Imaging of corticosteroid receptors in live cells

Abstract

Adrenal corticosteroids (cortisol in humans or corticosterone (CORT) in rodents) exert numerous effects on the central nervous system that regulates the stress response, mood, learning and memory, and various neuroendocrine functions. CORT actions in the brain are mediated via two receptor systems: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). It has been shown that GR and MR are highly colocalized in the hippocampus. These receptors are mainly distributed in the cytoplasm without hormones and translocated into the nucleus after treatment with hormones to act as transcriptional factors. Thus, the subcellular dynamics of both receptors are one of the most important issues. Given the differential action of MR and GR in the central nervous system, it is of great consequence to clarify how these receptors are trafficked between cytoplasm and nucleus, and their interactions are regulated by hormones and/or other molecules to exert their transcriptional activity. In this chapter, we describe our recent studies of corticosteroid receptor dynamics in living cells focusing on three points: (1) time-lapse imaging of GFP-labeled corticosteroid receptors; (2) intranuclear dynamics of GFP-labeled corticosteroid receptors using the fluorescence recovery after photobleaching technique; and (3) the possibility of heterodimers formation using the fluorescence resonance energy transfer technique. We discuss various factors affecting the dynamics of these receptors. Further, we would like to present the future directions of in vivo molecular imaging of corticosteroid receptors at the whole brain level.