SELECTIVE EFFECTS OF 8-BR-CAMP ON AGONISTS AND ANTAGONISTS OF THE GLUCOCORTICOID RECEPTOR

RU486 has been reported to be a glucocorticoid receptor (GR) and a pro gesterone receptor (PR) antagonist. We have analysed RU486 activity on the CR in WCL-2 (CHO) cells and in COS-7 cells transiently transfecte d with the mouse GR and with the reporter MMTVCAT (MCAT). These cell l ines do not contain any active progesterone or androgen receptors. In both cell lines RU486 is a partial agonist of the GR with 10-15% of th e activity of dexamethasone. As expected, RU486 is also a partial anta gonist of the GR. Treatment of COS-7 cells with 8-Br-cAMP increases th e agonist activity of both dexamethasone and RU486. This cAMP induced superactivation is seen with all steroids that have full or partial ag onist activity. In contrast, the activities of ZK98.299 and R5020, whi ch are complete antagonists of the GR without any agonist activity, ar e not affected by 8-Br-cAMP treatment. This effect of 8-Br-cAMP is not seen in WCL2 cells. 8-Br-cAMP, therefore, is not a switch which chang es antagonists to agonists but is, rather, a cell specific activator o f all agonists whether they have full or only partial agonist activity .