GILZ: a new link between the hypothalamic pituitary adrenal axis and rheumatoid arthritis?

The hypothalamic-pituitary-adrenal (HPA) axis is an important regulator of the stress response. In healthy individuals, the HPA axis maintains an equilibrium, ensuring that endogenous glucocorticoid (GC) levels remain within the normal range. However, hypofunction of the HPA axis may have a role in the development of inflammatory diseases, such as rheumatoid arthritis (RA). Glucocorticoid-induced leucine zipper (GILZ) is an anti-inflammatory protein, the expression of which is upregulated by GC. Although GILZ mediates the anti-inflammatory effects of GC, it may not be associated with the adverse effects that are frequently caused by exogenous GC administration. This has raised interest in GILZ potentiation as a therapeutic approach in diseases such as RA, which may mimic the anti-inflammatory effects of GC without causing harmful side effects. This review will outline the involvement of the HPA axis in RA, as a prelude to highlighting emerging evidence regarding the role of GILZ in inflammation control and RA.

GILZ: Glitzing up our understanding of the glucocorticoid receptor in psychopathology.

Dysfunction of the hypothalamic-pituitary-adrenal axis, particularly the glucocorticoid receptor, is a commonly implicated link between stress and psychopathology. GR abnormalities are frequently reported in depression, and these anomalies must be resolved before depressive symptoms remit. This biological finding is rendered clinically relevant by the knowledge that only select antidepressants alter GR function. The relationship between GR dysfunction and other diseases associated with psychiatric stress, such as post-traumatic stress disorder (PTSD) and fibromyalgia, is also documented. However, as laboratory constraints limit the utility of GR testing, other measures of GR activity, such as levels of GR-induced genes, may have greater clinical value. In this review, glucocorticoid-induced leucine zipper (GILZ), a product of GR-initiated gene transcription, will be discussed in the context of GR dysfunction in psychopathology.