Neuroactive steroids modify neuronal excitability through interaction with neurotransmitter-gated ion channels (non genomic effect). In addition, these steroids may also exert effects on gene expression via intracellular steroid hormone receptors (genomic effect).
The chemical structure of endogenous 5alpha-pregnan-3alpha,21-diol-20-one (3alpha,5alpha-THDOC) and synthetic (alphaxalone, ganaxolone and 3alpha,5alpha-17-phenylandrost-16-en-3-ol, or 17PA) steroids. b | Biosynthesis of GABA (gamma-aminobutyric acid)-modulatory neurosteroids. The pathway for the synthesis of 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THPROG) from cholesterol is shown. Also indicated is the site of action of drugs that have been used to evaluate the influence of endogenous 3alpha,5alpha-THPROG on inhibitory neurotransmission. Steroidogenic acute-regulatory protein (StAR) might interact with the mitochondrial benzodiazepine receptor (MBR) to facilitate the transport of cholesterol across the mitochondrial membrane. 3alpha-HSD, 3alpha-hydroxysteroid dehydrogenase; 3beta-HSD, 3beta-hydroxysteroid dehydrogenase; 5alpha-DHPROG, 5alpha-dihydroprogesterone; P450scc, P450 side-chain cleavage.
Neurosteroids: endogenous regulators of the GABAA receptor 2005
AKR1C4/3alpha-HSD belongs lo the aldo/keto reductase superfamily
Mechanism of Action
Neurosteroids are produced by both neuron and glial cells.
It is usually associated with GABA synthesis
Alcohol withdrawal syndrome: mechanisms, manifestations, and management, 2016
Update on the Neurobiology of Alcohol Withdrawal Seizures, 2005
Diversity of Steroid Hormone Actions on the Brain