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

The purpose of this study was to test the role of the mineralocorticoid rec eptor (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 spironol actone and a placebo in a randomized, single-blind cross-over order. After treatment, we studied the circadian profiles of ACTH, plasma cortisol and s aliva cortisol. No significant change in ACTH concentrations emerged. Howev er, there were significant increases in circadian minimal (52.4 +/- 26.7 ve rsus 33.3 +/- 14.4 nmol/l), mean (166.2 +/- 24.9 versus 133.0 +/- 18.3 nmol /1), and maximal cortisol concentrations (389.7 +/- 57.7 versus 335.4 +/- 4 5.0 nmol/l). Also, in the diurnal trough, we found an increase in saliva co rtisol concentrations. Compared to young healthy controls, spironolactone t reatment 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.