DHT May Be Vital For The Morphogenesis Of Organism(s)

Discussion in 'Scientific Studies' started by haidut, Apr 16, 2020.

  1. haidut

    haidut Member

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    As many forum users know, the potent androgen DHT is one of the most vilified endogenous substances produced by the human body, second only to cholesterol. Aside from verbal vitriol published in mainstream scientific journals, this attitude of medicine towards DHT can also be estimated from the number of prescriptions for 5-alpha-reductase (5-AR) inhibitors such as the (in)famous finasteride/dutasteride (and less so androgen receptor antagonists such flutamine/bicalutamide) as those are the main pharmaceutical tools in the "war" against DHT. Those drugs are mostly prescribed to males and the number of prescriptions is in the top five prescribed drugs, behind only statins, PPI (anti-acid drigs), and blood pressure drugs. As a result of those prescriptions, there is a large and ever-growing number of males who experience long-term psychological and physiological decline despite the vehement denials by mainstream medicine and Big Pharma that those drugs are risky or cause any long-term issues. These long-term issues from using 5-AR inhibitors are collective known as post-finasteride syndrome (PFS), and class-action lawsuits have already been launched against pharma companies for deliberately concealing the side effects of such drugs, which were apparently known even during their development.

    Now, another study demonstrates the crucial role of DHT not only in psychological and sexual health but also the very developmental fields that maintain the structure of the organism and give a living being its unique shape and behavior (phenotype). The study below demonstrates that exposure of snails to the 5-AR inhibitors finasteride and dutasteride dramatically disrupted the development of the snail's shape as well as the viability of its embryos. Exposure to either drug resulted in uncoiled (banana-shape) instead of spiral (ram horns) shell shapes. The concentrations of the two drugs used was rather low and easily achievable by commonly prescribed doses of those drugs. Exposure to a slew of other steroidogenic inhibitors, statins, mutagens, or anti-flammatory chemicals did NOT result in shell disruption. This suggests that the morphogenesis function is unique to DHT and other known beneficial steroids such as progesterone, DHEA, testosterone, etc are not involved (much) in maintaining the shape of an organism. This morphogenesis function of DHT is unrelated to sexual effects as the snails do not use DHT for sexual development/reproduction and do not express the androgen receptor (AR) (or any of the other steroid receptors for that matter). That means DHT has potent non-genomic (metabolic?) beneficial effects, through mechanisms which are just starting to be elucidated. What could those mechanisms be? Well, the study suggests that in other, similar types of snails, such disruption of shell shape is often caused by environmental stressors. In other words, DHT may be acting as a cardinal protector from such stressors or the 5-AR inhibitors are a potent type of such stressors. I think it is reasonable to suspect both are true until more is known.

    https://phys.org/news/2019-11-hormone-clue-snail-shells-spiral.html
    "...5-alpha-reductase (5αR) is the enzyme humans use to convert hormones needed to reproduce. Researchers turned off that same enzyme in developing snails and found their snails grew banana-shaped shells instead of spirals. "Normally they look like ramshorn shapes, very tightly curled," said Dr Alice Baynes at Brunel University London. "But here they get very elongated, so something's happening when we disrupt their 5αR". "We're not sure if not having the enzyme stops the shells from curling, or if the curl isn't starting at the right angle. The enzyme is probably converting something into a hormone that helps shell patterning. They just get this really wide-open curl and when they keep growing for longer, their shells actually look like ring donuts." In mammals, 5αR converts the male sex hormone testosterone into the stronger male sex hormone dihydrotestosterone (DHT), an androgen which helps male development and reproduction. Snails and molluscs, like mussels and squid, also have the 5αR enzyme. But research shows that snails do not use either testosterone or DHT for reproductive development. So scientists wanted to discover what snails do use these hormones for."

    "...In a study in Nature's latest Scientific Reports, the team used the drug dutasteride – which treats enlarged prostates – to block 5αR enzymes in growing snail embryos. "We found a surprising effect on snail shell development," said Dr Baynes. "The snail embryos grow elongated 'banana-shaped' shells instead of tightly curled shells". "This disruption to shell shape is not what we might expect in a mammal or a fish, which would be reduced male characteristics or sperm production. Our findings indicate 5αR has an essential role in snails and could lead to a better understanding of hormones and shell development in molluscs. It's an interesting first step."

