Effect of psychosocial stress on FKBP5 and NR3C1 gene expression in healthy young men

Abstract

Stress diseases such as affective disorders are often characterized by a disturbed regulation of the hypothalamus-pituitary-adrenocortical (HPA) axis. This dysregulation can be explained by an impaired function of the receptors involved in the HPA-axis regulation, for example, the glucocorticoid receptors (GR). The regulation process of the HPA axis and the GR function are influenced by several genes, for instance by NR3C1 coding for the GR and also by FKBP5, a co-chaperone in the GR-complex. Binder et al. showed that common polymorphisms in FKBP5 are associated with increased FKBP5 protein expression as well as correlation between cortisol levels and peripheral blood FKBP5 mRNA expression . Regarding the effects of FKPB5 genotypes on psychosocial stress reaction, Ising and colleagues tested healthy subjects with the Trier Social Stress Test, a standardized paradigm to induce psychosocial stress . Subjects homozygous for any of the FKBP5 variants showed an incomplete normalization of the stress induced cortisol secretion.Recent studies demonstrated that FKBP5 and NR3C1 are involved in the endocrine stress reaction. Therefore, we expected changes of FKBP5 and NR3C1 mRNA expression in peripheral blood after exposure to a psychosocial stress situation. To address this, we performed a pilot study where we tested six healthy young men without history of psychiatric or severe somatic disorders and applied the trier social stress test (TSST). Before and after two consecutive TSSTs, we took blood samples with a venous catheter in order to measure ACTH and cortisol in plasma and mRNA expression of the candidate genes in peripheral blood. Blood cells were stabilized using PAXgene tubes, and gene expression was processed by qPCR.Briefly after the psychosocial stress the stress hormones ACTH and cortisol increased whereas the reaction to the second TSST was lower suggesting a habituation effect. These endocrine stress responses were followed by an alteration in FKBP5 gene expression, further underlining the importance of this gene for the neuroendocrine stress reaction. NR3C1 mRNA levels did not change after the TSST.Our preliminary data indicate an effect of psychosocial stress on the FKBP5 mRNA levels. Further research with larger samples sizes is required to replicate and extend these results.

Keywords

• HPA axis
• FKBP5
• NR3C1
• gene expression
• stress hormones
• TSST