Sleep-endocrine effects of mifepristone and megestrol acetate in
healthy men.
Wiedemann, Klaus, Christoph J. Lauer, Margarete Hirschmann, Kristina
Knaudt, and Florian Holsboer.
Max Planck Institute of Psychiatry, Clinical Institute,
Kraepelinstrasse 2-10, 80804 Munich, Germany
APStracts 4:0219E, 1997.
Administration of steroid hormones was demonstrated to modulate sleep
-electroencephalogram (EEG) and sleep-associated hormonal secretion in
specific ways. The present study was conducted to compare the effects
of mifepristone (MIF), a mixed glucocorticoid (GR) and progesterone
receptor (PR) antagonist, and megestrol acetate (MEG), a PR agonist.
Nine healthy men were pretreated with either placebo or 200 mg MIF or
320 mg MEG, or a combination of both. Changes in plasma
adrenocorticotropin (ACTH), cortisol, and growth hormone
concentrations were registered every 30 minutes; sleep-EEG recordings
were obtained continuously. Administration of MIF increased the
morning plasma ACTH and cortisol surges, whereas MEG had the opposite
effect. Growth hormone secretion was lowered by MIF pretreatment and
enhanced by MEG. Simultaneous administration of both compounds led to
largely compensated effects. The sleep-EEG changes induced by MIF
were a slight increase in the time awake and a delayed onset of slow
wave sleep. MEG led to a reduction of rapid eye movement sleep.
Simultaneous administration of MIF and MEG showed a synergism in
increasing time awake and shallow sleep: therefore, it may be
concluded that the sleep-EEG effects are mediated by an interaction
of GR and PR in unknown mechanisms.
Received 18 February 1997; accepted in final form 29 September
1997.
APS Manuscript Number E77-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997