Glucocorticoids and glucocorticoid antagonists: Lessons from RU 486

Glucocorticoid antagonists (antiglucocorticoids) prevent the biological effects of glucocorticoids by competing with these hormones for binding to the intracellular glucocorticoid receptor. Until recently, the available antiglucocorticoids were either active only in vitro or weakly active in vivo [reviewed in 1, 2]. This limited their experimental and clinical usefulness. Scientists from Roussel-UCLAF Co, France, reported the first potent glucocorticoid antagonist active in vivo in 1981. It is a steroid compound that became known by the company serial number as RU 38486 or by the simplified version RU 486. The discovery of this prototype glucocorticoid antagonist has allowed reexamination of old questions on the various roles of glucocorticoids in physiology and pathophysiology and the initiation of clinical applications. The purpose of this paper is to review briefly the general concepts on glucocorticoid hormone action and antagonism, and to present the current status of basic and clinical research with RU 486.