Influence of proteinase inhibitors on glucocorticoid receptor properties: recent progress and future perspectives.

Abstract

Studies with proteinase inhibitors have shown that these reagents have potent effects on many properties (including binding, inactivation, degradation, and transformation) of the cytosolic glucocorticoid-receptor. Future studies to determine the influence of these inhibitors on purified receptors and in reconstituted systems should prove particularly useful in elucidating the mechanism(s) of proteinase inhibitor action. Such studies should not only clarify the chemical relationship between proteinase inhibitors and the glucocorticoid receptor(s), but should also provide insight into the basic biochemical nature of steroid binding, inactivation, degradation and transformation. If proteinase inhibitors are shown to exert certain effects by depressing the action of specific enzymes (or other receptor modifying factors), these inhibitors should be helpful in further characterizing and purifying these receptor modifying molecules. On the other hand, if the inhibitors are found to directly interact with the glucocorticoid receptor, such an interaction could prove useful in purifying the receptor (such as using inhibitor-linked affinity columns) as well as characterizing specific chemical groups on the receptor. It should be noted that since proteinase inhibitors affect several properties of the glucocorticoid receptor, it is possible that more than one mechanism of inhibitor action may be revealed.