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Dihydrotestosterone (DHT) Activates Estrogen Receptor Alpha

Discussion in 'Scientific Studies' started by Elephanto, Jun 10, 2018.

  1. Elephanto

    Elephanto Member

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    Mechanisms of dihydrotestosterone action on resveratrol-induced anti-proliferation in breast cancer cells with different ERα status

    ER-Alpha is the receptor through which Estrogen does most of its damage and tumor growth promotion, whereas ER-Beta has anti-proliferative properties and is activated by some phytoestrogens that have been shown to inhibit cancer growth and which consumption has been linked to lower cancer risks in epidemiological studies. This could explain why DHT may cause hair loss; while DHT is famed to be a non-aromatizable androgen this study shows that it directly triggers the most damageful estrogen receptor.

    In the same study we see that DHT reduces p53, an apoptotic gene which is muted in most cancers. For instance, estrogen and iron also inhibit p53. p53 induces igfbp3 which is low in male baldness pattern sufferers.

    I've also posted a study some times ago which shows that DHT is triggered by stress, and while it has some protective functions against stress it doesn't make sense that low-stress males who have lower DHT than highly stressed males are missing on health benefits. Stress is estrogenic and pro-cancer by triggering cortisol, estrogen and DHT.
     
  2. General Orange

    General Orange Member

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    Im just gonna pretend I didnt read this. :seenoevil:
     
  3. nwo2012

    nwo2012 Member

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    Yet no study or anything has ever actually proved/proven the existence of 'receptors'.
     
  4. nwo2012

    nwo2012 Member

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    DHEA is also increased in response to stress, It would also be a point of view that DHEA and DHT are increased in the stressed organism as protective rather than to compounding factors.
     
  5. nwo2012

    nwo2012 Member

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    You only need to remember RP's most important word in response to such studies, "context".
     
  6. Joeyd

    Joeyd Member

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    So would supplementing DHT be very dangerous re cancer etc.?
     
  7. Nebula

    Nebula Member

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    My hypothesis is abnormally high DHT in the context of low progesterone and chronically high cortisol causes imbalances in some tissues. While a moderate level of DHT in the context of a good level of youth hormones and low cortisol has additional protective effects against stress, while masculinizing an organism's tissues and brain. There's clearly a huge difference in how an organism responds to chronic high stress on cells in general and very brief acute stresses mostly only on muscles that can quickly be recovered from.

    I do think this suggests that DHT supplementation or even very intense exercise may have negative effects if youth hormones aren't already or simultaneously raised and if the amount of DHT supplemented is abnormally high.
     
  8. benaoao

    benaoao Member

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    Supplementing DHT for health reasons makes no sense in the first place. People should focus on lowering the stress response thus lowering estrogens, plus it will also help the thyroid.

    Bringing SHBG up a notch and improving insulin resistance are worth all the magic pills and creams around
     
  9. benaoao

    benaoao Member

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  10. Curiousman

    Curiousman Member

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  11. haidut

    haidut Member

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    That study is in-vitro and quite obviously worded to be highly favorable to resveratrol. Statements like the ones below cannot really be taken seriously.
    "...Dihydrotestosterone (DHT) has been shown to promote breast cancer growth via different mechanisms. In addition to binding to ERα, the DHT membrane receptor exists on integrin αvβ3. Resveratrol induces p53-dependent apoptosis via plasma membrane integrin αvβ3. Resveratrol and DHT signals are both transduced by activated ERK1/2; however, DHT promotes cell proliferation in cancer cells, whereas resveratrol is pro-apoptotic."

    Really?? Bummer, I guess all the human studies with androgens, and approved drugs like Drostanolone for treating breast cancer and/or gyno (also caused by estrogen) are fake then. DHT has well-proven anti-estrogenic effects in humans so even if it has some agonist activity on ERa that agonism is apparently more than outweighed by other anti-estrogenic effects (i.e. aromataze inhbition, 17b-HSD1 inhbition, prolactin reduction, etc).
    The point is not about specificity but about systemic effects. I can find you studies that show resveratrol is a potent anti-estrogen in some tissue or cell, yet its systemic effects are highly estrogenic and it can cause breast cancer.
     
