Diurnal changes in glucocorticoid sensitivity in human peripheral blood samples

The secretion of cortisol, a principle homeostatic regulator in humans, shows a circadian rhythm, with high concentrations in the morning and low levels in the evening and at night. Tissue response to hormones is dependent on hormone concentrations but alsb on a variety of cellular factors, such as hormone receptors, transcription factors, and activators. In this report, we evaluated whether cell sensitivity to glucocorticoids (GCs) is also subject to diurnal variation using a whole cell system (whole blood samples) stimulated by lipopolysacharide to induce the production of tumor necrosis factor (TNF-alpha); the induction of TNF-alpha is inhibited by dexamethasone. Blood samples obtained in the morning (08.30-09.00 h) and in the evening (22.30-23.00 h) from 37 healthy individuals (18 males, 19 females) aged 29 +/- 3 years were treated with lipopolysacharide in the presence or absence of 10(-6) M dexamethasone, and the percentage of inhibition of TNF-alpha production was used as an index of sensitivity to GCs. The mean +/- SD in morning samples was 43.5 +/- 13.8% for the general population, 42.3 +/- 14.0% for males and 44.6 +/- 13.8% for females, whereas that in the evening samples was 36.5 +/- 15.7%, 35.6 +/- 13.8% and 37.4 +/- 17.7%, respectively. The results support a significantly increased sensitivity to GCs in the morning hours compared with that in the evening in the general population (P < 0.001) as well as in males (P < 0.001) and in females (P < 0.001). No sex related differences in sensitivity to GCs were observed in the morning or in the evening hours. The sensitive and reproducible assay utilized in this study could also be used to investigate the sensitivity to GCs in various diseases characterized by resistance to GCs and/or alterations in glucocorticoid receptor function. (C) 2000 Elsevier Science Inc. All rights reserved.