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

Epilepsy Behav. 2009 Nov;16(3):418-22. doi: 10.1016/j.yebeh.2009.09.008. Epub 2009 Oct 23.


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 3alpha-androstanediol (3alpha-diol). T, but not 3alpha-diol, binds androgen receptor. We investigated effects of 3alpha-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 3alpha-diol had less seizure activity than those administered vehicle. Flutamide had no effects. T is aromatized to 17beta-estradiol (E(2)), which, like 3alpha-diol, acts at estrogen receptors (ERs). Selective estrogen receptor modulators that favor ERalpha (propyl pyrazole triol, 17alpha-E(2)) or ERbeta (diarylpropionitrile, coumestrol, 3alpha-diol), or both (17beta-E(2)), were administered (0.1 mg/kg, SC) to juvenile male rats 1 hour before pentylenetetrazol. Estrogens with activity at ERbeta, but not those selective for ERalpha, produced antiseizure effects. Actions at ERbeta may underlie some antiseizure effects of T's metabolites.

MeSH terms

  • Analysis of Variance
  • Androgen Antagonists / pharmacology
  • Androstane-3,17-diol / therapeutic use*
  • Animals
  • Anticonvulsants / therapeutic use*
  • Disease Models, Animal
  • Estradiol / therapeutic use*
  • Estrogen Receptor beta / drug effects
  • Estrogen Receptor beta / metabolism*
  • Flutamide / pharmacology
  • Male
  • Pentylenetetrazole / pharmacology
  • Rats
  • Rats, Long-Evans
  • Reaction Time / drug effects
  • Seizures / chemically induced
  • Seizures / prevention & control*


  • Androgen Antagonists
  • Anticonvulsants
  • Estrogen Receptor beta
  • Androstane-3,17-diol
  • Estradiol
  • Flutamide
  • Pentylenetetrazole