What is the Origin of Cellular Glucocorticoid Resistance?

The concept stems from observations in clinical endocrinology, initially recognized in rare genetic disorders but increasingly appreciated as a functional state in common chronic conditions like metabolic syndrome and persistent stress. The term highlights a post-receptor defect, emphasizing that the problem lies not with hormone production but with the cell's ability to correctly interpret the hormonal message.

What is the Mechanism of Cellular Glucocorticoid Resistance?

Resistance often involves alterations in the glucocorticoid receptor (GR) itself, such as reduced receptor number, impaired binding affinity, or, most commonly, defects in the nuclear translocation and subsequent gene transcription activity of the receptor-hormone complex. Chronic, high-level exposure to cortisol can lead to receptor downregulation, effectively dampening the cell's response to the hormone and contributing to a persistent pro-inflammatory state that the body attempts to compensate for with further cortisol secretion.

Cellular Glucocorticoid Resistance ∞ Area

Cellular Glucocorticoid Resistance

Meaning

Cellular Glucocorticoid Resistance is a clinical state where target cells exhibit a diminished sensitivity to the biological effects of circulating glucocorticoid hormones, primarily cortisol, despite normal or even elevated hormone concentrations in the bloodstream. This resistance can manifest as a reduced anti-inflammatory effect or an altered metabolic response to stress signaling. It represents a functional disconnect between the endocrine signal and the cellular response, contributing to chronic inflammatory states and HPA axis dysfunction.