T Nation

Elevated T. Kills Nerve Cells


Journal of Biological Chemistry 281: 25492-25501 (September 2006)

Elevated testosterone kills nerve cells

New Haven, Conn.–A Yale School of Medicine study shows for the first time that a high level of testosterone, such as that caused by the use of steroids to increase muscle mass or for replacement therapy, can lead to a catastrophic loss of brain cells.

Taking large doses of androgens, or steroids, is known to cause hyperexcitability, a highly aggressive nature, and suicidal tendencies. These behavioral changes could be evidence of alterations in neuronal function caused by the steroids, said the senior author, Barbara Ehrlich, professor of pharmacology and physiology.

“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,” said Ehrlich.

Testosterone is the main male hormone and it plays fundamental roles in development, differentiation, and cellular growth. In neurons, testosterone acts as a neurosteroid and can induce changes at the cellular level, which in turn lead to changes in behavior, mood and memory. Both neuroprotective and neurodegenerative effects of androgens have been reported.

The researchers showed that high levels of testosterone triggered programmed cell death in nerve cells in culture. Cell death, or apoptosis, is critical in many life processes, including development and disease. It is characterized by membrane instability, activation of caspases, which are the executioner proteins in apoptosis, change in membrane potential, and DNA fragmentation.

“In the present study we have demonstrated for the first time that the treatment of neuroblastoma cells with elevated concentrations of testosterone for relatively short periods, six to 12 hours, induces a decrease in cell viability by activation of a cell death program,” Ehrlich said. “Low concentrations of testosterone had no effects on cell viability, whereas at high concentrations the cell viability decreased with incremental increases in hormone concentration.”

The testosterone-induced apoptosis described in this study occurs through overactivation of intracellular Ca2+ signaling pathways. Overstimulation of the apoptotic program in neurons has been associated with several neurological illnesses, such as Alzheimer disease and Huntington disease.

Co-authors include Manuel Estrada, now continuing his work at the University of Chile in Santiago, and Anurag Varshney, now working at Ranbaxy, a drug discovery company in New Delhi, India.

Journal of Biological Chemistry 281: 25492-25501 (September 2006)

[quote]Taking large doses of androgens, or steroids, is known to cause hyperexcitability, a highly aggressive nature, and suicidal tendencies. These behavioral changes could be evidence of alterations in neuronal function caused by the steroids, said the senior author, Barbara Ehrlich, professor of pharmacology and physiology.

“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,” said Ehrlich.[/quote]

What they basically said here is that the physiological effects of depression and anger can induce negative effects on nerve cells. The same thing happens with many other organs, including the heart. Testosterone is both good and bad for the heart. As with nerve cells, it depends on other factors. The testosterone itself isn’t going to cause damage, but can increase the damage that would occur if under poor mental influence.

JC

‘is known to cause hyperexcitability, a highly aggressive nature, and suicidal tendencies’

Their premise is completely false, and more than one study has proven it so, so I don’t put any value into this research at all.

If I am not mistaken - this study was done in a petri dish - not in an actual human.

Junk science starts out with a result, and will create ‘studies’ that prove that result. Ass backwards from real science.

Great fuckin article. You really convinced me to stop taking steroids. You wanna know what kills the most brain cells? me smashing your skull with my fist. Maybe you can offset the damage by cutting of your scrotum and avoiding further brain cell loss from any “excess” testosterone it might produce.

[quote]RoidEnthusiast wrote:
Great fuckin article. You really convinced me to stop taking steroids. You wanna know what kills the most brain cells? me smashing your skull with my fist. Maybe you can offset the damage by cutting of your scrotum and avoiding further brain cell loss from any “excess” testosterone it might produce. [/quote]

Think this might be a bit excessive?

[quote]RoidEnthusiast wrote:
Great fuckin article. You really convinced me to stop taking steroids. You wanna know what kills the most brain cells? me smashing your skull with my fist. Maybe you can offset the damage by cutting of your scrotum and avoiding further brain cell loss from any “excess” testosterone it might produce. [/quote]

you mean steroids cause rage? hahaha…nice post man.

