Neuroactive steroids and seizure susceptibility

There is increasing clinical and experimental evidence that hormones, in pa rticular sex steroid hormones, influence neuronal excitability and other br ain functions. The term 'neuroactive steroids' has been coined for steroids that interact with neurotransmitter receptors. One of the best characteriz ed actions of neuroactive steroids is the allosteric modulation of GABA(A)- receptor function via binding to a putative steroid-binding site. Since neu roactive steroids may interact with a variety of other membrane receptors, excitatory as well as inhibitory, they may have an impact on the excitabili ty of specific brain regions. Neuronal excitability is enhanced by estrogen , whereas progesterone and its metabolites exert anticonvulsant effects. Te stosterone and corticosteroids have less consistent effects on seizure susc eptibility. Apart from these particular properties, neuroactive steroids ma y regulate gene expression via progesterone receptors. Based on their molec ular properties, these compounds appear to have a promising therapeutical p rofile for the treatment of different neuropsychiatric diseases including e pilepsy. This review focuses on the effects of neuroactive steroids on neur onal excitability and their putative impact on the physiology of epileptic disorders. (C) 2001 Elsevier Science B.V. All rights reserved.