[Mechanism of action of glucocorticoids: role of lipocortins].

Glucocorticoids have long been used for their antiinflammatory properties, but the mechanism of this antiinflammatory effect has only recently been clarified. It involves 3 steps: 1. activation of a cytoplasmic receptor following binding of the glucocorticoid; 2. binding of the activated receptor at a specific site on nuclear DNA; 3. synthesis of one or more specific lipocortin proteins. The lipocortins inhibit phospholipase A2, one of the first links in the arachidonic cascade and a principal agent in the inflammatory reaction. Other therapeutic effects of the glucocorticoids, such as immunosuppression and regulation of cellular growth and differentiation, seem to involve a similar mechanism: effect on a cellular receptor, then on the genome, and transcription leading to the synthesis of specific proteins. But are these proteins that are synthetized, different, or are they derivatives of the same family, the lipocortins, the properties of which might be modulated according to the nature of the target cell and the pathological conditions?