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Thread: "Too much testosterone kills brain cells "

  1. #1
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    "Too much testosterone kills brain cells "

    WASHINGTON (Reuters) - Too much testosterone can kill brain cells, researchers said on Tuesday in a finding that may help explain why steroid abuse can cause behavior changes like aggressiveness and suicidal tendencies.

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    Tests on brain cells in lab dishes showed that while a little of the male hormone is good, too much of it causes cells to self-destruct in a process similar to that seen in brain illnesses such as Alzheimer's.

    "Too little testosterone is bad, too much is bad but the right amount is perfect," said Barbara Ehrlich of Yale University in Connecticut, who led the study.

    Testosterone is key to the development, differentiation and growth of cells and is produced by both men and women, although men produce about 20 times more of the hormone.

    It can also be abused, and recent scandals have involved athletes who use the hormone, or steroids that turn into testosterone in the body, for an unfair advantage.

    "Other people have shown that high levels of steroid can cause behavioral changes," Ehrlich said in a telephone interview.

    "We can show that when you have high levels of steroids, you have high testosterone and that can destroy the nerve cells. We know that when you lose brain cells you lose function."

    Ehrlich's team tried the same thing with the "female" hormone estrogen, just to be fair.

    "We were surprised, but it actually looks like estrogen is neuroprotective. If anything, there is less cell death in the presence of estrogen," she said.

    Writing in the Journal of Biological Chemistry, Ehrlich and colleagues said their findings meant people should think twice about supplementing with testosterone, even if it does build muscle mass and aid recovery after exercise.

    "These effects of testosterone on neurons will have long term effects on brain function," they wrote.

    "Next time a muscle-bound guy in a sports car cuts you off on the highway, don't get mad -- just take a deep breath and realize that it might not be his fault," Ehrlich said in a statement.

    The cells die via a process called apoptosis, also known as cell suicide or programmed cell death.

    "Apoptosis is an important thing for the brain -- the brain needs to weed out some of the cells. But when it happens too frequently, you lose too many cells and causes problems."

    A similar process is seen in Alzheimer's disease, the most common cause of dementia in the United States, affecting an estimated 4.5 million Americans, and Huntington's disease, another fatal brain illness.

    "Our results suggest that the responses to elevated testosterone can be compared with these pathophysiological conditions," the researchers wrote.

  2. #2
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    ok guess thats why chicks are ALL soooooo much brighter than any guy...lol

  3. #3
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    idont find that report credible at all.. but is it possible that long term steroid use would cause nerve cell death enough to cause real problems.. well, we cant rule that out on present knowledge..

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    an interesting study would be to compare a large group of steroid users (+20 yrs of use) at their old age to controls and see if there indeed would be a correlation with alz's or other similar conditions..

  5. #5
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    being alive kills brain cell-may as well live the life and have the body you want!!!!!!!


    people stay in your homes! dont even think! preserve all your brain cells for old age! thought kills brain cells as well!!!

  6. #6
    "Next time a muscle-bound guy in a sports car cuts you off on the highway, don't get mad -- just take a deep breath and realize that it might not be his fault," Ehrlich said in a statement. - Stereotyping?

    "We can show that when you have high levels of steroids, you have high testosterone and that can destroy the nerve cells. We know that when you lose brain cells you lose function." - Just an ignorant statement, Show me High Lvs of Test with Deca only.

  7. #7
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    Doesnt say a dose does it.

    Drinking to much water can kill you uno....

  8. #8
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    Doesn't say a dose.. .and it's based in vitro.. doesn't exactly translate into actuality

  9. #9
    "Elevated Testosterone Induces Apoptosis in Neuronal Cells*
    Manuel Estrada12, Anurag Varshney1, and Barbara E. Ehrlich3

    From the Departments of Pharmacology and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520

