The role of mineralocorticoid receptors in the circadian activity of the human hypothalamus-pituitary-adrenal system: effect of age

Abstract

The purpose of this study was to test the role of the mineralocorticoid receptor (MR) in the circadian activity of the hypothalamus-pituitary-adrenal (HPA) system of elderly healthy subjects. Nine elderly subjects (age: 66.2 +/- 7.7 years) were treated for 8 days with both the MR antagonist spironolactone and a placebo in a randomized, single-blind cross-over order. After treatment, we studied the circadian profiles of ACTH, plasma cortisol and saliva cortisol. No significant change in ACTH concentrations emerged. However, there were significant increases in circadian minimal (52.4 +/- 26.7 versus 33.3 +/- 14.4 nmol/l), mean (166.2 +/- 24.9 versus 133.0 +/- 18.3 nmol/l), and maximal cortisol concentrations (389.7 +/- 57.7 versus 335.4 +/- 45.0 nmol/l). Also, in the diurnal trough, we found an increase in saliva cortisol concentrations. Compared to young healthy controls, spironolactone treatment had stronger effects in the elderly. We therefore conclude that: 1) MR is involved in the human HPA system regulation; 2) the MR participates in the regulation of circadian nadir and peak activity of the HPA system; and 3) the HPA system in the elderly is more vulnerable to dysregulation at the level of the MR.