Antiseizure effects of 3 alpha-androstanediol and/or 17 beta-estradiol may involve actions at estrogen receptor beta

作者：Frye Cheryl A^*; Ryan Allicia; Rhodes Madeline

来源：Epilepsy and Behavior, 2009, 16(3): 418-422.

DOI：10.1016/j.yebeh.2009.09.008

• Testosterone
• Estrogens
• Androgens
• 3 alpha-Diol
• Androgen receptors
• Ictal activity
• Neurosteroids

Testosterone (T), the principal androgen secreted by the testes, can have antiseizure effects. Some of these effects may be mediated by T's metabolites. T is metabolized to 3 alpha-androstanediol (3 alpha-diol). T, but not 3 alpha-diol, binds androgen receptor. We investigated effects of 3 alpha-diol (1 mg/kg, SC) and/or an androgen receptor blocker (flutamide 10 mg, SC), 1 hour prior to administration of pentylenetetrazol (85 mg/kg, IP). juvenile male rats administered 3 alpha-diol had less seizure activity than those administered vehicle. Flutamide had no effects. T is aromatized to 17 beta-estradiol (E(2)), which, like 3 alpha-diol, acts at estrogen receptors (ERs). Selective estrogen receptor modulators that favor ER alpha (propyl pyrazole triol, 17 alpha-E(2)) or ER beta (diarylpropionitrile, coumestrol, 3 alpha-diol), or both (17 beta-E(2)), were administered (0.1 mg/kg, SC) to juvenile male rats 1 hour before pentylenetetrazol. Estrogens with activity at ER beta, but not those selective for ER alpha, produced antiseizure effects. Actions at ER beta may underlie some antiseizure effects of T's metabolites.

• 出版日期2009-11