FKBP51 — a selective modulator of glucocorticoid and androgen sensitivity

FK506-binding protein 51 (FKBP51) is gaining increased recognition for its essential roles in cell biology. Originally discovered as a component of steroid receptor complexes, it is now known to regulate a diverse set of transcription factors, enzymes and structural proteins. Its cellular properties suggest numerous possible functions for FKBP51 in physiology, and the best clue to its potential importance may be the following: FKBP51 is a glucocorticoid-induced negative regulator of the glucocorticoid receptor. Thus, FKBP51 is intricately involved in regulation of the most pleiotropic hormone known to biology. In contrast to glucocorticoid receptor, FKBP51 is a positive regulator of the androgen receptor, suggesting that it functions as a reciprocal modulator of glucocorticoid-mediated and androgen-mediated physiology. In this work, we evaluate this hypothesis by examining recent cellular and physiological evidence.

► FKBP51 is a cochaperone to steroid receptors, including glucocorticoid (GR) and androgen receptors (AR).
► FKBP51 modulates molecular properties of GR and AR, including hormone-binding function.
► Interestingly, FKBP51 exerts negative regulation on GR, but positive regulation of AR.
► The reciprocal modulation of GR and AR by FKBP51 is evaluated based on the most recent in vivo data.