The main reason this won’t ever be considered as even a possibility with me is as follows; I know a few juicers. One is a MD, with a private practice and one of the most intelligent people I have ever met. Another is a chiropractor with more than enough knowledge of health, nutrition and wellness to be a regular contributor to this site. These two are the tip of the iceberg. I do not personally know a dumb, arrogant, juvenille or immature juicer, and I know many personally.

Even on the internet this has merit. P22, AR, Bushy and pretty much everybody are perfectly polite, extremely intelligent, and would seem to be great members of society.

So long story short, next stupid study to debunk.

First of all, this paper was published online July 27th…why is someone reporting on this now? Secondly, I just glanced over the paper so far…a few things jump out. It looks like they did bad statistics–this doesn’t surprise me, most people don’t know what they’re doing with statistics. It looks like one of their major results is supported by a Bonferoni test, but I can’t really tell from what they did if a Bonferoni was called for, nor if they even interpreted the results correctly. I’m not even sure if they’re doing multiple correlations to begin with. The punch line is that if they did their stats wrong (and if I have the time I might be able to figure this out for sure–or someone else can check), their results are wrong.

The math aside, they also basically drowned cell cultures in test. Biochemistry isn’t my speciality, but my intuition is that isn’t quite how test interacts with neurons in the body. Something tells me that test doesn’t just randomly flood the brain, but interacts with specific cell types and specific receptors on those specific cells. Thus, I’m a little perplexed at how you could ever get a flood of test surrounding neurons as in this paper.

Then, in their discussion they site only one paper as support for the fact that test causes “roid rage”, but it is a paper in a forensics journal. I haven’t pulled that ref, but my guess is that the forensics paper is based on correlation–some dead guy who died in a fit of anger had high test levels. Not exactly a lot of scientific backing. They also state that test has been shown to have neuroprotective activity (two citations) and only have one citation for previous work that test kills neurons. So it sounds like either the research is still not definitive one way or another, or, more likely, they were both lazy in doing the literature search and they cherry picked in the lit they did find.

The other thing is that test research doesn’t seem to be anything that their lab has any history of. Lastly, if you look at their website:

Do you trust any of these people to know anything about testosterone?

Ehrlich has an impressive CV and I think she did her Ph.D. under Jared Diamond, so yeah, good stuff. But not a single previous paper on testosterone. So this is probably some politically motivated piece of science to advance some liberal feminist bullshit agenda and she’s got the credentials to get it published and make it sound like it amounts to something. Wouldn’t be the first time an established prof tried to use science politically.

Yet another case of scientific overreach. There is a big, Big, BIG difference between killing some brain cells in a petri dish and extrapolating that into psychopathologic changes in human behavior.

This “scientist” obviously started with the desired conclusion first and then shoehorned the rest of the study into proving it. The fact that she included estrogen (“just to be fair” per the Reuters story) implies that she has an axe to grind against our favorite hormone. Junk science rears it’s ugly head once again.

Jayhawk

[quote]rg73 wrote:
First of all, this paper was published online July 27th…why is someone reporting on this now? [/quote]

This was made a story today on cnn/msnbc earlier today as I saw it while getting ready this morning.

Perhaps they should have tried some other substances found on the shelf at the local grocery store, on their petri dish culture, and evaluated the results on brain cells.

Nicotine
Alcohol

or

Mt. Dew

Well, now that I have gotten well over halfway through my first cycle, have gained about 16 lbs., retained a little water and had some blood pressure problems, I feel like now better than ever I know that “rage” doesn’t exist.
I can be a bit of a hothead at some times, but since I started I might even say that I have been in a BETTER mood than before. Maybe the blockhead cutting me off on the road is just an asshole to begin with?

[quote]fatsuperman wrote:
Perhaps they should have tried some other substances found on the shelf at the local grocery store, on their petri dish culture, and evaluated the results on brain cells.

