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). Many of the enzymes involved in their metabolism are shared by adrenals steroids metabolism.
Neurosteroids and GABAA receptor interactions: a focus on stress, 2011
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
Steroids
Enzymes
Steroid-5-alpha-reductase
Steroid-5-alpha-reductase and autism?
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
Synthesis regulation
Alcohol withdrawal syndrome: mechanisms, manifestations, and management, 2016
Update on the Neurobiology of Alcohol Withdrawal Seizures, 2005
Drugs
Agonists
Antagonists
Diversity of Steroid Hormone Actions on the Brain
Loss of neurosteroid-mediated protection following stress during fetal life
