Unsaturation = Estrogenic, Saturation = Androgenic

Discussion in 'Scientific Studies' started by haidut, Oct 21, 2016.

  1. haidut

    haidut Member

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    Most people on the forum have read Peat's articles on PUFA and its great synergism with the estrogenic hormones. Peat has written that saturated fats have effects opposite to those of PUFA and there are studies showing feeding saturated fat increases androgen synthesis.
    I have been researching this topic for several months and have noticed that the same is true for steroids as well. The most unsaturated steroids are the 3 estrogens (estrone, estradiol and estriol), followed by aldosterone, the cortisol family, and even DHEA. In addition, the hormones with detrimental effects have no or only 1 free ketone group in their structure, and as such they are electron donors (i.e. metabolism inhibitors). So, the worst hormones as combination of these factors would be estradiol and estriol - i.e. highly unsaturated and without any ketone groups. The most beneficial hormones according to this classifications would be DHT, androsterone, allopregnanolone, and dihydroprogesterone. Unsurprisingly, Peat has written about the dangers of the estrogens and the benefits of the saturated steroids I mentioned.
    The study below discussed the estrogenic and androgenic effects of steroids in relation to their unsaturation/saturation and found that with the exception of androstanediol, all unsaturated steroids are estrogenic and similar to estrone. This includes androstenedione, testosterone, and some other testosterone derivatives. Androsterone, despite its structural similarity to estrone, was NOT estrogenic suggesting the saturatedness is behind its lack of estrogenic effects. While the study does not say it directly, I would venture a guess that the estrogenicity of androstanediol is probably due to its lack of ketone groups. Ray once said that to him testosterone was almost as dangerous as estrogen. I guess this study explains why.
    Perhaps most importantly, hydrogenation (saturation) of the hormone estrone changed its effects from estrogenic to androgenic. This immediately reminded me Ray's article that said tocopherol's primary biological purpose was to saturate PUFA. I am now wondering whether tocopherol is also capable of saturating steroids and whether this saturation ability is behind tocopherol's anti-estrogenic effects. If anybody is aware of a study that discusses this mechanism please share it.
    Anyways, I think this study demonstrates that the unsaturation of PUFA and its estrogenicity is not a coincidence and the same relationship extends to most steroids as well. It also suggests that the unsaturation/saturation of chemical compounds/chemicals we ingest or are exposed to can serve as a useful surrogate of their expected harm/benefit.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2122343/

    "...It is now recognized that substances of a more of less similar chemical nature to oestrone may have some degree of oestrogenic power even if their primary biological actiity if of quite a different nature. Further, it has been found possible to hydrogenate oestrone, which itself shows no male hormonal activity, to a substance having male hormone activity but no oestrogenic power."

    "...The first male hormone obtained, androsterone, isolated from male urine by Butenandt and his co-workers, was found to be non-oestrogenic by the vaginal cornification test and by a plumage test. Butenandt and Kudszus, however, have recently reported that trans-dehydroandrosterone, androstenedione, and testosterone cause opening of the vagina in the intact immature rat."

    "…Butenandt's work provided the first evidence that naturally occurring compounds might show the activities of both ovarian and male hormones. The three compounds found to be oestrogenic by Butenandt are all unsaturated, and therefore more similar to oestrone than is androsteroxe...We have also found that trans-dehydroandrosterone (1 mg. daily) will cause the appearance of female plumage in the Sebright bantam capon, an effect which can be produced by oestrone but not by androsterone."
     
  2. paymanz

    paymanz Member

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    Wow amazing.

    I remember he mentions unsaturated structure of PUFAs has some effect on water of the cell and makes it to take up water.

    Maybe one mechanism to swell the cell is that also in unsaturated steroids.
     
  3. OP
    haidut

    haidut Member

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    Oh yeah, anything unsaturated makes the cell more hydrophilic and less lipophilic. So, it starts to take up water. The primary effect of estrogen is to make the cell take up water, swell, and start dividing. PUFA has the same effect, so in that respect (i.e. cancerization of the cell) it is identical to estrogen. Saturated fats and steroids have the opposite effects.
     
