The Antidepressant Mechanism Of Androsterone

Discussion in 'Scientific Studies' started by haidut, Dec 31, 2016.

  1. haidut

    haidut Member

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    There is solid evidence that androgens have potent antidepressant effects in both sexes. However, the mechanism of action of that antidepressant effect has not been fully elucidated yet. On the other hand, it is also well known that chemicals that increase the levels of the so-called brain-derived neurotrophic factor (BDNF) are potent antidepressants, and in fact, a few large pharma companies are working on orally bioavailable formulations of BDNF that can be used for treating both mood and neurodegenerative disorders.
    This study shows that one of the mechanisms behind the antidepressant effects of androsterone is precisely the upregulation of BDNF and other protein synthesis in the brain. In other words, androsterone has anabolic effects in the brain. The study also mentioned estrogen and stress as two factors that decrease BDNF levels, so I wonder if androsterone inhibiting aromatase has something to do with its effects on increasing BDNF and total protein synthesis in the brain. This may also explain the anti-depressant effects of pregnenolone, progesterone, emodin, niacinamide, etc as they all oppose or block the estrogen/cortisol cascade.
    The HED of androsterone used int he study was about 0.05mg/kg daily, for 8 days. That means just 5mg daily androsterone would be sufficient for most people to replicate the dose used in this study.

    Differential gender-related vulnerability to depression induction and converging antidepressant responses in rats. - PubMed - NCBI
    Differential Gender-Related Vulnerability to Depression Induction and Converging Antidepressant Responses in Rats | Journal of Pharmacology and Experimental Therapeutics

    "...Administration of androsterone, an androgen receptor agonist, to female rats for the same duration, on the other hand, eliminated their higher vulnerability to depression induction (Female 11-min-androsterone group: F1,15 = 4.582, p < 0.05, versus female 11-min group; Fig. 1b) and the depression-related cognitive deficits (Fig. 2, b and d), whereas the hormones themselves at the same dose and with the same administration schedule in rats that were not subject to the OSST trials did not have significant impact on the learning and memory (Fig. 2)."

    "...The impact of inhibiting protein synthesis (protein synthesis-dependent synaptic/structural remodeling) on immobility induction was evaluated. Interestingly, the induction of immobility in both sexes and estradiol-induced higher vulnerability in the males were not changed by anisomycin, a specific inhibitor of protein synthesis (Fig. 5), whereas antidepressive effects (imipramine in both sexes and androsterone in females) were dependent on novel protein synthesis because their effects on the mobility did not occur with the coadministration of anisomycin. The magnitudes of immobility over trials thus did not differ in the male (F3,84 = 0.625, p > 0.05) and female groups (F3,84 = 0.387, p > 0.05)."

    "...Whereas the coadministration of anisomycin effectively blocked the antidepressant effects of imipramine in both sexes and androsterone in the females, intracerebroventricular administration of BDNF completely reversed the blockade produced by anisomycin in both sexes [anisomycin + BDNF versus anisomycin in males: (F1,15 = 18.726, p < 0.001) and in females (F1,15 = 17.118, p < 0.001; Fig. 5)]. No significant changes in mobility over trials were observed in BDNF groups of either sex (p > 0.05; Fig. 5). These results are in line with the evidence reported by others that estrous cycle stage- and stress-related hormones decrease the expression of BDNF in the hippocampus and the prefrontal cortex, that antidepressant treatment increases the production of BDNF (Russo-Neustadt et al., 2000), and that central administration of BDNF produces antidepressant-like behavioral effects (Shirayama et al., 2002)."

    "...We directly evaluated whether the OSST-induced decrease in mobility was sensitive to blocking the glucocorticoid receptors in the three one-trial/day OSST. Administration of mifepristone, a glucocorticoid receptor antagonist, eliminated the decrease in mobility in either sex (male 15-min groups: F2,63 = 3.231, p < 0.05; Fig. 4a; female 11-min groups: F2,63 = 3.166, p < 0.05; Fig. 4b), whereas spironolactone, a mineralocorticoid receptor antagonist, was ineffective in both sexes (p> 0.05; Fig. 4)."

    "...It had not been clearly established previously whether female sex hormones may play any role in depression vulnerability and what might be the underlying mechanism if such a role does exist. The gender and estrous differences could result from higher estradiol levels and associated stress-related HPA axis activity in females, most dramatic at proestrous and estrous stages (Miller et al., 2004; Rhodes et al., 2004). The difference in HPA activity has been tracked to circulating estrogen (Burgess and Handa, 1992). Fluctuating activities of estrogen and HPA activities are accompanied by changed activity of neurotrophins, particularly BDNF, which may play a central role in the efficacy of antidepressants (Nestler et al., 2002; Castrén, 2004), synaptic remodeling, and associated neuronal survival/neurogenesis (Santarelli et al., 2003; Sairanen et al., 2005). BDNF mRNA levels in rat hippocampus and prefrontal cortex fluctuate significantly across the estrous cycle stages, reaching their lowest levels during the proestrous stage (Gibbs, 1998) or the estrous stage (Cavus and Duman, 2003) when estrogen levels are the highest. Consistent with these findings, glucocorticoids (e.g., cortisol, corticosterone) suppress BDNF expression. Furthermore, in males, testosterone inhibits the HPA axis by activating central androgen receptors (Handa et al., 1994; Viau, 2002), and BDNF functions as the neuronal survival mediator of testosterone (Rasika et al., 1999)."
     
