Cortisol resistance in the New World revisited.

Insights into the molecular basis of glucocorticoid action have been obtained from the analysis of cortisol resistance. The glucocorticoid receptor (GR) in both New World primates and guinea pigs has a decreased affinity, in vivo, for cortisol; this is achieved by two distinct mechanisms. In the New World primates recent studies have identified a key role for co-chaperones. The amino acids responsible for cortisol resistance in the guinea pig GR lie not in the ligand-binding pocket but on the surface of the receptor. We hypothesize that this region might be the site of interaction between the co-chaperones and the GR, and hence that the resistance occurs through the same mechanism, albeit from opposite sides.