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.