테스토스테론의 대사물인 androsterone의 경련억제에 대한 영향

Abstract

Background: Androsterone is one of the major metabolites from testosterone whose clinical importance remains unclear. This study evaluated the effects of androsterone on seizure susceptibility in mouse models of epilepsy. Methods: The efficacy of androsterone (10~200 mg/kg, i.p.) against seizures induced by various GABA receptor antagonists and glutamate receptor agonists was evaluated. Results: Androsterone protected mice against seizures induced by PTZ (pentylenetetrazol), PCX (picrotoxin), and DMCM (methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate) in a dose-dependent manner. Androsterone did not protect against seizures induced by kainic acid, NMDA (N-methyl-D-aspartic acid), or 4-AP (4-aminopyridine) in mice. Conclusions: These results suggest that androsterone exhibits anticonvulsant activity that occurs largely via nongenomic mechanisms. Testosterone-derived androsterone might be an endogenous protective neuroactive steroid in the brain. Key Words: Androsterone, GABA, Seizure, Neuroactive steroid