Sleep endocrine effects of antigluco- and antimineralocorticoids in healthy males

Abstract

In several mammalian species the responsiveness of brain neurons to corticosteroids is mediated by mineralo- (MR) and glucocorticoid (GR) receptors. These receptors play a key role not only in the endocrine adaptation to stress but also in corticosteroid-induced changes of behavior, including sleep. We further explored the specific physiological role of this binary receptor system in the human brain by studying electroencephalogram (EEG) sleep and changes in plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, and growth hormone from 1800 to 0700 h in a series of investigations in healthy men pretreated the previous evening with the nonselective GR agonist dexamethasone (Dex) and then receiving at 1400 h either placebo, spironolactone (Spi), an MR antagonist, or mifepristone (Mif), a GR antagonist. The Dex-induced suppression of ACTH and cortisol was unaltered after Spi (200 mg) but attenuated by Mif treatment (400 mg). The sleep-associated plasma growth hormone surge was increased by Dex, an effect that remained unchanged by Spi but was reduced by Mif treatment. Pretreatment with Dex did not by itself induce recognizable effects on EEG sleep, but the Dex combination with Spi reduced the amount of rapid-eye-movement (REM) sleep. With Dex plus Mif, both REM sleep and slow wave sleep (SWS) were reduced compared with placebo. The Dex-induced endocrine effects on plasma ACTH, cortisol, and growth hormone concentrations could not be antagonized by Spi, which acts via MRs mainly located in the hippocampus, but were compensated for in part by Mif, which antagonizes GR at the pituitary and in the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)