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Estrogen increases latencies to seizures and levels of 5alpha-pregnan-3alpha-ol-20-one in hippocampus of wild-type, but not 5alpha-reductase knockout, mice.

Abstract
Sex steroids can influence seizures. Estrogen (E(2)), progesterone (P(4)), and its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), in particular, have received much attention for exerting these effects. Typically, it is thought that E(2) precipitates seizures, and progestogens, such as P(4) and 3alpha,5alpha-THP, attenuate seizures. However, E(2) may also have antiseizure effects, perhaps in part through its enhancement of the formation of 3alpha,5alpha-THP, which has GABA(A)/benzodiazepine receptor agonist-like actions. To test this hypothesis, male and female, castrated or ovariectomized, wild-type and 5alpha-reductase knockout mice were implanted with Silastic capsules of E(2) or vehicle and then administered pentylenetetrazol (85 mg/kg, ip). Wild-type, but not 5alpha-reductase knockout, mice administered E(2) had significantly longer latencies to myoclonus and increased levels of 3alpha,5alpha-THP in the hippocampus. Thus, some of the anticonvulsive effects of E(2) may involve formation of 3alpha,5alpha-THP in the hippocampus.
AuthorsDanielle M Osborne, Cheryl A Frye
JournalEpilepsy & behavior : E&B (Epilepsy Behav) Vol. 16 Issue 3 Pg. 411-4 (Nov 2009) ISSN: 1525-5069 [Electronic] United States
PMID19782646 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Estrogens
  • 5-alpha-Dihydroprogesterone
  • Cholestenone 5 alpha-Reductase
Topics
  • 5-alpha-Dihydroprogesterone (deficiency, metabolism)
  • Animals
  • Cholestenone 5 alpha-Reductase (genetics)
  • Disease Models, Animal
  • Estrogens (metabolism, pharmacology, therapeutic use)
  • Female
  • Hippocampus (drug effects, metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Reaction Time (drug effects)
  • Seizures (drug therapy, genetics, pathology)

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