Increased activity of the hypothalamus-pituitary-adrenal system after treatment with the mineralocorticoid receptor antagonist spironolactone

The hippocampal mineralocorticoid receptor (MR) is critical for the regulat ion of the basal activity of the hypothalamus-pituitary-adrenocortical (HPA ) system. It has been hypothesized that reduced capacity of the hippocampal MR is involved in the HPA-system dysregulation found in depression and agi ng. We applied the combined dexamethasone suppression/corticotropin releasi ng hormone stimulation (DEX/CRH) test to six healthy young females both bef ore and after 12 days of treatment with the MR antagonist spironolactone to assess HPA regulation. Treatment with spironolactone caused a significant increase in post-dexamethasone cortisol concentrations (75.1+/-56.7 vs. 36. 6+/-24.6 nmol/l, p<0.05). Furthermore, we observed a significant rise in pe ak cortisol concentration after additional human CRH (hCRH) application (22 3.6+/-139.1 vs. 126.7+/-73.3 nmol/l, p<0.02). There was no change in ACTH p lasma concentrations. We thus conclude that (1) the MR antagonist spironola ctone affects HPA system regulation as reflected in the DEX/CRH test and (2 ) these findings are in accordance with the assumption that MR dysfunction may underlie HPA-system dysfunction in depression and/or aging. (C) 2000 El sevier Science Ltd. All rights reserved.