    Early embryonic exposure of freshwater gastropods to pharmaceutical 5-alpha-reductase inhibitors results in a surprising open-coiled “banana-shaped†shell

    "...In four independent experiments, dutasteride (DUT) induced an elongated banana-shaped shell phenotype in a dose-dependent manner. The average minimum banana-shaped phenotype response (1% of embryos had banana-shaped shell phenotype) was observed at a dose of 10 µg/L, and the average maximum response (89% of embryos had banana-shaped shell phenotype) at the highest tested dose of 160 µg/L DUT. The banana-shaped shell phenotype became significantly elevated compared to the solvent control at 40 µg/L DUT (P < 0.0001) and higher concentrations (Fig. 4). Finasteride (FIN) also induced the banana-shaped phenotype and its effects were also dose-dependent, although it was less potent than DUT, with the average (based on four independent experiments) minimum response (3% banana-shaped) at 300 µg/L and the maximum (82% banana-shaped) at 1520 µg/L (Fig. 4). FIN significantly induced the banana-shaped phenotype at 450 µg/L FIN (P < 0.0001) and above. In both the DUT and FIN experiments, the number of embryos classed as ‘normal’ was inverse to the banana-shaped phenotype and was significantly reduced in a dose-dependent manner. The percentage of other malformations or embryos that died/did not develop remained stable across the experiments and there was no significant effect (P > 0.05) of DUT or FIN concentration for these endpoints."

    "...Eight other compounds, including three other pharmaceutical steroidogenic enzyme inhibitors (Galeterone (GAL); CYP17A1 inhibitor, Trilostane (TRI); 3β-HSD inhibitor, Atorvastatin (ATO); HMG-CoA reductase inhibitor), one 5β-reductase inhibitor (Chenodeoxycholic acid (ChenA)), a mutagen (Benzoquinoline (BENZO)), and an anti-inflammatory chemical (γ-linolenic acid (y-LIN) were tested in the embryonic B. glabrata assay to assess whether the banana-shaped phenotype was specific to 5αR inhibitors, or if it was a general enzyme-inhibition or toxicity effect. None of the other compounds tested elicited the banana-shaped phenotype (Supporting Information Table S4)...Dorsomorphin (DORS) was included as it had previously been reported to induce ‘immature shell-shape’ or cone-shaped (non-coiling) phenotypes in the gastropod Lymnaea stagnalis (at 0.5 and 1 µM, depending on exposure window)47. However, no banana-shaped phenotype or non-coiling embryos were observed in any of the DORSO concentrations we tested (Supporting information Table S3)...In summary, none of the other compounds tested (pharmaceutical enzyme inhibitors or experimental chemicals) induced the banana-shaped phenotype in developing B. glabrata embryos (Supporting information Tables 3). Only the potent pharmaceutical 5αR inhibitors elicited the developmental effect of shell malformation. Which suggests that the 5αR inhibitors were specifically impacting a particular enzyme vital to B. glabrata morphological development."

    "...To test whether the pharmaceutical 5αR inhibited phenotype was species-specific, a small experiment was conducted with a second freshwater gastropod species, Physella acuta. P. acuta embryos were developmentally exposed to solvent control, 100 and 200 µg/L DUT. This experiment induced strikingly similar results to B. glabrata, with 71.2 and 82.6% of the embryos developing the elongated banana-shaped phenotype in the 100 and 200 µg/L DUT respectively (Fig. 5, Supporting information Table S5). Both DUT doses tested produced significant induction (P < 0.0001) of banana-shaped snails compared to the solvent control, with the reciprocal reduction in normal shaped embryos. As seen with B. glabrata no significant effects of DUT dose were found for the number of non-specific malformations (P > 0.9999, P = 0.8770, respectively) or deaths (P = 0.9282, P > 0.9999, respectively)."

    "...A number of gastropods, such as those within the Vermetidae50 and the Caecidae families51 produce shells that are elongated in shape compared to typical coiled gastropod shells. Variation in coiling can also be seen within freshwater gastropods, and there is some debate about whether these curious findings are distinct species or if the unusual shell growth is a sporadic aberrant phenotype52. Recent investigations into a corkscrew-like shell of the typically planispiral-shaped Gyraulus sp., discovered in a remote Tibetan lake, suggest these phenotypes are the result of as-yet-unknown ecological stressor rather than speciation52. "

    "...Here we demonstrate that pharmaceutical 5αR inhibitors induced a strong and highly reproducible phenotypic response in developing B. glabrata and P. acuta embryos that is not associated with toxicity. We have also confirmed that both 5αR homologues identified in B. glabrata are expressed during embryonic development and that antibodies raised against human 5αRs proteins are reactive in B. glabrata embryo extracts; this strongly suggests that pharmaceutical 5αR inhibitors could be acting on B. glabrata 5αR enzymes to cause this phenotypic disruption. In adult B. glabrata, 5αRs transcripts have been detected in mantle tissue32. This is of note as molluscan shells are formed from secretory cells in the mantle21, providing a possible link between 5αR and shell formation."
     
  2. charlie

    charlie The Law & Order Admin

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    Well you can pretty much take it to the bank that if DHT is vilified to the max, then it's gotta be some great stuff.

    #LiberateDHT
     
  3. jdherk

    jdherk Member

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    Haidut, Make a dht supplement :)
     
  4. Inaut

    Inaut Member

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  5. Risingfire

    Risingfire Member

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    I fully believe this. I was in good shape until I took finasteride. My brother and brother are much leaner than me and they consume many more calories.

