New Here! Doubt Regarding DHT And ER-beta Receptors

[Dante]

(sorry for the bad english, not my 1st language)
Hi,
New Member here . I have become a big fan of peat's work especially the PUFAs . I have seen great studies been posted by @haidut for reversing chronic diseases like diabetes with simple measures like biotin, aspirin ,vitamin k2 etc. Before ray peat , i thought genetics and inheritance determine everything and you can't do much to change it (unless you go through gene therapy which to my knowledge is still in early stages) but that has changed.
I am trying to learn a bit of endocrinology though i don't have a medical background ( i know ray doesn't believe in 'lock and key receptors') but i am seeing that the protective and anti-inflammatory of DHT are due its metabolite 3-beta diol
which wikipedia says is an estrogen and has greater affinity for ER-beta receptors than estradiol !!
This study says that the protective effects of DHT are due to its action via ER-beta receptors by 3-beta diol.
The androgen derivative 5alpha-androstane-3beta,17beta-diol inhibits prostate cancer cell migration through activation of the estrogen receptor bet... - PubMed - NCBI
Since , estrogen is the enemy (it's excess), my question is that can two compounds ,say 3-beta diol and estradiol , act via same receptors(proteins) , ER-beta here and have different effects? Though DHT can't be aromatized but still can be turned into potent estrogens, so doesn't that make DHT dangerous also ?

Thanks

 

[ecstatichamster]

welcome, thanks for the study! Hope to see you here often.

 

[ecstatichamster]

I don't believe DHT can be turned into potent estrogens.

 

[charlie]

@Piyush Gaurav, welcome to the forum! Good to see you here.

 

[Dante]

I don't believe DHT can be turned into potent estrogens.

Hi @ecstatichamster ,
Thanks for the reply. If we assume any substance that binds to the so-called ER receptors , then 'medical science' calls that as an estrogen. Though can't be aromatized, I think that chart might not be complete. New metabolites keep getting discovered. I am simply stating what wikipedia said -" 3β-diol, is an endogenous steroid hormone. It is a 5α-reduced and 17β-hydroxylated metabolite of dehydroepiandrosterone(DHEA) as well as a 3β-hydroxylated metabolite of dihydrotestosterone (DHT). 3β-Diol is a selective, potent, high-affinity full agonist of the ERβ, and hence, an estrogen "

 

[DaveFoster]

Paging Dr. @haidut

Hi @ecstatichamster ,
Thanks for the reply. If we assume any substance that binds to the so-called ER receptors , then 'medical science' calls that as an estrogen. Though can't be aromatized, I think that chart might not be complete. New metabolites keep getting discovered. I am simply stating what wikipedia said -" 3β-diol, is an endogenous steroid hormone. It is a 5α-reduced and 17β-hydroxylated metabolite of dehydroepiandrosterone(DHEA) as well as a 3β-hydroxylated metabolite of dihydrotestosterone (DHT). 3β-Diol is a selective, potent, high-affinity full agonist of the ERβ, and hence, an estrogen "

Effects of 3-beta-diol, an androgen metabolite with intrinsic estrogen-like effects, in modulating the aquaporin-9 expression in the rat efferent ductules

"Fluid homeostasis is critical for normal function of the male reproductive tract and aquaporins (AQP) play an important role in maintenance of this water and ion balance. Several AQPs have been identified in the male, but their regulation is not fully comprehended. Hormonal regulation of AQPs appears to be dependent on the steroid in the reproductive tract region. AQP9 displays unique hormonal regulation in the efferent ductules and epididymis, as it is regulated by both estrogen and dihydrotestosterone (DHT) in the efferent ductules, but only by DHT in the initial segment epididymis. Recent data have shown that a metabolite of DHT, 5-alpha-androstane-3-beta-17-beta-diol (3-beta-diol), once considered inactive, is also present in high concentrations in the male and indeed has biological activity. 3-beta-diol does not bind to the androgen receptor, but rather to estrogen receptors ER-alpha and ER-beta, with higher affinity for ER-beta. The existence of this estrogenic DHT metabolite has raised the possibility that estradiol may not be the only estrogen to play a major role in the male reproductive system. Considering that both ER-alpha and ER-beta are highly expressed in efferent ductules, we hypothesized that the DHT regulation of AQP9 could be due to the 3-beta-diol metabolite."

It's affinity for ER-β receptors over ER-α may explain its effect, but I'm not an endocrinologist.

 

[Dante]

Though this is just a dissertation
http://dspace.library.colostate.edu..._items/csu01_storage/2012/03/01/file_1/123369

The title -> DIHYDROTESTOSTERONE ATTENUATES ENDOTOXIN, CYTOKINE, AND HYPOXIA-INDUCED VASCULAR INFLAMMATION

Quoting some of the contents
"DHT appears to be protective against cerebrovascular inflammation via conversion to 3β-diol and subsequent activation of ERβ in human brain VSM cells.
DHT metabolite/ERβ selective agonist 3β-diol also decreased cytokine-induced COX-2 expression in human brain VSM cells. Furthermore, DHT’s ability to reduce cytokine-induced COX-2 expression in human brain VSM cells was inhibited by the non-selective estrogen receptor antagonist ICI 182,780 and the selective ERβ antagonist PHTPP".

I suspect that messing with DHT may be dangerous because of its conversion to 3β -diol unless 3β -diol is a good estrogen ( i doubt there is any such thing as a good estrogen but new discoveries keep popping up).