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.
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Authors | Danielle M Osborne, Cheryl A Frye |
Journal | Epilepsy & behavior : E&B
(Epilepsy Behav)
Vol. 16
Issue 3
Pg. 411-4
(Nov 2009)
ISSN: 1525-5069 [Electronic] United States |
PMID | 19782646
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Estrogens
- 5-alpha-Dihydroprogesterone
- Cholestenone 5 alpha-Reductase
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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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