Functional regulation of steroid receptors by phosphorylation and redox potential

GALIGNIANA MD

Current Topics in Steroid Research

Research Trends

Año: 2000; p. 1 - 22

Adrenocorticosteroid receptors such the glucocorticoid receptor (GR) or the mineralocorticoid receptor (MR) are primarily localized in the cytoplasm of target cells in association with the 90-kDa heat-shock protein, hsp90. After the discovery of receptor binding to hsp90, it was thought that dissociation of hsp90 from steroid receptors may account for loss of steroid-binding activity as well as acquisition of DNA-binding activity. Today we know that such association with the hsp90-based chaperone system is a sine qua non requirement for these receptors to acquire a steroid binding conformation, as well as to repress transcriptional activity. Upon steroid binding, cytoplasmic receptors must translocate into the nucleus and bind cognate DNA-binding sequences to trigger specific biological responses. Along this pathway, corticosteroid receptors undergo phosphorylation and/or dephosphorylation. It is thought that these processes may regulate not only transcriptional activity, but also the translocation of the steroid-receptor complex into the nucleus. An additional variable that also exhibits dramatic effects on the normal function of the steroid receptors is the redox potential of the cell. It has been well established that, like most of the other members of the steroid receptor family, both the MR and the GR possess cysteine groups that are essential for ligand binding and, consequently, to initiate the specific biological action. Accordingly, differential sensitivity to the redox milieu has been reported for both receptors. In this article I analyze recent advances on both regulatory mechanisms and discuss future perspectives related to the potential of these properties for pharmacological approaches that permit the regulation of specific steroid-dependent biological responses.