Tuesday, September 25, 2012

Male sex hormones alter the brain after exercise.

Numerous experiments have shown that exercise enhances our ability to remember and think, and causes formation of new nerve cells. A collaboration that includes McEwen's Laboratory of Neuroendocrinology at Rockefeller now shows (in rats) that brain (not gonadal) production of the testosterone derivative dihydroxtestosterone (DHT) is required for this effect. The amount of exercise required is quite mild (McEwen: "the equivalent of jogging at a pace at which someone could speak (or squeak) to a companion."). In castrated rats blocking the action of testosterone levels that have been enhanced by exercise (by blocking testosterone receptors in the brain) also blocks the formation of new nerve cells. The chemical details are given by their abstract:
Mild exercise activates hippocampal neurons through the glutamatergic pathway and also promotes adult hippocampal neurogenesis (AHN). We hypothesized that such exercise could enhance local androgen synthesis and cause AHN because hippocampal steroid synthesis is facilitated by activated neurons via N-methyl-D-aspartate receptors. Here we addressed this question using a mild-intense treadmill running model that has been shown to be a potent AHN stimulator. A mass-spectrometric analysis demonstrated that hippocampal dihydrotestosterone increased significantly, whereas testosterone levels did not increase significantly after 2 wk of treadmill running in both orchidectomized (ORX) and sham castrated (Sham) male rats. Furthermore, analysis of mRNA expression for the two isoforms of 5α-reductases (srd5a1, srd5a2) and for androgen receptor (AR) revealed that both increased in the hippocampus after exercise, even in ORX rats. All rats were injected twice with 5′-bromo-2′deoxyuridine (50 mg/kg body weight, i.p.) on the day before training. Mild exercise significantly increased AHN in both ORX and Sham rats. Moreover, the increase of doublecortin or 5′-bromo-2′deoxyuridine/NeuN-positive cells in ORX rats was blocked by s.c. flutamide, an AR antagonist. It was also found that application of an estrogen receptor antagonist, tamoxifen, did not suppress exercise-induced AHN. These results support the hypothesis that, in male animals, mild exercise enhances hippocampal synthesis of dihydrotestosterone and increases AHN via androgenenic mediation.
In commenting on this work in the NYTimes, Gretchen Reynolds raises an interesting question for women:
But while those findings may be salutary for men who are active and fit, or planning to become so, they seem potentially troubling for those of us without testes. If DHT is necessary for neurogenesis after exercise and women produce far less of it than men, do women gain less brain benefit from exercise than men?


  1. Hmmm... so physical exercise helps us achieve greater mental ability? That's nice to know.

  2. Great article Deric! And yes, physical exercise is always good for our brain. That's nothing new Kurt.