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Mild exercise elicits de novo synthesis of hippocampal dihydrotestosterone and enhanced neurogenesis in adult male rats
Author(s) -
Okamoto Masahiro,
Hojo Yasushi,
Inoue Koshiro,
Matsui Takashi,
Lee Min chul,
Kawato Suguru,
Soya Hideaki
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1142.30
Subject(s) - hippocampal formation , endocrinology , dihydrotestosterone , medicine , neurogenesis , flutamide , testosterone (patch) , androgen receptor , chemistry , hippocampus , androgen , hormone , biology , neuroscience , prostate cancer , cancer
We accurately determined the concentrations of hippocampus‐derived androgens and estrogens by employing novel derivatization methods to improve the sensitivity of liquid chromatography with tandem mass spectrometry (LC‐MS/MS), despite that the hormones physiological significance is not well understood. Gonadal hormones modulate adult hippocampal neurogenesis (AHN). Androgens, potent neuroprotective steroids, exert permissive action via their receptors (AR) together with several trophic factors such as BDNF and VEGF. These allow us to postulate that exercise increases AHN through hippocampal androgen. We examined the modulatory roles of hippocampal androgens in exercise‐induced AHN in male rats. We demonstrate that treadmill running significantly increased AHN in both orchidectomized (ORX) and sham‐operated (Sham) rats. However, exercised‐induced AHN was fully inhibited by flutamide (AR antagonist) in ORX rats (Fig. 1A, B). Analysis of mRNA expression for 5a‐redctases, which converts testosterone into dihydrotestosterone (DHT), and for AR revealed that both increased in the hippocampus with exercise (Fig. 1C, D). Further, a mass‐spectrometric analysis showed that hippocampal DHT was significantly increased, even if circulating androgens were depleted (Fig. 1E, F). This suggests that exercise‐induced AHN mediates through the paracrine role of newly synthesized hippocampal DHT through AR.