STEROID-HORMONES AND EXCITABILITY IN THE MAMMALIAN BRAIN

Adrenocortical and gonadal steroid hormones can pass the blood-brain b arrier and bind to intracellular receptors in the brain. In addition t o steroid hormones binding to intracellular steroid receptors, metabol ites of these steroids and steroid hormones produced in the brain (neu rosteroids) are thought to bind to membrane recognition sites. Actions mediated by the intracellular receptors are generally delayed in onse t and are of prolonged duration, whereas the hormones binding to membr ane recognition sites induce fast effects. Both fast and delayed actio ns by steroid hormones potentially alter the electrical properties of neuronal membranes and thus the firing patterns of neurons carrying re ceptors for the hormones. We here review the fast and delayed actions by steroid hormones on single cell electrical properties in the mammal ian nervous system. In general, fast effects by corticosteroids-presum ably mediated by membrane receptors-induce inhibitory effects on cellu lar firing, although regional differences seem to exist. Delayed effec ts by corticosteroid hormones via mineralocorticoid receptors serve to maintain or enhance fast transmission in the brain, while modulatory inputs are suppressed. By contrast, corticosteroids acting through glu cocorticoid receptors suppress transmission carried by amino acids, pa rticularly when the activity is elevated in comparison to resting leve l; modulatory inputs are enhanced. Prolonged activation of glucocortic oid receptors can implicate the integrity of neuronal circuits by allo wing considerable influx of calcium ions during depolarization. Of the gonadal hormones, estradiol mainly exerts excitatory actions, in both a rapid and a delayed mode. Progesterone on the other hand is predomi nantly inhibitory, usually with a short delay in onset. The effect of androgens on neuronal excitability has not yet been studied in great d etail. Finally, neurosteroids and A-ring reduced steroids in general i nduce rapid effects on firing patterns, probably by acting on ligand g ated ion channels. The diverse actions of steroid hormones on single c ell activity have consequences for the excitability in local circuits in which these cells participate. This is illustrated in this review f or two processes that depend on circuit rather than single cell functi on, i.e., long term potentiation and epilepsy. The diverging character of steroid hormones with regard to the time frame, space, and nature of their effects is also reflected in the functional processes that ar e linked to the activity of the networks responding to steroids. In th is way steroid hormones add an essentially new aspect to the regulatio n of functional processes in the brain, during physiological condition s but also when networks are implicated during diseases and disorders. Future research on steroid modulation of cellular excitability will g ain considerably from attempts to either link the changed excitability to the underlying molecular events or study the effects on cellular a ctivity in close connection with behavioral functions. (C) 1997 Academ ic Press