The mineralocorticoid receptor agonist, fludrocortisone, inhibits pituitary-adrenal activity in humans after pre-treatment with metyrapone.

Christian Otte, Holger Jahn, Alexander Yassouridis, Josef Arlt, Nina Stober, Philip Maass, Klaus Wiedemann, Michael Kellner

Department of Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. otte@uke.uni-hamburg.de

Life sciences 2003 Aug 22

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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.

Citation

Christian Otte, Holger Jahn, Alexander Yassouridis, Josef Arlt, Nina Stober, Philip Maass, Klaus Wiedemann, Michael Kellner. The mineralocorticoid receptor agonist, fludrocortisone, inhibits pituitary-adrenal activity in humans after pre-treatment with metyrapone. Life sciences. 2003 Aug 22;73(14):1835-45