RETINOIDS MODULATE THE BINDING-CAPACITY OF THE GLUCOCORTICOID RECEPTOR AND ITS TRANSLOCATION FROM CYTOSOL TO NUCLEUS IN LIVER-CELLS

The binding capacity (C-max) of the glucocorticoid hormone receptor (GR) was affected by vitamin A status in rat liver. In rats fed on a vitamin A-overloaded diet as well as in rats administered with retinoic acid (RA) there was an increased ratio C-max of nuclear GR (expressed as fmol/mg liver): C-max of cytosolic GR (expressed as fmol/mg liver) while in rats fed on a vitamin A-deficient diet this ratio was decreased. These results suggested that an increased amount of RA, resulting from either metabolization of an increased amount of dietary retinol or RA administration, enhanced the translocation of GR from the cytosolic compartment to the nuclear compartment. Moreover such an increased amount of RA could also induce the observed decreased C-max of the total GR that we observed. These observations were similar to the well known effects of dexamethasone administration on the properties of GR. It is probable that RA, similarly to dexamethasone treatment, induces a dissociation of the tetrameric form of the cytosolic GR and thus enhances translocation of the monomeric form from cytosol to nucleus and also resulting in an increased proteolytic degradation of the receptor.