Progesterone receptor-mediated effects of neuroactive steroids

R Rupprecht, J M Reul, T Trapp, B van Steensel, C Wetzel, K Damm, W Zieglgänsberger, F Holsboer

Research output: Contribution to journalArticle (Academic Journal)

271 Citations (Scopus)

Abstract

Several 3 alpha-hydroxysteroids accumulate in the brain after local synthesis or after metabolization of steroids that are provided by the adrenals. The 3 alpha-hydroxy ring A-reduced pregnane steroids allopregnanolone and tetrahydrodeoxycorticosterone are believed not to interact with intracellular receptors, but enhance GABA-mediated chloride currents. The present study shows that these neuroactive steroids can regulate gene expression via the progesterone receptor. The induction of DNA binding and transcriptional activation of the progesterone receptor requires intracellular oxidation of the neuroactive steroids into progesterone receptor active 5 alpha-pregnane steroids. Thus, at physiological concentrations, these neuroactive steroids regulate neuronal function through their effects on both transmitter-gated ion channels and steroid receptor-regulated gene expression.

Original languageEnglish
Pages (from-to)523-30
Number of pages8
JournalNeuron
Volume11
Issue number3
Publication statusPublished - Sep 1993

Keywords

  • Base Sequence
  • DNA
  • Desoxycorticosterone
  • Gene Expression Regulation
  • Humans
  • Intracellular Membranes
  • Molecular Sequence Data
  • Neurons
  • Oxidation-Reduction
  • Pregnanolone
  • Receptors, Progesterone
  • Steroids
  • Tumor Cells, Cultured

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    Rupprecht, R., Reul, J. M., Trapp, T., van Steensel, B., Wetzel, C., Damm, K., Zieglgänsberger, W., & Holsboer, F. (1993). Progesterone receptor-mediated effects of neuroactive steroids. Neuron, 11(3), 523-30.