The mineralocorticoid receptor agonist, fludrocortisone, inhibits pituitary-adrenal activity in humans after pre-treatment with metyrapone.
Whereas animal studies have shown a clear inhibitory effect of hippocampal mineralocorticoid receptors (MR) on hypothalamic-pituitary-adrenal (HPA) axis activity, investigations in humans revealed equivocal results. To further clarify the influence of MR in HPA activity we studied 10 healthy men during the circadian nadir of HPA activity (14:00 to 21:00) after pre-treatment with 3 g metyrapone to minimize the impact of basal endogenous cortisol secretion. On three separate occasions, in a placebo-controlled design, subjects received in a randomized order either 0.5 mg fludrocortisone p.o. or 0.2 mg aldosterone i.v. or placebo. Fludrocortisone exerted a significant inhibition of ACTH, cortisol and 11-desoxycortisol (p < 0.05), whereas no such effect was observed after aldosterone or placebo. These preliminary data suggest that MR are involved in the inhibition of the HPA axis during the circadian nadir of glucocorticoid concentrations in humans.
Otte
Christian
C
Department of Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. otte@uke.uni-hamburg.de
Jahn
Holger
H
Yassouridis
Alexander
A
Arlt
Josef
J
Stober
Nina
N
Maass
Philip
P
Wiedemann
Klaus
K
Kellner
Michael
M
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000450:Aldosterone / Q000494:pharmacology; D002940:Circadian Rhythm / Q000502:physiology; D003350:Cortodoxone / Q000097:blood; D005438:Fludrocortisone / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D008797:Metyrapone / Q000008:administration & dosage*; D008901:Mineralocorticoids / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000819:agonists*
D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D005438:Fludrocortisone; D003350:Cortodoxone; D006854:Hydrocortisone; D008797:Metyrapone