Recently, a reader and hair loss sufferer named “James K” sent me a very interesting e-mail pertaining to destroying androgen receptors. I have pasted most of his e-mail content towards the bottom of this post. Note that the androgen receptor is also known as NR3C4. Other options include looking into androgen receptor antagonists or androgen receptor silencing.
Destroying Androgen Receptors to Stop Hair Loss
Scientists know that male pattern hair loss (androgenetic alopecia) is caused by two factors that both need to be true:
- The presence of high levels of dihydrotestosterone (DHT — a derivative of testosterone) in the bloodstream and scalp. Note that 5-alpha reductase enzyme activity is what converts testosterone to dihydrotestosterone.
- The presence of a high level of androgen receptors on the scalp. Balding is a direct result of DHT binding to these receptors and then miniaturizing hair follicles. Many people can have high levels of DHT, but lack the androgen receptor (AR) gene. In those cases, they will not go bald. Finasteride drastically reduces DHT from binding to 5α-receptors, resulting in increased hair growth for many people.
Follicle sensitivity to the damaging effects of androgens varies by person. The number of androgen receptors on a scalp’s dermal papilla cells also varies from individual to individual. Research seems to suggest that genetic predisposition to AGA is polygenic in nature and there is no individual gene that is responsible for male or female pattern hair loss. Note that some sources seem to term “androgen receptors” as “DHT receptors”.
On a related note, eunuchs who are castrated never suffer from male pattern baldness. Their DHT levels are negligible for their whole lives. Also of interest is the androgen insensitivity syndrome intersex condition. I bet some blog readers wish they had such a problem.
Going back to “James K”, his main question pertained to why scientists have not done more research into destroying the androgen receptors on the scalp?
Or somehow destroying the androgen receptor gene? While we await CRISPR based gene modification, other techniques such as NdAgo have so far been a bust or overhyped.
How to Destroy Androgen Receptors?
I will quote “James K” in this section:
“I think that a cure would be to destroy these androgen receptors on the scalp, thereby making their sensitivity to androgens irrelevant. Androgen receptors are heat-liable and can be destroyed by trypsin.
Trypsin is possibly safe for topical application, but has the side effects of pain and burning. From a study on rats, trypsin causes hair cells to die and regrow slower, as it changed their gene expression.
Perhaps a safer/weaker version of this can be developed for hair loss? What do you think?”
My Thoughts
I am surprised that there is not much more research on this available online. Is it possible to destroy androgen receptors on the scalp without killing the actual hair follicles? Or is this nonsensical, with the only future solution being a genetic one? i.e., deactivating the AR gene responsible for hair loss?
Update: Someone sent me a link to research on silencing the androgen receptor.
The androgen receptor is continuously synthesized and “destroying” it is pointless because it will be re created again.
Maybe a life long treatment could attack the receptor, exactly like topical finasteride.
It is extremely important to point out that this hypothetical agent should never enter the bloodstream. The consequences would be catastrophical.
True that why it needs to be a topical everyday use.
Topical use doesn’t mean that it won’t enter the bloodstream. Your skin is an organ, capable of the uptake of many chemicals. For example: suppleting testosterone is also done by applying it to your skin, with the sole goal of reaching the bloodstream :)
CRISPR edition of the receptors will make them permanently invisible to DHT, instead of destroying them. Could be feasible by 2030, progress is very fast in gene editing.
Mediciness called S.a.r.d= selective androgen receptor degrader do exactly this
https://patents.google.com/patent/WO2016172358A1/en
I think it would be next to impossible to destroy these receptors without also damaging numerous other things in the scalp.
DNA or RNA editing/silencing, on the other hand could be much more targeted and I’ve got no doubt it could play a role in preventing AGA in the future, provided there are no effective, cheaper treatments by the time these technologies are in widespread therapeutic use. The bad news for us is that that could be a long while, in the 15-20 year timeframe.
Quark Pharmaceuticals already developed something that does this..it’s been quiet for a few years tho
Is it possible that we are still so far behind? what’s the latest news from Replicel and all the others? …
Shiseido must have results by now…
How is Guiliani doing with their WAY compound?
Admin,
any updates on exosomes?