Nicotine
Alcohol

or

Mt. Dew

[/quote]

Amen! Steroids are beat down because they aren’t a big industry employing lots of people. Yet, they are waaay more healthful than any of the above.
The hypocrisy is mindblowing.

[quote]truthandlife wrote:


Journal of Biological Chemistry 281: 25492-25501 (September 2006)

Elevated testosterone kills nerve cells

New Haven, Conn.–A Yale School of Medicine study shows for the first time that a high level of testosterone, such as that caused by the use of steroids to increase muscle mass or for replacement therapy, can lead to a catastrophic loss of brain cells.

Taking large doses of androgens, or steroids, is known to cause hyperexcitability, a highly aggressive nature, and suicidal tendencies. These behavioral changes could be evidence of alterations in neuronal function caused by the steroids, said the senior author, Barbara Ehrlich, professor of pharmacology and physiology.

“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,” said Ehrlich.

Testosterone is the main male hormone and it plays fundamental roles in development, differentiation, and cellular growth. In neurons, testosterone acts as a neurosteroid and can induce changes at the cellular level, which in turn lead to changes in behavior, mood and memory. Both neuroprotective and neurodegenerative effects of androgens have been reported.

The researchers showed that high levels of testosterone triggered programmed cell death in nerve cells in culture. Cell death, or apoptosis, is critical in many life processes, including development and disease. It is characterized by membrane instability, activation of caspases, which are the executioner proteins in apoptosis, change in membrane potential, and DNA fragmentation.

“In the present study we have demonstrated for the first time that the treatment of neuroblastoma cells with elevated concentrations of testosterone for relatively short periods, six to 12 hours, induces a decrease in cell viability by activation of a cell death program,” Ehrlich said. “Low concentrations of testosterone had no effects on cell viability, whereas at high concentrations the cell viability decreased with incremental increases in hormone concentration.”

The testosterone-induced apoptosis described in this study occurs through overactivation of intracellular Ca2+ signaling pathways. Overstimulation of the apoptotic program in neurons has been associated with several neurological illnesses, such as Alzheimer disease and Huntington disease.

Co-authors include Manuel Estrada, now continuing his work at the University of Chile in Santiago, and Anurag Varshney, now working at Ranbaxy, a drug discovery company in New Delhi, India.

Journal of Biological Chemistry 281: 25492-25501 (September 2006)
[/quote]

As others have pointed out, we always have to remember the many limitations that in vitro data has compared to that of in vivo.

In this case, although I have not read the paper and don’t know if these questions were addressed by the author or not, I’d ask/propose the following:

  1. Are the concentrations used approachable in the human brain? Is enough distributed to the brain?

  2. We have to consider that testosterone is metabolized to estradiol, not to mention a good deal of other steroids which may or may not have neurological effects. There are very basic questions that always needs to be asked any time you’re talking about an in vitro study evaluating only one compound in order to understand the many possible limitations of the data. Has that concentration been confirmed to occur in vivo, in that particular tissue? Is it metabolized to other compounds in the body? How are the parent compound and metabolites distributed? How are they metabolized in those tissues? What are the physiological effects of those metabolites? How much of the parent compound is metabolized and how much remains unchanged?

But seriously folks, you naturally lose around 13,000 brain cells per day. This is not counting environmental factors, such as pollution and alcohol. Some encouraging studies showed administering Selegine, otherwise known as Eldepryl or Deprenyl, as slowing brain cell apoptosis.

This post was flagged by the community and is temporarily hidden.

So I go over to some friends for dinner, older than us, and I have tried to talk this man into looking into TRT and he resists. So over drinks, he hands me the article he saw on the web… DOH!

So the in vitro tests had the T dissolved in alcohol and they killed the cells with that? There had to be some delivery medium.

Or the T stimulated the cells that then found that the medium did not provide the needed nutrients and other factors needed to thrive.

Brain cells are programmed to self terminate when they are find that they are not doing anything. So maybe the T just woke them up to that. Programmed cell death is important. The cells may have been in limbo or zombies.

Maybe if the petri dish was in view of a decent porn flick the cells would have had something useful to live for.