Recent Advances in Glucocorticoid Receptor Action

Since 1948, hydrocortisone (cortisol), the principal glucocorticoid (GC) of the human adrenal cortex has been successfully used at phar- macological concentrations for the suppression of clinical manifesta- tions of rheumatoid arthritis. Numerous compounds with GC activity have also been developed and used. Fifty years after their initial clinical use, GCs are still the most im- portant and frequently prescribed class of anti-inflammatory drugs for various inflammatory disorders. They are administered either orally, parenterally (intravenous, intramuscular, intrathecal), or topically (cu- taneous, intranasal, pulmonic, rectal). Despite the many beneficial ef- fects of GCs, they also have their limitations and disadvantages that occur with varying prevalence on different organs and after different durations of therapy. These side-effects can range in severity from cos- metic (e.g. telangiectasias, hypertrichosis) to seriously disabling (e.g. induction of glaucoma, diabetes, osteoporosis) or even life-threatening disorders (e.g. gastric haemorrhage). These adverse effects of GCs se- riously handicap their successful use as anti-inflammatory agents. There is therefore a strong need for the development of substances with the anti-inflammatory potency of classical GCs but with reduced side-effects.