The existence of U-shaped dose dependencies has been known for a long time. With regard to corticosteroid action in brain cells, a dual receptor system that works in opposing directions can explain the occurrence of a U-shaped dose dependency. However, recent evidence indicates that many cell- and tissue-specific factors (e.g. the local availability of corticosterone, the expression of receptor variants and the cellular content of other proteins and molecules) also determine the effectiveness of the hormone. This could result in dose dependencies with a different shape, despite the local presence of two receptor types.