Mineralocorticoid receptor-mediated inhibition of the hypothalamic-pituitary-adrenal axis in aged humans

Introduction: In aged humans, diminished mineralocorticoid receptor (MR) mediated feedback in the brain could contribute to impaired feedback regulation of the hypothalamic-pituitary-adrenal- (HPA)-axis but no study specifically compared young and old individuals with regard to MR function. Methods: We examined 10 healthy young (mean age±SD 26.1±2.9yrs.) and 10 elderly men (68.3±4.7yrs.) next to the nadir of cortisol levels (1400h-2100h) when HPA activity is mainly controlled by MR. After pre-treatment with 3g metyrapone to minimize the impact of basal endogenous cortisol secretion, subjects received in randomized order on two separate occasions either 0.5mg of the MR agonist fludrocortisone or placebo p.o. Results: Fludrocortisone significantly decreased maximum ACTH and cortisol concentrations in both groups. ACTH and cortisol values after fludrocortisone were significantly higher in older compared to young men. Conclusions: Our results implicate that a decrease in MR mediated negative feedback contributes to the diminished feedback activity in older humans.