MORPHOMETRIC STUDIES OF THE LOCALIZATION OF THE GLUCOCORTICOID RECEPTOR IN MAMMALIAN-CELLS AND OF GLUCOCORTICOID HORMONE-INDUCED EFFECTS

We studied the subcellular distribution of the glucocorticoid receptor (GR) by light microscopy (LM) and confocal laser scanning microscopy (CLSM) in different mammalian cell types. The effect of added glucocor ticoid hormones on GR distribution was investigated by photometric qua ntitation on optical sections obtained by CLSM followed by statistical analysis. In the control interphase cytoplasm, the distribution of GR was fibrillar in some and diffuse in other cell types. Fibrillar GR w as distributed along cytoplasmic microtubules (MTs) with predilection for a subset of MTs. GR was also observed in the centrosomes. Nuclear GR was both diffuse and granular in distribution. During cell division , GR appeared in the mitotic apparatus at ah stages of mitosis. These findings were not fixation-dependent, Glucocorticoid treatment increas ed both the nuclear and cytoplasmic GR signal. However, this was detec table only after precipitating but not cross-linking fixation. There w as both intra- and intercellular GR heterogeneity in the absence and p resence of hormone but no indication of a hormone-induced nuclear tran slocation of GR. We present a hypothetical model of two independent GR populations in the nucleus and cytoplasm, respectively, without any d iscernible ligand-induced nuclear translocation of GR. The extranuclea r GR population may exert effect(s) on site in the cytoplasm without i nvolving nuclear genomic transcription.