Diurnal changes in glucocorticoid sensitivity in human peripheral blood samples

Area of Science:

• Endocrinology
• Chronobiology
• Immunology

Background:

• Cortisol, a key regulator of homeostasis, exhibits a distinct circadian rhythm.
• Tissue response to hormones depends on concentration and cellular factors like receptors and transcription factors.
• Diurnal variations in cellular sensitivity to hormones, including glucocorticoids (GCs), are not fully understood.

Purpose of the Study:

• To investigate whether cell sensitivity to glucocorticoids (GCs) demonstrates diurnal variation.
• To establish a sensitive and reproducible assay for assessing GC sensitivity.

Main Methods:

• Whole blood samples from 37 healthy individuals (males and females) were collected in the morning and evening.
• Lipopolysaccharide (LPS) was used to stimulate tumor necrosis factor-alpha (TNF-alpha) production.
• The percentage of TNF-alpha inhibition by dexamethasone (a GC) indicated GC sensitivity.

Main Results:

• A significantly higher sensitivity to GCs was observed in morning blood samples compared to evening samples (P<0.001).
• This diurnal variation in GC sensitivity was consistent across the general population, males, and females.
• No significant sex-based differences in GC sensitivity were detected at either time point.

Conclusions:

• Cellular sensitivity to glucocorticoids exhibits significant diurnal variation, being higher in the morning.
• The developed assay is sensitive and reproducible, suitable for studying GC resistance in various diseases.
• Findings suggest potential implications for optimizing therapeutic strategies based on the body's natural circadian rhythms.