Modulatory mechanisms of cyclic AMP-stimulated steroid content in rat brain cortex

Eur J Pharmacol. 1994 Sep 15;269(1):17-24. doi: 10.1016/0922-4106(94)90021-3.


The modulation of cyclic AMP dependent neurosteroidogenesis was studied in minces prepared from the cerebral cortex of adult rat. Forskolin or dibutyryl-cyclic AMP enhanced pregnenolone and progesterone production in a time and dose-dependent manner. The forskolin effect was mimicked by the cyclic AMP phosphodiesterase inhibitor isobutyl-methyl-xanthine, but not by the adenylate cyclase inactive forskolin analogue 1,9,dideoxy-forskolin. 4'-Chloro-diazepam, a high affinity ligand for the mitochondrial diazepam binding inhibitor (DBI) receptor, also elicited a time dependent increase in steroidogenesis. The forskolin and the 4'-chloro-diazepam stimulated pregnenolone increase was prevented by preexposing the rat brain cortical minces to 1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinoline carboxamide (PK 11195), a high affinity ligand for the mitochondrial DBI receptor endowed with antagonistic properties. The protein synthesis inhibitor cycloheximide prevented the forskolin and 4'-chloro-diazepam stimulation of pregnenolone formation. In brain cortical minces of adrenalectomised/orchiectomised rats dibutyryl-cyclic AMP increased both pregnenolone and progesterone formation, while forskolin only increased progesterone. These data show that cyclic AMP enhances brain steroidogenesis by acting on a labile protein substrate which interacts with the mitochondrial DBI receptor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Adrenalectomy
  • Animals
  • Benzodiazepinones / antagonists & inhibitors
  • Benzodiazepinones / pharmacology
  • Bucladesine / pharmacology*
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Colforsin / analogs & derivatives
  • Colforsin / antagonists & inhibitors
  • Colforsin / pharmacology*
  • Cyclic AMP / metabolism
  • Cycloheximide / pharmacology
  • Dose-Response Relationship, Drug
  • In Vitro Techniques
  • Isoquinolines / pharmacology
  • Male
  • Orchiectomy
  • Pregnenolone / metabolism*
  • Progesterone / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cytoplasmic and Nuclear / drug effects
  • Receptors, Cytoplasmic and Nuclear / metabolism


  • Benzodiazepinones
  • Isoquinolines
  • Receptors, Cytoplasmic and Nuclear
  • diazepam-binding inhibitor receptor
  • Colforsin
  • 4'-chlorodiazepam
  • Progesterone
  • Bucladesine
  • Pregnenolone
  • Cycloheximide
  • Cyclic AMP
  • 1,9-dideoxyforskolin
  • 1-Methyl-3-isobutylxanthine
  • PK 11195