Reducing Estrogen Synthesis Regenerates Thymus Destroyed By Aging

Discussion in 'Scientific Studies' started by haidut, Feb 12, 2018.

  1. haidut

    haidut Member

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    Recently, I posted a thread showing that immune dysfunction (thymus shrinkage) which developed with aging (and excess of PUFA, estrogen, cortisol) explains cancer incidence much better than any genetic model.
    Immune Dysfunction (cortisol/estrogen/PUFA), Not Genetics, Causes Cancer

    The quote from Peat in that thread directly suggest estrogen is one of the main causative factors of thymus destruction. When I emailed the immune/cancer study authors about the role of estrogen in thymus destruction I got a reply saying there is no evidence for that. Well, the study below begs to disagree and shows that aromatase inhibition not only protects the thymus from atrophy during aging but can completely regenerate it to youthful levels. Perhaps more importantly, the study shows that testosterone itself is not damaging to the thymus as countless of studies have claimed in the past. It is the conversion of testosterone to estrogen that causes negative effects on the thymus and spleen. Given that DHT is non-aromatizable and it itself an aromatase inhibitor, I think DHT may be able to achieve the same effects while at the same time improving other aspects of aging such as bone and muscle health. Progesterone should also have similar protective effects, as Peat has mentioned many times.

    Aromatase inhibitors regenerate the thymus in aging male rats - ScienceDirect
    "...The thymus can be regenerated in aging rats by surgical or chemical castration and regeneration is inhibited by testosterone, which may exert this effect, at least in part, through its conversion to estradiol. An attempt has been made to regenerate the thymus in intact aging rats using inhibitors of the aromatase system, in the hope that this maneuver could lead to the use of such chemical intervention in the treatment of immunodeficiency syndromes. Young adult and aging (18-month-old) male rats were orchidectomized under ether anesthesia and 7 days later given s.c. implants of testosterone in silicone elastomer (SILASTIC) tubing. Some rats received testosterone together with a five-fold excess of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD). One group of young intact rats received implants containing 25 mg ATD and group of 18-month-old intact rats received 125 mg ATD or 25 mg of another, more powerful aromatase inhibitor 4-hydroxyandrostenedione (4-OH). On the 28th day after implanting, rats were killed and the thymus, spleen, prostate gland and seminal vesicles removed for weighing and histology. In addition, estrogen receptors were measured in the thymus was enlarged after orchidectomy and greatly restored in aging rats. In aging rats, both aromatase inhibitors restored the thymus, which appeared normal histologically. In addition, ATD enlarged the thymus in young intact animals. Doses of testosterone which restored the accessory sex organs to weights measured in intact rats prevented the effects of orchidectomy on the thymus, and in old rats the effects of testosterone were blocked by ATD in both thymus and spleen. Available cytosolic estrogen receptors were reduced in thymus of testosterone-treated orchidectomized rats, and this effect blocked by ATD, which itself was apparently able to induce estrogen receptors. Receptors could not be detected in thymus from aging rats, but were measureable in cytosols from thymus of orchidectomized or ATD-treated old rats. It is therefore possible to restore the thymus in intact aging rats without recourse to surgical or chemical castration, and such a maneuver may possibly be of use to enhance an immune system weakened by aging or disease."
     
  2. Murtaza

    Murtaza Member

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    would androsterone work if one cant get DHT?
     
  3. aguilaroja

    aguilaroja Member

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    It is very curious that researchers could not cite info about estrogen effects on thymus function. Of course, some researchers can’t be bothered to enter into dialog with thoughtful readers. The literature goes back years.

    Yep, thymus atrophy is arguably a major signpost of decline. Estrogen may drastically impair thymus function, which argues for a more perceptive view of estrogen than as “the primary female sex hormone”.

    Evidence for estradiol-induced apoptosis and dysregulated T cell maturation in the thymus. - PubMed - NCBI
    “…thymocytes were indeed undergoing apoptosis following E2 treatment. Together, our studies suggest for the first time that estrogen may induce thymic atrophy by triggering apoptosis.”

    Changes in the Level of Immunoglobulins and CD4/CD8 Ratio in Young and Aged Mice with Estradiol Deficiency. - PubMed - NCBI
    “Here we compared the differences in immune response between young C57BL/6N mice with surgical or medical variectomy and aged C57BL/6N mice with the common feature of E2 deficiency following Con A stimulation. We observed inverted CD4/CD8 ratios in the aged group and apparent reduced production of serum immunoglobin (Ig)G, IgA, and IgM in the surgical group, whereas changes in immune parameters in the medical group were moderate.”

