However, glucocorticoid resistance
or GR[alpha] deficiency with lower GR[alpha] expression in the cytoplasm is a general phenomenon in systemic inflammation when a high dose of glucocorticoids is used for long time, especially in unresolved ARDS.
A study of primates implicated FKBP5 as one of the main determinants of glucocorticoid resistance
. (78) A study in humans examined gene-environment interaction between a risk allele associated with enhanced gene expression and ELS exposure.
In addition, elevated S100A8 and S100A9 cause glucocorticoid resistance
in pediatric acute lymphoblastic leukemia .
in the squirrel monkey is associated with overexpression of the immunophilin FKBP51.
Li, "Abnormal expression and distribution of heat shock protein 90: potential etiologic immunoendocrine mechanism of glucocorticoid resistance
in idiopathic nephrotic syndrome," Clinical and Vaccine Immunology, vol.
Despite numerous studies addressing the mechanisms that mediate the response of lymphoid tumor cells to glucocorticoid therapy the mechanism of glucocorticoid resistance
remain incompletely understood.
Synchrony between the hypothalamic-pituitary-adrenal axis and adrenal function occurs during stressful circumstances.(2) Down-regulation, or reduced activity, of glucocorticoid receptors in depression leads to glucocorticoid resistance
, resulting in hyperactivity of this axis.
The pathway for this appears to be impaired negative feedback regulation of HPA axis function and glucocorticoid resistance
(determined by the dexamethasone suppression test).