BehindTheMedspeak: Can elevated testosterone levels cause brain damage?

Those were the findings of a study published in the September 1, 2006 issue of the Journal of Biological Chemistry.

Scientists from the departments of pharmacology and cellular and molecular physiology at Yale University showed that short periods of elevated testosterone levels (six to 12 hours), such as those resulting from the use of muscle-building steroids, lead to "cell death" and "have long term effects on brain function.

The abstract of the article follows.

Elevated Testosterone Induces Apoptosis in Neuronal Cells

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.

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[via Meaghan Wolff and the Washington Post]