Will have one by end of March most likely.
Something big?
No idea yet, but expect more feedback in February.
Who is the company for exosomes?
Gaining ethics approval for research that investigates destroying a naturally emerging component of the human body (which may not be well understood) would be highly difficult if not impossible. Unresolved questions remain about hair loss. Unresolved questions about androgen receptions probably remain too. Without all the answers, destroying receptors may lead to other adverse health consequences in humans. So, any research proposal on this topic may fail at the ethics gate before it even begins.
One mystery stands out to me with that one company POLARITYTE. They said they absolutely made skin with hairs on it and stated they had plans for cosmetic use with a multi billion dollar market they were years ahead of Tsuji.
Wyd were they thinking while theor stock went from 30 to 3? Huge mystery
There is no point in destroying the receptors.
Cells will produce new ones.
An interesting approach would be to block those receptors, but blocking may have other, adverse effects ’cause androgens are vital hormones, ya know.
Nonetheless, no one knows how male-patterned hair loss happens, why we bald on top but never on the sides.
When at med school, I did ask the professor f Derm who specializes in hair why the lack of knowledge and she said that no one cares…
Hehe
As someone else mentioned, AR gets continually re-synthesized. Moreover, the abundance of receptors is variable at a given time and can be affected by extenuating circumstances (such as the availability of DHT).
A recent study from South Korea
https://www.mdpi.com/2079-9284/6/4/66/htm
@Aleks thanks for this
Why cant someone bring out a shampoo now with that in?
I think they can, if one can find a compounding pharmacy that’s willing to do it…the paper didn’t disclose exact methods of preparations tho just the % of each extract in solution
I wonder if above two can also be added with this and compounded to leave in lotion
https://www.researchgate.net/publication/291389691_Identification_of_a_new_plant_extract_for_androgenic_alopecia_treatment_using_a_non-radioactive_human_hair_dermal_papilla_cell-based_assay
There is one Google it.
Destroying Androgen Receptors to Stop Hair Loss is nonsense … you soon can apply topical antiandrogen drugs and additionally topicals to set androgen receptors inop … both together will work great.
Anyway you will still need Lactate drugs for metabolism, Exosomes and electromagnetic Stimulation to get full head of hair. But even then you may still Need senolytics to kill senescent cells.
One needs to explain better what is meant by ‘destroying’, it’s too vague a word in this context because receptors on a cell are upregulated and downregulated all the time as far as I know so a cell may simply create new receptors.
If one means it as making a genetic/epigenetic change to the cell or somehow long term downregulation of the receptors then say that..
John doe, when will all these great options be available? We’ve been hearing similiar for the last 15 years.
Tomjones, you are right and thats so annoying! But just because this Hair Loss Industry is full of Snakeoils and frauds doesnt mean there is nothing in the Pipeline. … There are at least 30 Companies and another 30 Universities doing human clinical Trials and they just cannot all fail or all be liars.
John doe, many are liars in my opinion but not all. Many brag about their discovery to gain funding. They hype it up and some even give approximate dates of public availability. In my opinion they knew darn well that they would not have their product ready when they stated. Most drugs do not make it to market. With that being said, and of course the fact that mpb is a total beast, we will be lucky to get one legit side free treatment in the next 4 years.
Every drug and will treatment will have sides. Be happy if we get a treatment that works better than big 3
I’m just curious: what about suppleting testosterone (optionally in combination with 5-ar blockers)? An urologist told me: DHT and testosterone ‘level eachother out’, so if testosterone levels increase, DHT decreases and vice versa. This would implicate that suppleting testosterone should cause DHT levels to slowly drop. Anyone knows if this reasoning makes any sense?
PS. I mean: as I understand it, DHT is a more potent variant of testosterone, with a binding affinity to AR receptors 3/4 times higher than testosterone. So I was thinking: why would natural selection do this? The answer seems clear: if something happens to your testosterone levels, there is always the DHT
We really really just need a breezula or GT20029 to be able to block androgens at the receptor level, and lessen the sides of what we have today.
Blocking androgens wont be much better then fin in mostly prevention or a rogaine. Its not the solution to regrowing vast amounts of hair, but keeping hair is a vital thing we need.