Mineralocorticoid and glucocorticoid receptors in the brain. Implications for ion permeability and transmitter systems

Abstract

In this review we have argued that corticosteroid hormones represent an endocrine signal that can influence neuronal communication. The steroids bind to intracellular receptors in the brain, resulting in slow effects that involve gene transcription, but they may also evoke rapid effects via membrane receptors. The signal carried by the corticosteroids is therefore divergent with respect to the dimension of space and time. Within the rat brain, at least two intracellular receptor subtypes, i.e. MRs and GRs, bind corticosterone. The affinity, density and localization of the MRs is different from the GRs, although the actual properties may vary somewhat depending on the condition of the animal. In general, due to the difference in affinity, low corticosteroid levels result in a predominant MR occupation, while higher steroid levels additionally occupy GRs. Recent studies indicate that predominant MR occupation is important for the maintenance of ongoing transmission in certain brain regions and for neuroprotection. By contrast, additional GR occupation (for a limited period of time) results in an attenuation of local excitability; yet, prolonged exposure to high steroid levels may become an endangering condition for neurons. Since predominant MR occupation on the one hand and additional GR occupation on the other hand induce different cellular actions, the ratio of MR/GR occupation is an important factor determining the net effect of corticosteroid hormones in the brain. How coordinated MR- and GR-mediated effects control neuronal communication under various physiological and pathological conditions will be a challenge for future research.