The Glucocorticoid Receptor Co-Chaperone FKBP51 in the Adrenal Cortex Is Not Involved in Regulating Hypothalamic–Pituitary–Adrenal Activity in the Mouse

The FK506 binding protein 51 (FKBP51) is a stress-modulating protein implicated in stress-related psychiatric disorders. While FKBP51 has been extensively studied in the brain and other tissues, its role in the adrenal gland, a key part of the stress response, remains unexplored. To investigate Fkbp5 gene expression and FKBP51 function in the adrenal gland, we examined expression in C57Bl/6 male and female mice and generated an adrenal cortex-specific Fkbp5 knockout (AS^Fkbp5−/−). We found Fkbp5 mRNA expression throughout the adrenal gland in both male and female mice. However, deletion of Fkbp5 in the adrenal cortex did not alter basal stress hormone levels or acute restraint stress responses in both sexes and had no effect on chronic social defeat stress responses in male mice. These findings suggest that FKBP51 in the adrenal cortex plays another role than critically mediating acute or chronic social stress responses and highlight the potential for peripheral FKBP51 manipulations in the treatment of stress-related disorders with no off-target effects at the adrenal level.