Steroid up-regulation of FKBP51 and its role in hormone signaling

FK506 binding protein 51 (FKBP51, FKBP5) functions as a co-chaperone for androgen, glucocorticoid, mineralocorticoid and progesterone receptors. The FKBP51 can act as an important determinant of the responses to steroids, especially to glucocorticoids in stress and mood disorders and androgens in prostate cancer, raising medical and pharmacological interests in the protein and its gene. Recent studies have revealed the molecular mechanisms by which the androgens and the glucocorticoids via their nuclear receptors elicit the robust up-regulation of the FKBP51 gene. Several polymorphisms in the FKBP51 gene have been associated with the mood disorders and differences in glucocorticoid sensitivity. The polymorphisms may contribute to the steroid up-regulation of the FKBP51 and thus influence the regulatory loops in steroid signaling.

► FKBP51 functions as a co-chaperone for androgen, glucocorticoid, mineralocorticoid and progesterone receptors. ► Steroid hormones, excluding estrogens, rapidly up-regulate FKBP51 expression. ► Up-regulation of cellular FKBP51 potentially creates ultra-short feed-back loops in steroid signaling.