    Testosterone plays a crucial role in neuronal function, but elevated concentrations can have deleterious effects. Here we show that supraphysiological levels of testosterone (micromolar range) initiate the apoptotic cascade. We used three criteria, annexin V labeling, caspase activity, and DNA fragmentation, to determine that apoptotic pathways were activated by testosterone. Micromolar, but not nanomolar, testosterone concentrations increased the response in all three assays of apoptosis. In addition, testosterone induced different concentration-dependent Ca2+ signaling patterns: at low concentrations of testosterone (100 nM), Ca2+ oscillations were produced, whereas high concentrations (1-10 µM) induced a sustained Ca2+ increase. Elevated testosterone concentrations increase cell death, and this effect was abolished in the presence of either inhibitors of caspases or the inositol 1,4,5-trisphosphate receptor (InsP3R)-mediated Ca2+ release. Knockdown of InsP3R type 1 with specific small interfering RNA also abolished the testosterone-induced cell death and the prolonged Ca2+ signals. In contrast, knockdown of InsP3R type 3 modified neither the apoptotic response nor the Ca2+ signals. These results support our hypothesis that elevated testosterone alters InsP3R type 1-mediated intracellular Ca2+ signaling and that the prolonged Ca2+ signals lead to apoptotic cell death. These effects of testosterone on neurons will have long term effects on brain function."


    I'm lazy, but someone should look up the molecular wieght of test and see how many grams/L 1-10 micro molar is. Its possible the concentrations used here are absurd from our stand point. Does anyone shoot enough test to increase their body leves by a hundred fold? I dont know, but if someone did the math im pretty sure the answer is a big fat no. Normal is around 500ng/dl if i remmeber correctly, but it varies from 250-1,250 ng/dl. If no one steps up to the plate ill do it later

  10. #10
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    hmm

    Bricks, I did the math in another post. 1 micromolar is 30,000 ng/deciliter. In addition, that is probably FREE testosterone, which is normally between 14-100 ng/deciliter. I just printed out the original study (sorry, can't link, got it through my university access) and I will examine it closely.

    But I seriously doubt that even 1-2 grams a week would boost free testosterone above 1000 ng/deciliter, still "safe"

    Test has a m/w of 288 btw so you can check it yourself.

  11. #11
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    No wonder why bbers are so dumb.......

  12. #12
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    Considering the average bodybuilder doesn't drink or do recreational drugs, I still think we come out ahead in terms of intellect and brain cells.

    Now.... I'm going to go front load with 3g of test.

  13. #13
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    Science is full of politics now. You can tell this women went into the study to prove steriods were evil. She played with the science until she got the results she wanted. Notice how she seems to be anti man. Claiming steriod users are jerks then adding that estrogen protects the brain.

  14. #14
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    well I think thats a bit of an overstatement.. but what she is guilty of is claming something that has no real proof.. I mean many different drugs in development work well in in vitro studies prove to be useless in humans.. also if what someone here counted is correct the test levels needed to achieve the damage are far bigger than BB can achuieve with their AAS use.. still nothing is ruled out IMO but a pretty provocative statement maybe just to fuel up the crusade against steroids.

  15. #15
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    Quote Originally Posted by Hellmask
    No wonder why bbers are so dumb.......
    That's one of those sterotypes i don't get.

    Like "bodybuilding women are ugly"

    I think it's just that dumb ugly people get drawn to lifting weights

    Present company being an anomoly

  16. #16
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    If Habeed did his math corectly, to achieve the test levels in the experiment, you would need to be taking something like 10-20g of test a week. This is assuming the number given are for total test - if they're for free test, then we're talking 100's of grams of test. Even the crazier pro's aren't getting anywhere close to this.

    We know that testosterone has direct effects on cells. It makes sense that if you essentially bathe cells in test, you're going to very strong effects up to apoptosis.

  17. #17
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    I heared about this on Fox news (American Al-Jezeera).

    I am a sports scientist, so I am interested in the findings. However I need to look at the research. Looks like BS though.

    A few thoughts though:

    "We were surprised, but it actually looks like estrogen is neuroprotective. If anything, there is less cell death in the presence of estrogen,"

    -Of course most steroids make you produce more estrogen - does this counter balance the effect? (sarcastically) - maybe this is a reason to drop the tamoxifen during a cycle!


    "Tests on brain cells in lab dishes"
    :aaok****t

    -This wasn't even a study on living humans. How can you make claims over experiments conducted in petri-dishes (bizzare!)


