Sleep endocrine effects of the 11-beta-hydroxysteroiddehydrogenase inhibitor metyrapone.
OBJECTIVE
Besides regulating hormone secretion, steroids also modulate sleep architecture in specific ways. To simulate a state of altered glucocorticoid- and mineralocorticoid-receptor occupation, we administered metyrapone, an 11-beta-hydroxylase inhibitor, that blocks adrenal cortisol synthesis and inhibits the 11-beta-hydroxysteroiddehydrogenase type-1 enzyme in the central nervous system and investigated endocrine changes and the sleep electroencephalogram.


METHODS
Each volunteer spent 4 nights in the sleep laboratory, the first of which served to habituate the subject to the conditions in the laboratory. The volunteers underwent 3 trial conditions in random order and in a single-blind design receiving 2 doses of metyrapone (4.5 g or 6.0 g) or placebo on the day before the sleep electroencephalogram recordings.


METHODS
Sleep laboratory.


METHODS
8 healthy male volunteers.


RESULTS
The corticotropin secretion was significantly enhanced by metyrapone, while the cortisol secretion remained largely unchanged. Growth hormone, progesterone, and dehydroepiandrosterone concentrations were also significantly increased by both doses. Metyrapone induced a pronounced reduction in slow-wave sleep and had slight but nonlinear effects upon rapid eye movement sleep. Parameters of sleep quality were not different between groups.


CONCLUSIONS
Metyrapone induces pronounced effects on hormonal secretion and the sleep electroencephalogram. These results are in part comparable to those from experiments with the administration of corticotropin-releasing hormone and with experiments that deplete mineralocorticoid receptors. The findings may be explained by altered steroid synthesis proximal to the enzyme block. Metyrapone exerts not only effects upon adrenocortical steroid synthesis, but also important extra-adrenal effects on central corticosteroid metabolism.
Jahn
Holger
H
Department of Psychiatry and Psychotherapy, University of Hamburg, Hamburg, Germany. jahn@uke.uni-hamburg.de
Kiefer
Falk
F
Schick
Mildred
M
Yassouridis
Alexander
A
Steiger
Axel
A
Kellner
Michael
M
Wiedemann
Klaus
K
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000311:Adrenal Glands / Q000187:drug effects*; D000328:Adult; D000963:Antimetabolites / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004569:Electroencephalography; D006801:Humans; D006854:Hydrocortisone / Q000037:antagonists & inhibitors*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D008797:Metyrapone / Q000008:administration & dosage / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011374:Progesterone / Q000037:antagonists & inhibitors*; D016037:Single-Blind Method; D012895:Sleep, REM / Q000187:drug effects*
D000963:Antimetabolites; D011374:Progesterone; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone; D008797:Metyrapone