Non-genomic glucocorticoid effects to provide the basis for new drug developments

Abstract

Glucocorticoids act via genomic and non-genomic actions. The genomic glucocorticoid actions are well known and new details on processes of transactivation and transrepression have been reported recently. Here we describe the current knowledge on non-genomic glucocorticoid actions and discuss why these actions are considered to be of therapeutic relevance. It is assumed that rapid non-genomic glucocorticoid effects are mediated by three different mechanisms: (1) physicochemical interactions with cellular membranes (non-specific non-genomic effects); (2) membrane-bound glucocorticoid receptor (mGCR)-mediated non-genomic effects; and (3) cytosolic glucocorticoid receptor (cGCR)-mediated non-genomic effects. With regard to the first mechanism, we discuss here lazaroids and the novel development of drug targeting with liposomes as the carrier system for glucocorticoids. The clinical use of the latter two mechanisms is still speculative, but intriguing ideas are being discussed in this regard.