    "Apoptosis is an important thing for the brain - the brain needs to weed out some of the cells. But when it happens too frequently, you lose too many cells and causes problems."

    "These effects of testosterone on neurons will have long term effects on brain function,"

    Brain cells are being recycled all the time. The study didn't show there was permanent damage. It was not a protracted study and did not follow subject brain states over a prolonged period (during which testosterone would be normalised). It did not show brain regenerating effects on cessation of steroid use (of which we know occurs with other drugs).

    How the hell can they make these claims when they did not test for them- idiots!

    The study did not even measure the effects of other circulating hormones/ brain interactions in LIVING humans, with feedback mechanisms.

    "Next time a muscle-bound guy in a sports car cuts you off on the highway, don't get mad -- just take a deep breath and realize that it might not be his fault," Ehrlich said in a statement.

    What a wanker. It is so called scientist like this that make me sick. He is obviously not profesional making these kind of comments (and a skinny twat). These kind of wild claims (on anything form nutrition to cancer) are made all the time, with thinking being revised or completely reversed due to unsubstantiated so called science. These characters send out PR photos of themselves and contact news agencies in order to try to get exposure, improve personal self estime, to try and attract funding for their dubious endeavours, or just because they are ego-maniacs.

    "A similar process is seen in Alzheimer's disease, the most common cause of dementia in the United States, affecting an estimated 4.5 million Americans, and Huntington's disease, another fatal brain illness."

    This is complete nonsense! - Alzheimers occurs as a result of a build up of plaque in the brain, which inturn restricts blood flow; kills off brain cells and shrinks regions of the brain.

    "Our results suggest that the responses to elevated testosterone can be compared with these pathophysiological conditions,"

    Our results on the effect of testosterone in a petri dish

    - what a buch of total tossers!

    In addition. As someone who has written and papers and done some exercise physiology based lab tests, you will almost always get conflicting results when you look at multiple studies - sometimes giving completely the reverse opinion. Infact you can write papers to make say some kind off nutritional supplent, say, Gingseng look as if it greatly increases cardiovascular performance. You would just have to include the rogue studies that found this (huge numbers do not support such a claim) and exclude others.

    There was no mention of a control being used, or the competence of testers, facilities or environmental factors.

    This is just one study! - The scientific community will only accept something as a truth, if it has reproducable effects in hundreds of studies - even then some will argue.

    I doubt the professionalism of this buch of muppets making stupid statements to the press. They obviously are out to get a bit of glory and 15 minutes of fame.

    I suspect that they started out with the preconcieved idea that this effect would occur. This happens a lot, with testers WANTING an effect to occur. In my experience, you must have no pre-conceived ideas before conducting experiments/assesing data - otherwise it can have an effect on your findings



    O.K. got the paper now;

    Just a few thoughts:

    "Micromolar, but not nanomolar, testosterone concentrations increased the response in all three assays of apoptosis".

    This study was not conducted on living humans. Therefore- they know how much additional testosterone (whether micro or macromolar).


    The abstract quoted:
    Caspase-3-induced truncation of type 1 inositol trisphosphate receptor accelerates apoptotic cell death and induces inositol trisphosphate-independent calcium release during apoptosis.


    However in a Belgian study Inositol 1,4,5-trisphosphate receptor-deficient (IP3RKO) B-lymphocytes were used to investigate the functional relevance of type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) and its cleavage by caspase-3 in apoptosis.

    Interestingly:

    Expression of caspase-3-non-cleavable mutant receptor, however, dramatically slowed down the rate of apoptosis and prevented both Ca2+ overload and secondary necrosis. (Assafa et al. 2004)

    It seems that the brain has a feedback mechanism!

    This could not be tested for in a petri dish!


    whereas high concentrations (1-10 µM) induced a sustained Ca2+ increase.I

    In agreement with Asafa's observations, "caspase inhibitors impeded apoptosis and the associated rise in [Ca2+]i. Both the staurosporine- and B-cell receptor-induced apoptosis and increase in [Ca2+] could be induced in nominally Ca2+-free and serum-free culture media, suggesting that the apoptosis-related rise in [Ca2+] was primarily because of the release from internal stores rather than of influx through the plasma membrane".

