The animal and cell models that uncovered FKBP51 as a regulator of glucocorticoid receptor function.

Abstract

Many New World primates are glucocorticoid-resistant secondary to expression of low affinity glucocorticoid receptors. We identified the role of FKBP51 in hormone responsiveness by showing that multiple cell lines derived from New World primates share the same activities: (1) soluble cell extracts conferred low binding affinity to high affinity glucocorticoid receptors; (2) FK506 increased receptor binding in soluble cell extracts; and (3) cellular FKBP51 was elevated and FKBP52 was lower. Details of these cell lines and their availability are described. Subsequently, we showed that New World primate and human FKBP51 decreased glucocorticoid activity in heterologous COS-7 cell cultures. Future studies using the FKBP51 antagonist SAFit2 in New World primates are proposed.