ABSTRACT Steroid hormones are known to have a tremendous impact on seizures and might play a prominent role in epileptogenesis. However, little is known about the role of steroid hormones in absence epilepsy. Here we review recently combined electrophysiological, pharmacological and behavioural studies in a genetic absence epilepsy model, rats of the WAG/Rij strain, towards the role of the hypothalamic-pituitary-adrenal (HPA) and the hypothalamic-pituitary-gonadal (HPG) hormonal systems on the susceptibility to absence seizures and the pathogenesis of absence epilepsy. Steroid hormones affect seizures, however, progesterone, administered in the neocortex has opposite effects compared to systemic administration. This outcome is in agreement with the cortical focus theory that assumes a local cortical origin for the typical spike-wave discharges (SWDs). Next, the role of corticosterone, stressors such as footshocks, and the anticipation of stressful events on SWDs is discussed: it seems that all three facilitate the occurrence of absence seizures. Estrogens are not playing a role in the occurrence of SWDs; however progesterone administered systemically, also in physiological concentrations and in contrast to what is often seen in other forms of epilepsy, has proepileptic effects. This is most likely due to the non-genomic effects through an action on classical GABA A receptors. Interestingly, progesterone reduces absence seizures during pregnancy. Finally, it is suggested that the limbic system may exert an extra-cortical remote control of the absence seizures generated in the cortico-thalamo-cortical loop. It is proposed that the effects on seizures are due to chronic changes in ovarian steroid hormonal milieu in the limbic system. This hypothesis provides additional insight on the hormonal regulation of absence epilepsy and helps to understand controversial effects on the relation between steroid hormones and absence seizures.
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