    Estrogen induces thymic atrophy by eliminating early thymic progenitors and inhibiting proliferation of beta-selected thymocytes. - PubMed - NCBI
    “…daily i.p. injections of the synthetic estrogen 17-beta-estradiol reduce thymus cellularity by 80% over a period of 4-6 days. Although the atrophy is most strikingly observed in the CD4/CD8 double-positive (DP) thymic subset, the loss of thymocytes is not accompanied by a significant increase in thymocyte apoptosis, suggesting that direct killing of cells may not be the dominant means by which estrogens induce thymic atrophy. Instead, we find that estradiol drastically reduces the lineage-negative, Flt3(+)Sca-1(+)c-Kit(+) population in the bone marrow, a population that contains thymic homing progenitors.”

    GPR30 Contributes to Estrogen-Induced Thymic Atrophy

    Cellular mechanism of estrogen-induced thymic involution in wall lizard: caspase-dependent action. - PubMed - NCBI
    E2 was shown to act through genomic pathway, since the receptor antagonist tamoxifen and transcription/translation inhibitors blocked its apoptotic action. Interestingly, the apoptotic effect of E2 was effectively decreased by progesterone.

    Gene expression profiling of 17beta-estradiol and genistein effects on mouse thymus. - PubMed - NCBI
    “We previously reported that the estrogenic soy isoflavone genistein, as well as 17beta-estradiol (E2), could induce thymic involution, but genistein effects were only partially mediated through estrogen receptors.”

    Evidence for estradiol-induced apoptosis and dysregulated T cell maturation in the thymus. - PubMed - NCBI
    “…thymocytes were indeed undergoing apoptosis following E2 treatment. Together, our studies suggest for the first time that estrogen may induce thymic atrophy by triggering apoptosis.”

    Estrogen receptor alpha is necessary in thymic development and estradiol-induced thymic alterations. - PubMed - NCBI
    “in addition to ERalpha, another receptor pathway is involved in estradiol-induced thymic atrophy.”
     
  4. aguilaroja

    aguilaroja Member

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    There is some suggestive evidence for a protective role for progesterone. Of course, other forum threads have discussed issues in augmented progesterone function in male gender.

    Progesterone inhibits glucocorticoid-induced murine thymocyte apoptosis. - PubMed - NCBI
    “Both estrogen and testosterone increased in vitro thymocyte apoptosis. In contrast, progesterone not only inhibited spontaneous in vitro thymocyte apoptosis, but also prevented in vitro glucocorticoid-induced apoptosis. Progesterone administration also suppressed glucocorticoid-induced in vivo thymocyte apoptosis. These results suggest that anti-apoptotic effects of progesterone may influence T cell development and subsequent immune responses.”

    Reshaping of T-lymphocyte compartment in adult prepubertaly ovariectomised rats: a putative role for progesterone deficiency. - PubMed - NCBI
    “Progesterone deficiency affects mainly the CD8+ lymphocyte compartment through increasing thymic CD8+ cell export and upsetting homeostatic regulation within the CD8+ splenocyte pool. These alterations were reversible through progesterone supplementation.”

    Cellular mechanism of estrogen-induced thymic involution in wall lizard: caspase-dependent action. - PubMed - NCBI
    “E2 was shown to act through genomic pathway, since the receptor antagonist tamoxifen and transcription/translation inhibitors blocked its apoptotic action. Interestingly, the apoptotic effect of E2 was effectively decreased by progesterone.”
     
  5. OP
    haidut

    haidut Member

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    Great, thanks for the corroborative links. I will send those over to the author but given his snappy response the first time I doubt he will even reply :):
    It does not matter actually, the evidence is out there for those who want to see it.
     
  6. Mary Pruter

    Mary Pruter Member

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    Off the topic, but I know you're busy with other things. Wanted to let you know my mother passed away Dec 9th and thank you for all your help with her. She ended up falling and hit her head. Doctors said, NO aspirin! Within 3 days she had a massive stroke and lasted 4 more days. I thank you for what you did, I really feel that all the supplements kept her memory going and she never forgot her friends or family member. Once again, Thank you!
     
  7. OP
    haidut

    haidut Member

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    I am so sorry to hear that! In case you think it is worth pursuing - if the stroke was ischemic and the doctor's advice prevented her from getting a (possibly life-saving) dose of aspirin then you may have a very solid standing for legal action.
     
  8. LeeLemonoil

    LeeLemonoil Member

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    LEAF-Conference in New York has a researcher claiming that Thymus-regeneration by supplementing HgH, DHEA and Metformin succesfully rejuvenated 9 male probands.
     
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