  12. benaoao

    benaoao Member

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    It’s good that some forum members here go against the “DHT is flawless” narrative. Plus all narratives love their in vitro studies don’t they?

    DHT is quite an imperfect “savior” against e2 excess - which is the root cause of all dysfunctions. And supplementing DHT to balance out estrogens is like supplementing fish oil to balance out omega 6s.
     
  13. haidut

    haidut Member

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    Nobody said DHT is flawless. But to claim that it is estrogenic in the face of multiple clinical trials showing robust regression of HER+ breast cancer, gyno, obesity or even BPH (approved treatment in France) is unfounded. Progesterone is the main endogenous estrogen antagonist in both men and women before puberty. After puberty, that role in men seems to be taken mostly by DHT. So, it is probably the second-best endogenous estrogen antagonist and possibly even a better one for adult males who do not want to get the feminine experience. I have said multiple times on the forum that BOTH progesterone and DHT are worth increasing, but I don't see why DHT would be a bad option to oppose estrogen excess. When combined with some pregnenolone/DHEA and/or progesterone, it is probably much safer than T.
     
  14. benaoao

    benaoao Member

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    Everything you say it’s scientifically right of course, but DHT treatments fell out of preference because not as effective as anti-estrogens. The latter specifically address the cause of the disease isn’t it? Progesterone / T+DHT could make sense in post menopausal women / hypogonadal men.

    In younger males, the use of low dosed aromatase inhibitors will take care of most problems related to e2 - a diet that lowers insulin and/or raises SHBG will solve even more IMO. I wish my old man tried 6.25mg of exemestane a week with his T/e2 ratio of 10...

    Whole fruit instead of juice, (fat free) yogurt instead of milk, real lean protein instead of shakes, low GI high fiber solid carbs. When all of this is taken care of I’d maybe consider supplementing. Honestly who truly observes those?
     
  15. haidut

    haidut Member

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    Agreed, low dose AI like exemestane is certainly a viable approach assuming the person does not have downregulated 5-AR from finasteride, heavy use of marijuana or opioids, obesity, etc. Then even with AI their DHT synthesis won't move much. DHT is a neusteroid too and vital for male well-being. Most of the positive mental/mood effects of T are due to conversion to DHT. So, there are a number of ways to address the low androgen issue and all I am saying is that a definition of positive result needs to incorporate improvement in DHT synthesis/levels as well.
    Androgen Deficiency As The Main Cause Of Chronic Disease In Males
    Testosterone rapidly reduces anxiety in male house mice (Mus musculus). - PubMed - NCBI
    Testosterone's analgesic, anxiolytic, and cognitive-enhancing effects may be due in part to actions of its 5alpha-reduced metabolites in the hippoc... - PubMed - NCBI
    Testosterone's anti-anxiety and analgesic effects may be due in part to actions of its 5alpha-reduced metabolites in the hippocampus. - PubMed - NCBI
     
  16. benaoao

    benaoao Member

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    Right on^

    I’ve also read an article on SSRI/SNRI and amphetamines making males non responsive to clomid - not that clomid is awesome long term but if the hpta response to it is null, then there’s no other choice than androgen (or prog) supplementation. I tend to forget that people go to such extremes leaving them severely hypogonadal- or won’t really address those behaviors
     
  17. cyclops

    cyclops Member

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    What is this about? Kind of goes against everything Peat.
     
  18. benaoao

    benaoao Member

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    None of that is against Peat
     
  19. cyclops

    cyclops Member

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    Peat likes juice, he drinks lots of orange juice. He likes milk more then yogurt, and doesn't think yogurt is that great. Never heard him say to eat low GI high fiber carbs...
     
  20. Wagner83

    Wagner83 Member

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    Do you disagree with Ray on big pharma's AI? I'm pretty sure he disliked them very much.
     
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