    -Internal stores are FINITE, thus the continual release of CA2+ would only be short term (if at all).

    In other words

    (Assefa et al. 2004)


    Elevated testosterone concentrations increase cell death, and this effect was abolished in the presence of either inhibitors of caspases or the inositol 1,4,5-trisphosphate receptor (InsP3R)-mediated Ca2+ release

    Yes, as we have previously established, this is a natural phenomena that occurs in the brain of a LIVING person. You have shown that your findings mean nothing in your own abstract.

    These results support our hypothesis that elevated testosterone alters InsP3R type 1-mediated intracellular Ca2+ signaling and that the prolonged Ca2+ signals lead to apoptotic cell death.

    No they don't - you just said that the effect was "abolished in the presence of inhibitors od capases/inositol 1,4,5-triphosphate (InsP3R)- mediated CA2+ release - this is a natural phenomenon in human brains - the feedback mechanism (via the previously mentioned caspase-3-non-cleavable mutant receptor!)

    I have spent a small amount of time to easily disprove these claims. I can't be bothered to research more, but I'm sure I could uncover a whole host of information which could show this sensationalist crap up.

    This study may be valid ,so as to show short term effects. However the noted feedback mechanism would negate effects in the longterm. There may be a downgrade of the feedback mechanism with prolonged use (those who abuse steroids and do not come off) - but that would have to be substantiated with relevant proof from relevant studies.

    As an aside:

    Actual values of concentrations of testosterone need to be measured in human beings over sustained periods, as it is not known how much testosterone can breach the plasma barrier.


    A BRIEF DECRIPTION OF THE MECHANISM OF BRAIN CELLS:

    A human brain has roughly 10 billion neurons. A neuron or nerve cell processes and transmits information from the nervous system. Neurons (most) comprise
    soma, dendrites, axons and terminals buttons. Neurons are polarised with an electical charge. They contain neucleolus and chromosomes (made up of long strings of DNA). These messenger RNA, assisting protein synthesis.
    Neurons are possitively charged (a mechanism of flowing pottasium ions), and thus retain a negatively charge ions in the cell. When pottasium ions are stimmulated, they cause an influx, thus effecting a possitive charge, or an action potential. After this event, the ions are exchanged at the nodes of Ranvier, with high sodiium concentrations pumping out potassium and sodium ions (sodium-potasium pump). The event occurs in 1/1000th of a second and restores the negative charge.
    I could go into more setail about chemical mechanisms, but it would be getting away from the point. Although it is important to note that Neuro-dilators, neuro modulatos and Hormones are released by the brain.

    Note hormones can stimulate bothe sides of the cell membrane and the cell neucleus. Thus they can alter behaviour - this does not mean that in excess (say in the case of increased testosterone) they KILL brain cells. They attatch to a binding site, like a lock and key mechanism. They "key" being known as a ligand. For this reason and others that I mentioned in relation to caspase-3-non-cleavable mutant receptors, I do not think cell death occurs at all.
    Should there be a disturbance in neural communication, the vesicle of a neuron collapses in on itself and mixes with the cell membrane, leading to the cell later being retrieved and recylced.

    THIS IS LIKELY TO OCCUR.

    The vesicles (that are filled with neurotransmitters) are then readily availiable to be re-used.

    Brain cells use a shuttle system in order to effect more or less receptors for a transmitting signal, aiding neural pathways, via synapse communication, to be formed and to MAINTAIN function (by assisting the creation of other pathways) following cell death (if any).

    Regulatory signals in the brain manage the number of receptors. The recycling of these receptors PREVENT THE WEAKENING OF SYNAPSES THAT OCCUR IN NEURODEGENERATIVE STATES.

    Unlike "drugs" Testosterone does not shut off recycling. As testosterone, as a hormone, is integral in neuronal communication; an increase should INCREASE cellular recycling! Testosterone does not cause any degradation and it does not decrease the activity of the receptors.

  18. #18
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    as I said in another post, excellently put!! Thanks for ur input!!!

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