Autoradiographic study of the nuclear transfer of the antiglucocorticoid compound RU38486 in mouse tissues

In order to investigate the mode of action of RU38486, a recently described antiglucocorticoid molecule, we have studied by autoradiography the localization of [3H]RU38486 in various glucocorticoid target tissues 30 and 60 min following in vivo injection. The results obtained in brain, liver and kidney sections clearly demonstrate that [3H]RU38486 is specifically translocated in target cell nuclei. Indeed, the nuclear labelling observed after injection of the tracer was significantly decreased after injection of [3H]RU38486 in the presence of a 100-fold excess of unlabelled RU38486. The distribution of the specific labelling of RU38486 within the central nervous system was very similar to that previously described for dexamethasone with an accumulation of radioactivity in the cell nuclei of the hypothalamic area of the nucleus arcuatus. Our results thus provide additional evidence for an action of this antiglucocorticoid molecule at the nuclear level.