  2. tca300

    tca300 Member

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    Thanks for the post!
     
  3. DaveFoster

    DaveFoster Member

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    Noopept raises BDNF, but it might be cholinergic.
     
  4. Wagner83

    Wagner83 Member

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  5. DaveFoster

    DaveFoster Member

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    I think noopept might have mixed serotonergic activity. It seems to take away appetite, sex drive, but also clear up vision nicely. Verbal fluency went up as well.
     
  6. haidut

    haidut Member

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    Then you may be thrilled to find that androsterone is also anti-cholinergic :)
    Suppression of the nicotinic acetylcholine response in rat superior cervical ganglionic neurons by steroids. - PubMed - NCBI
    "...Beta-estradiol, androsterone, aldosterone, and 17alpha-estradiol mimicked hydrocortisone in its inhibitory action on ACh-induced currents (I(ACh)). The potency for the inhibitory actions on I(ACh) was as follows: androsterone > beta-estradiol > hydrocortisone > or = aldosterone = 17alpha-estradiol. Cholesterol had no effect on the I(ACh). In conclusion, the structural characteristics of a steroid are thus considered to be necessary to block nicotinic I(ACh) in rat superior cervical ganglionic cells, whereas the cholesterol side chain might disturb the inhibitory action of the steroid skeleton on nAChRs."

    Given the role of anticholinergic effects in reversing learned helplessness, androsterone's anti-depressant effects become even more obvious.
    New Page Title Here
    "...The increase of cholinesterase, the enzyme that destroys acetylcholine, during enrichment, serves to inactivate cholinergic processes. If deprivation does its harm by increasing the activity of the cholinergic system, we should expect that a cholinergic drug might substitute for inescapable stress, as a cause of learned helplessness, and that an anticholinergic drug could cure learned helplessness. Those tests have been done: "Treatment with the anticholinesterase, physostigmine, successfully mimicked the effects of inescapable shock." "The centrally acting anticholinergic scopolamine hydrobromide antagonized the effects of physostigmine, and when administered prior to escape testing antagonized the disruptive effects of previously administered inescapable shock." (Anisman, et al., 1981.)"
     
  7. DaveFoster

    DaveFoster Member

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    Awesome: anti-estrogen, anti-cortisol, anti-prolactin, anti-adrenaline, anti-cholinergic, GABAergic, thryo-mimetic, just amazing. In effect, the anti-prolactin effects should raise dopamine and oppose serotonin.

    16alpha-Bromoepiandrosterone (HE2000) limits non-productive inflammation and stimulates immunity in lungs. - PubMed - NCBI

    "16alpha-Bromoepiandrosterone (HE2000) is a synthetic steroid that limits non-productive inflammation, enhances protective immunity and improves survival in clinical studies of patients with human immunodeficiency virus (HIV), malaria and tuberculosis infections. We now show that HE2000 decreased nitric oxide production by lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Treatment with HE2000 also reduced non-productive inflammation associated with carrageenan-induced pleurisy and LPS-induced lung injury in mice. In the hapten-carrier reporter antigen popliteal lymph node assay, HE2000 increased absolute numbers of lymphocytes, antigen-presenting cells, hapten-specific immunoglobulin (Ig)M antibody-forming cells and shifted the interferon (IFN)-gamma/interleukin (IL)-4 balance towards IFN-gamma production. In the cystic fibrosis transmembrane conductance regulator (CFTR(-/-)) mouse model of acute Pseudomonas aeruginosa infection, treatment with HE2000 consistently reduced bacterial burden in lungs. All HE2000 effects were dose-dependent. In H1N1 infection in mice, HE2000 was safe but not effective as a monotherapy, as treatment did not effect survival. HE2000 reduced mortality related to excessive inflammation and opportunistic lung infections in animals and patients, and this might extend to those with H1N1 influenza infection."

    A derivative bolsters the immune system, defends against endotoxin, and lowers nitric oxide; I wonder if the same effects apply to androsterone.
     
