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 present of high levels of dihydrotestosterone (DHT), a derivative of testosterone, in the bloodstream and scalp. 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?”
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.