians tend that way, since they typically have hair that is finer in diameter yet seem less prone to pattern baldness.

Generally speaking since epitestosterone is both a strong AR antagonist as well as 5-AR inhibitor it would not only offer whole spectrum protection against ALL androgens, but also like Finasteride it would leave more testosterone available to convert to estradiol (in fact it would be superior than Finasteride since it also prevents T from docking to an AR, leaving it free to be consumed by aromatase).

But my guess is that an epi-T dominant hair follicle would not look healthy because aside from some androgen stimulation being necessary, having so little T in the follicle would also lead to a deficit of E2.

Pre-pubertal children typically have higher levels of epi-T than T so think of the kind of fine, light hair that most children have between 8-12 years of age, then for a lot of them as they hit puberty and the Epi-T goes down their hair actually thickens substantially. If they are not prone to baldness and the ratio stays up to the 10:1 range all is fine... but for the unlucky ones for whom the T ends up dominating too much they will start to bald.

There are ideal levels to all hormones, being too far in either extreme is bad.

 

[Dimitri001]

So how much research, if any, has there been into this epiT theory of hairloss?

Does anyone know of anything that refutes it?

 

[czecha]

So how much research, if any, has there been into this epiT theory of hairloss?

Does anyone know of anything that refutes it?

use the search function, we should stick to bayer here if we can't relate any of this to prolactin

 

[RolfLeeBuckler]

Back to topic of the German Company Bayer which Developed the technology:

„
It was with the latter that it completed the functional validation of the monoantithing resistance to Bayer's targeted prolactin (PRL) receptors - a drug that effectively promotes the growth of the hair of elderly redmas, and after six months of treatment, the number of hairs in the hair loss area nearly doubled, even in areas that had previously been nearly completely bald, and the effect continued for more than four years after the drug was discontinued - which led Bayer to transfer its development interest in the drug



" hair loss is just one of its indications, and the new target PRLR of HMI-115 antibody selection has many potential developments, such as endometriosis, lymphosarin disease and other autoimmune diseases

Xiao Ruiping revealed that the above indications have completed the development of clinical Phase I



, in addition, it has also developed innovative pipelines in various fields such as diabetic foot (DFU), rheumatoid arthritis (RA), and has been validated by the NHP platform for First-in-Class drugs

On a schedule, HMI-115, which treats lymphatic fibroids, is first expected to be approved for sale in 2024“

Xiao Ruiping: Through the last kilometer of translational medicine.

Guide: Xiao Ruiping has been working in the field of translational medicine for many years, and she is also one of the pioneers of translational medicine. In June, Bayer, a multinational drugmaker, announced that it would launch a Bayer

topic.echemi.com

 

[pegasus2]

Back to topic of the German Company Bayer which Developed the technology:

„
It was with the latter that it completed the functional validation of the monoantithing resistance to Bayer's targeted prolactin (PRL) receptors - a drug that effectively promotes the growth of the hair of elderly redmas, and after six months of treatment, the number of hairs in the hair loss area nearly doubled, even in areas that had previously been nearly completely bald, and the effect continued for more than four years after the drug was discontinued - which led Bayer to transfer its development interest in the drug



" hair loss is just one of its indications, and the new target PRLR of HMI-115 antibody selection has many potential developments, such as endometriosis, lymphosarin disease and other autoimmune diseases

Xiao Ruiping revealed that the above indications have completed the development of clinical Phase I



, in addition, it has also developed innovative pipelines in various fields such as diabetic foot (DFU), rheumatoid arthritis (RA), and has been validated by the NHP platform for First-in-Class drugs

On a schedule, HMI-115, which treats lymphatic fibroids, is first expected to be approved for sale in 2024“

(Before corona)

Xiao Ruiping: Through the last kilometer of translational medicine.

Guide: Xiao Ruiping has been working in the field of translational medicine for many years, and she is also one of the pioneers of translational medicine. In June, Bayer, a multinational drugmaker, announced that it would launch a Bayer

topic.echemi.com

Good find. I was figuring absolute best case scenario is 2026. Figure they lost a year due to cornavirus, that would put them at aiming for 2025 now. It's frustrating that we could've had what might amount to a cure by 2024 if not for these lockdowns

Edit: From the article.

"when asked about the impact of the new crown[corona] outbreak, Xiao Ruiping admitted that its research process is still on schedule".

It sounds like they are still aiming for 2024. This is fantastic!