Neurosteroids
Sex Hormones

Author: Gianpiero Pescarmona
Date: 04/04/2010

Description

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

KeggHMDB
PregnenolonePregnenolone
ProgesteroneProgesterone
5alpha-DHPROG5alpha-DHPROG
3alpha,5alpha-THPROG3alpha,5alpha-THPROG

Enzymes

Kegg enzymeKegg pathway
HSD3B1/3beta-HSDHSD3B1/3beta-HSD
steroid-5-alpha-reductasesteroid-5-alpha-reductase
AKR1C4/3alpha-HSDAKR1C4/3alpha-HSD

Steroid-5-alpha-reductase

Steroid-5-alpha-reductase and autism?

AKR1C4/3alpha-HSD belongs lo the aldo/keto reductase superfamily

more info on W.....

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

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