  4. Wagner83

    Wagner83 Member

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    Very interesting.
     
  5. Ras

    Ras Member

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    Is it possible to hydrogenate hormones in vivo?
     
  6. mirc12354

    mirc12354 Member

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    So according to this 11-keto DHT is less saturated than regular DHT and more likely to cause damage?
     
  7. OP
    haidut

    haidut Member

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    That's what the million dollar question is. I suspect it is possible and maybe that is what tocopherol is doing. But it would probably be best to ask Peat.
     
  8. OP
    haidut

    haidut Member

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    No, where did you see that implied? On the contrary, 11-keto DHT is just as saturated as DHT but with an extra ketone group, so it should be even more pro-metabolic. That's one of the reasons to sell it actually - have a steroid with the androgenic effects of DHT but with stronger electron withdrawing properties. The steroid 7-keto-DHEA was started as a product with similar idea in mind.
     
  9. Ras

    Ras Member

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    He just replied to me, saying:

    "Unsaturation changes the way a lipid relates to water, making it less hydrophobic, but the resonance of double bonds has an important inductive effect on nearby groups; conjugated linoleic acid, for example has effects contrary to those of linoleic acid. I think the cytoplasm as a whole changes its properties (including hydrophobicity, pH and redox balance) cooperatively and coherently, with enzyme systems responding to those properties supporting more respiratory energy production, or alternatively a shift toward hypoxic metabolism, or varieties of catabolism. Progesterone’s ability to reverse the cell conditions of stress involves the activation of many enzymes that affect the oxidation state of lipids, but I think the main defensive reaction against an excess of C=C double bonds is to excrete them (with sulfation or glucuronidation), rather than reducing them."
     
  10. lampofred

    lampofred Member

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    @haidut Is progesterone unsaturated like testosterone or is it saturated?
     
  11. Lejeboca

    Lejeboca Member

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    Please excuse my jumping in. Just got curious and did a search: This site Progesterone
    shows that progesterone is unsaturated by having one C=C bond.
     
  12. Lejeboca

    Lejeboca Member

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    Does anyone know why Ray considers mead acid (omega-9), which is unsaturated and made by our bodies from sugars, is not harmful despite being a PUFA?
     
  13. lampofred

    lampofred Member

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    Not at all, thank you.

    That's interesting. So testosterone and progesterone are slightly unsaturated. And DHT/DHP, which are produced in response to estrogen, are fully saturated. I'm guessing that's to balance out the highly unsaturated nature of estrogen?

    I'm curious as to why we don't naturally produce fully saturated steroids in the fully oxidized, optimal condition. It's only when a bit of damage has been done and we are in a more reduced state that these fully saturated versions are produced.
     
  14. Lejeboca

    Lejeboca Member

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    Good question... Just a guess: By analogy with saturated vs unsaturated fatty acids, where the former are used more readily, in an optimal condition, the body maybe wants to use the "productive" steroids optimally (not too quickly/readily); hence they are made slightly unsaturated.
     
  15. lampofred

    lampofred Member

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    I think the answer to your previous question would probably answer my question as well... what is the purpose of the endogenous unsaturated fats and why are they not harmful like PUFA? The unsaturated bond of testosterone/progesterone being equivalent to the Mead acids.
     
  16. Lejeboca

    Lejeboca Member

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    Yeah, I am tempted to ask Ray about it :): . I will probably shoot an email question to the One Radio Network show with Dr. Peat tomorrow (I think Ray will be on 10am Texas time (CDT)) Can I use your question formulation? Or maybe you can ask him yourself?
     
  17. lampofred

    lampofred Member

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    Yup feel free! I always want to ask him questions on interviews but end up forgetting last minute, so it'd probably best if you did it lol.
     
  18. Lejeboca

    Lejeboca Member

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    I've sent this question just now. Hopefully the host can ask it for me. (I will not be able to listen live tomorrow..)
     
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