Neurosteroid pregnenolone induces sleep-EEG changes in man compatible with inverse agonistic GABAA-receptor modulation

Brain Res. 1993 Jul 2;615(2):267-74. doi: 10.1016/0006-8993(93)90037-n.


The steroid pregnenolone (P) and its sulfate (PS) can accumulate in the central nervous system independent of peripheral sources. Pharmacologically, the sulphated form of P interacts with the GABAA receptor complex, and functional assays show that this steroid behaves as an allosteric GABAA receptor antagonist. The present study explored the effect of a single dose of P upon the sleep-EEG and concurrent secretion of growth hormone and cortisol in male volunteers. P increased the amount of time spent in slow wave sleep and depressed EEG sigma power. Sleep-associated nocturnal cortisol and growth hormone secretion remained unchanged, ruling out the possibility that P exerted its effect via altered regulation of these hormones. Furthermore, results from in vitro studies on the potency of P to activate gene transcription via corticosteroid receptors made a genomic action of P via hormone receptor-sensitive DNA sequences unlikely. We conclude that P acts in a non-genomic fashion at or in the vicinity of the benzodiazepine binding site, modulating allosterically the GABAA receptor like a partial inverse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Androstanols / pharmacology
  • Electroencephalography*
  • Growth Hormone / blood
  • Humans
  • Hydrocortisone / blood
  • Male
  • Pregnenolone / pharmacology*
  • Receptors, GABA-A / physiology*
  • Sleep / drug effects*


  • Androstanols
  • Receptors, GABA-A
  • pregnenolone sulfate
  • Pregnenolone
  • 11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one
  • Growth Hormone
  • Hydrocortisone