    @haidut when I take DHT for more than a few days, I feel like a zombie. Do you think you should take it with other hormones? I've taken it with thyroid and I wake up in the middle of the night with adrenaline surging. Any suggestions?
     
  6. lampofred

    lampofred Member

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    Haven't read the full study but this doesn't seem to be the result from blocking DHT specifically, only from blocking 5ar. Doesn't 5ar convert many other hormones besides just testosterone into DHT? It converts progesterone into dihydroprogesterone for example.
     
  7. OP
    haidut

    haidut Member

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    True, but they tested other steroid synthesis inhibitors that prevent synthesis of progesterone so if the effects was from decreased allopregnanolone or a 5-AR metabolite of cortisol (itself a metabolite of progesterone) and the effects were not explicated. So, it is either a non genomic effect of DHT (as mollusks apparently do not have androgen receptors) or something about the 5-AR itself that is vital for morphogenesis.
    It would have been great if they tried to reverse the uncoiling by administering DHT as that would have confirmed its role, but for some reason they did not do that experiment. I already emailed the authors asking them if they think DHT is the key player or something else related to 5-AR.
     
  8. OP
    haidut

    haidut Member

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    Endpoint steroids are known to lower levels of precursors such as pregnenolone and progesterone, which could affect the GABA system in a negative way. So, as I mentioned in several other threads over the years, adding some pregnenolone or progesterone when using DHT is probably a good idea. Peat also suggested that to people who asked about supplementing with T or Proviron.
     
  9. Hairfedup

    Hairfedup Member

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    Let's all eat sorghum baby!
     
  10. Risingfire

    Risingfire Member

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    Thank you
     
  11. DrJ

    DrJ Member

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    It seems to me like the banana-shaped shells are actually shells that were trying to keep growing (long and straight-ish), while the spiral shells have a growth rate that has been throttled. Similar to how Ray says that fast-growing hair grows long and straight, and slow growing hair is curly. I would take these results from snails and other effects of DHT to suspect that DHT is really a 'growth-ending' or 'growth-inhibiting' hormone, like for hair. A hormone of aging and stress that kicks in to throttle growth when the energy required for the growth becomes too much relative to that available. I would wonder if the banana-shaped shells came out thinner or with some other quality defects(s).
     
  12. Jake sullivan

    Jake sullivan Member

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    Has the reason for this been understood yet? It seems strange knowing how the body seems to have such a high affinity for these protective hormones, would it be the DHT itself downregulating the production of lower chain hormones? Or something that DHT is partially converting into heavily that has this effect that would normally be balanced with the other hormones? Alot of people talk about gonadal suppression/testosterone suppression from DHT, and DHT can partially be converted into androstanediol which apparently has some pro estrogenic effects (however largely offset by the protective effects of DHT) however this androstanediol could be responsible for the inhibition of things like 17-b HSD which i think either you or someone else mentioned in one of the threads i saw recently. I think alot of people would get this idea that DHT is bad because it downregulates precursor hormones but it always seemed strange to me to think something so protective would have drastic side effects, it’s an interesting topic and if you and Danny ever get around to it, i’d love to hear some discussion about that topic on the podcasts, im convinced it might not be DHT having this effect, but largely maybe its partial conversion to androstandione (which would normally be balanced by other hormones)

    Then theres the general concept that the precursor hormones at the bottom of the chain can be taken in really high doses with almost no negative alteration of the hormonal profile such as pregnenolone, but it seems the further down the chain you go, the more you need to balance the precursors, it’d be an interesting topic for discussion

    Personally i find androsterone so far to the most effective broadspectrum potent substance ive ever used for mood issues, anxiety, depression, and relaxation and all around everything, next to progesterone i find androsterone to be my personal favorite, and a large amount of that androsterone is serving as substrate for DHT and so im assuming im largely feeling alot of the effects of increased DHT synthesis, ive never noticed any negative results from androsterone, however it would be worth adding some pregnenolone to make sure no interference with libido happens because if people report gonadal suppression with DHT and if thats true, the same is likely happening with androsterone as it is closer to an endpoint hormone, it seems like pregnenolone really is great for serving as a secondary agent to any hormonal supplementation, like you’ve mentioned recently it seems like people really are sleeping on just how great the effects are of simple pregnenolone alone we’re finding out all these new interesting things about it that are useful
     
  13. MitchMitchell

    MitchMitchell Member

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    Lol @snails

    Everyone knows that anti DHT drugs should be avoided as teratogenic anyway.

    The main issue with DHT comes from its poor metabolism into Diols. That’s what’s normal in a healthy individual. Unfortunately people accumulate DHT because of compromised liver functions (low glucuronidation), hypothyroidism etc.

    An Assessment of Testosterone and its Essential Metabolites for Prostate Cancer Risk | Meridian Valley Lab

    vitamin Bs, coconut and olive oil, vitamin A, zinc, and obviously t3 are healthier ways to keep the steroid chain up and running.
     
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