  8. haidut

    haidut Member

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    That derivatives was developed when they saw that epiandrosterone has these effects. So, epiandrosterone, which is the less active version of androsterone had these effects. Androsterone also has some of these effects. You can search Pubmed for "androsterone bacteria". Some studies on T, androsterone and other androgens having strong antibacterial and antiviral properties will pop up.
     
  9. Stryker

    Stryker Member

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    now that you mention it , andro has in opinion all the vision, anxiolytic and increase in holistic thinking like noopept does.... except where noopept basically felt like an anti-androgen for me where after 3 months i completely lost all feeling down there and while it increased my motivation in ways its almost like i didnt have the "balls" to initiate action on that motivation.

    this may seem like abit of an out there comparison but andro feels like pregnenolone mixed with a low dose of dexamp and phenibut with a dulling effect on the mind without zombification like tianeptine.

    it is by far my most favourite of any hormone ive tried :clapping:
     
  10. DaveFoster

    DaveFoster Member

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    That's awesome and makes me want to try it.

    I used noopept while I did ketogenic fasting; my libido was non-existent at times.
     
  11. Stryker

    Stryker Member

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    initially noopept was amazing , i couldnt have said anything bad about it using 10mg twice a day for 90 days but the vendor i was purchasing it from stopped selling it... then maybe 6 months later it was available again and its effects were nothing like the first time and the only positive was the vision.

    it gave me such extreme erectile dysfunction that i couldnt even get it up by myself which was one of the most stressful periods in my life so i discontinued using it and after 4 months i got some activity back,

    i think i might try get some genuine noopept from JSC LEKKO and see if it re creates the effects from my first use... but i dont know i think maybe its one of those things you only need to take very small amounts of for one cycle EVER as i think some of the benefits might be permanent and have a very tight U-curve.

    i would definately recommend andro it has such a wide range of benefits and no downsides that ive experienced, maybe it has changed the smell of my sweat but i cant say in certain . i took a week break over christmas and started back on it again and the way it hardens and dries your body is amazing. Its like an MMA fighter whos just down a massve weight cut through fluid manipulation except without being drained and exhausted:praying::praying:
     
  12. LeeLemonoil

    LeeLemonoil Member

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    I'm sorry for this somewhat off-topic question, but since the anti-cholinerg action of Androsterone is discussed:

    In "Peat-terms/rationale", how is Anti-acetylcholinesterase regarded? A general consensus that inhibition is beneficial?
    Many essential oils are currently researched for neurological actions, especially in regard to Azheimer's D..

    Juniper Anti-Acetylcholinesterase and Antioxidant Activities of Inhaled Juniper Oil on Amyloid Beta (1-42)-Induced Oxidative Stress in the Rat Hippocampus

    but also others like Coriander and Spanish Sage oils, their inhaled volatiles that is, are potent at inhibiting/decreasing ACh

    Wiki article on inhibitory/allosteric GABA-positives Neurosteroids also claims they are "memory- and cognition impairing" - Any thoughts on that, especially given the action on ACh?
    Sorry if these issues have also been adressed somewhere else, too unpatiend to roam the threads just now
     
  13. LeeLemonoil

    LeeLemonoil Member

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  14. DaveFoster

    DaveFoster Member

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    I'm planning on trying it, but I need to be sure I mess my HPA up for life.

    I think you said you take magnesium glycinate chelate spread throughout the day; do you do that because of the GABA effects, and have you tried the milk of magnesia + seltzer water for comparison? I'm looking for a good magnesium supplement.
     
  15. DaveFoster

    DaveFoster Member

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    Not good: acetylcholinesterase breaks down ACh, and that's a good thing.
     
  16. Stryker

    Stryker Member

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    yeah i take "doctor's best" , magnesium lysinate glycinate chelate .. and yeah ive tried the carbonate variants it makes stools abit loose for me , i havnt come to a conclusion on the psychological effects of the chelate yet.
     
  17. LeeLemonoil

    LeeLemonoil Member

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    I can't make sense out of the study Haidut posted. So Androsterone increases ACh or has a similar effect? @DaveFoster
     
  18. haidut

    haidut Member

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    No, androsterone acted as nicotinic acetylcholine (ACh) receptor antagonist. It's in the abstract - the tested steroids acted in a manner opposite to ACh.
     
  19. sladerunner69

    sladerunner69 Member

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    I would caution about suppressing cortisol/estrogen too heavily, noting that most users here are also suppressing this pathway through diet. This has happened to a few user here and also happens with bodybuilders whoa re using clomid and other drugs to supress estradiol. A small amount of estrogen I think is needed for mental clarity and a content relaxed feeling that Im finding hard to articulate but for a while I was incredibly irritable along with painful joints and feet and I blame too low estrogen/cortisol for it. 5-8 drops of androsterone plus just about every other supplement and Peat-approved food will totally abolish this pathway which may be beneficial in some respects but is far from natural and not what the organism and the mind are designed for.
     
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