Steroid receptor signalling in the brain - Lessons learned from molecular imaging

Studies with green fluorescent protein (GFP) have revealed the subcellular distribution of many steroid hormone receptors to be much more dynamic than previously thought. Fluorescence resonance energy transfer (FRET) and fluorescence recovery after photobleaching (FRAP) are powerful techniques with which to examine protein-protein interaction and the mobility of tagged proteins, respectively. FRET analysis revealed that steroid treatment (with corticosterone or testosterone) induces direct interaction of the glucocorticoid receptor (GR) and importin α in the cytoplasm and that, shortly after nuclear entry, the GR detaches from importin α. The mineralocorticoid receptor (MR) and androgen receptor (AR) show the same trafficking. Upon oestradiol treatment, ERα and ERβ in the same cell are relocalised to form a discrete pattern and are localised in the same discrete cluster (subnuclear foci). FRAP analysis showed that nuclear ERα and ERβ are most dynamic and mobile in the absence of the ligand, and that mobility decreases slightly after ligand treatment. Genomic as well as non-genomic actions of steroid hormones influence the cellular function of target tissues spacio-temporally.