Effects of androsterone on convulsions in various seizure models in mice

Abstract

It is believed that a deficiency of androgens, including free testosterone, may promote the development of convulsions. The present study revealed differences in the action of androsterone (AND), a major excreted metabolite of testosterone and a neurosteroid, in three commonly used seizure models in mice. AND administered intraperitoneally exhibited dose-dependent protection against tonic-clonic convulsions caused by maximal electroshock (MES) with ED(50) (effective dose(50)) of 227 mg/kg. The compound also inhibited the convulsive action of pentylenetetrazole (PTZ), increasing its CD(50) (convulsive dose(50)) for clonic convulsions from 77.2 (PTZ + saline) to 93.9 (p < 0.05) for PTZ + AND 40 mg/kg and 113.9 mg/kg (p < 0.001) for PTZ + AND 60 mg/kg. In mice pretreated with 60 mg/kg AND, the CD(50) for PTZ-induced tonic convulsions increased from 102 to 127.6 mg/kg (p < 0.01). Surprisingly, doses of 50 and 100 mg/kg AND lowered the CD(50) for kainate (KA)-induced convulsions from 40.8 to 28.7 (p < 0.05) and 25.4 mg/kg (p < 0.001), respectively. In summary, for two of the mouse seizure models, our findings confirmed previous studies that demonstrated protective activity of AND. However, the potentiation of KA-induced convulsions by AND was somewhat unexpected and suggested that AND may also possess proconvulsant activity.

Seizure‐precipitating factors in dogs with idiopathic epilepsy

“…Somewhat related, the influence of male sex hormones on seizures is not well understood. Studies have shown that androgens have an anticonvulsant activity, although some studies have reported conflicting results, whereby testosterone increased the frequency and severity of seizures . Independent of sex hormones, exposure to females in estrus may cause stress in male dogs, which could also explain its ability to precipitate seizures.…”

Effect of Androsterone after Pilocarpine-induced Status Epilepticus in Mice

“…Neurosteroids rapidly alter neuronal excitability through interaction with neurotransmittergated ion channels of GABA A receptors 1,2. In addition, neurosteroids may also exert effects on gene expression via intracellular steroid hormone receptors.…”