Progesterone receptor-mediated effects of neuroactive steroids

  title={Progesterone receptor-mediated effects of neuroactive steroids},
  author={Rainer Rupprecht and Johannes M. H. M. Reul and Thorsten Trapp and Bas van Steensel and Christian H. Wetzel and Klaus Damm and Walter Zieglgänsberger and Florian Holsboer},

The neuropsychopharmacological potential of neuroactive steroids.

  • R. Rupprecht
  • Biology, Medicine
    Journal of psychiatric research
  • 1997

Neurosteroids: Molecular mechanisms of action and psychopharmacological significance

Functional antagonism of gonadal steroids at the 5-hydroxytryptamine type 3 receptor.

The present study shows that the gonadal steroids, 17beta-estradiol and progesterone, may also act as functional antagonists at the 5-hydroxytryptamine type 3 (5-HT3) receptor in whole-cell voltage-clamp recordings of HEK 293 cells stably expressing the 5 -HT3 receptor.

Steroids, neuroactive steroids and neurosteroids in psychopathology

  • B. Dubrovsky
  • Biology, Medicine
    Progress in Neuro-Psychopharmacology and Biological Psychiatry
  • 2005

Neurosteroids and GABA-A Receptor Function

Molecular mechanisms underlying neurosteroid action on the GABAA-receptor, mood changes, and cognitive functions are described.



Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor.

Two metabolites of the steroid hormones progesterone and deoxycorticosterone are potent barbiturate-like ligands of the gamma-aminobutyric acid (GABA) receptor-chloride ion channel complex and potentiated the inhibitory actions of GABA in cultured rat hippocampal and spinal cord neurons, which may explain the ability of certain steroid hormones to rapidly alter neuronal excitability.

Non-genomic and genomic effects of steroids on neural activity.

  • B. McEwen
  • Biology, Medicine
    Trends in pharmacological sciences
  • 1991

The 5 alpha-reductase in the brain: molecular aspects and relation to brain function.

One of the two major enzymatic systems that transform steroids in the brain is analyzed, namely the 5 alpha-reductase-3 alpha-(3 beta)-hydroxysteroid dehydrogenase pathway, which is widely distributed in practically all CNS structures in all phases of development.

Dopaminergic and ligand-independent activation of steroid hormone receptors.

In vitro, dopamine faithfully mimicked the effect of progesterone by causing a translocation of chicken progestersone receptor (cPR) from cytoplasm to nucleus, and a serine residue in the cPR was identified that is not necessary for progester one-dependent activation of cPR, but is essential for dopamine activation of this receptor.

Characterization of steroid interactions with gamma-aminobutyric acid receptor-gated chloride ion channels: evidence for multiple steroid recognition sites.

Computer-modeling (ALLFIT analysis) of these curves suggests that these steroids and pentobarbital interact with multiple binding sites on GABAA receptor(s) as well as modulating GABA receptor-mediated 36Cl- uptake.

Stress-induced elevations of gamma-aminobutyric acid type A receptor-active steroids in the rat brain.

The presence of allopregnanolone and allotetrahydroDOC in brain is demonstrated and acute stress results in a rapid increase of these neuroactive steroids to levels known to modulate GABAA receptor function.

Synthesis, metabolism, and pharmacological activity of 3 alpha-hydroxy steroids which potentiate GABA-receptor-mediated chloride ion uptake in rat cerebral cortical synaptoneurosomes.

Molecular modeling of the active steroids based on quantitative structure-activity relationships provides evidence to support the stereospecificity of the binding interactions and suggests that there may be more than one type of steroid binding site associated with the GABAA-receptor-mediated chloride ionophore.