Androgen Excess Produces Systemic Oxidative Stress and Predisposes to β-Cell Failure | HairLossTalk Forums

Androgen Excess Produces Systemic Oxidative Stress and Predisposes to β-Cell Failure

Discussion in 'Hair Loss and Alopecia Published Studies' started by squeegee, Apr 21, 2013.

  1. squeegee

    squeegee Banned

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    [h=2]Abstract[/h]In women, excess production of the male hormone, testosterone (T), is accompanied by insulin resistance. However, hyperandrogenemia is also associated with β-cell dysfunction and type 2 diabetes raising the possibility that androgen receptor (AR) activation predisposes to β-cell failure. Here, we tested the hypothesis that excess AR activation produces systemic oxidative stress thereby contributing to β-cell failure. We used normal female mice (CF) and mice with androgen resistance by testicular feminization (Tfm). These mice were exposed to androgen excess and a β-cell stress induced by streptozotocin (STZ). We find that following exposure to T, or the selective AR-agonist dehydrotestosterone (DHT), CF mice challenged with STZ, which are normally protected, are prone to β-cell failure and insulin-deficient diabetes. Conversely, T-induced predisposition to β-cell failure is abolished in Tfm mice. We do not observe any proapoptotic effect of DHT alone or in the presence of H[SUB]2[/SUB]O[SUB]2[/SUB] in cultured mouse and human islets. However, we observe that exposure of CF mice to T or DHT provokes systemic oxidative stress, which is eliminated in Tfm mice. This work has significance for hyperandrogenic women; excess activation of AR by testosterone may provoke systemic oxidative stress. In the presence of a prior β-cell stress, this may predispose to β-cell failure.

    http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011302
     

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