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GABAA receptor active steroids are altered in epilepsy patients with tuberous sclerosis
  1. F di Michele1,
  2. M Verdecchia2,
  3. M Dorofeeva4,
  4. L Costamagna3,
  5. G Bernardi2,
  6. P Curatolo2,
  7. E Romeo1
  1. 1Neuroendocrinology Laboratory, IRCCS Santa Lucia, Rome, Italy
  2. 2Department of Neuroscience, Tor Vergata University, Rome
  3. 3Department of Forensic Medicine, La Sapienza University, Rome
  4. 4Department of Paediatric Neurology, University of Moscow, Moscow, Russia
  1. Correspondence to:
 Dr Flavia di Michele, IRCCS Santa Lucia, via Ardeatina 306, 00179 Rome, Italy; 
 f.dimichele{at}hsantalucia.it

Abstract

Background: The neuroactive steroid 3α, 5α-tetrahydroprogesterone is the most potent endogenous positive modulator of γ-amino-butyric acid (GABA)A receptors. There is evidence for a relation between neuroactive steroids and seizure susceptibility.

Objective: To evaluate the putative role of counteregulator neuroactive steroids in the occurrence of seizures in patients with tuberous sclerosis.

Methods: Plasma concentrations of the enantiomers 3α, 5α- and 3α, 5β-tetrahydroprogesterone (3αs-THP), which are positive modulators of GABAA receptors, were measured in 18 patients, along with their endogenous functional antagonists 3β, 5α- and 3β, 5β-THP (3βs-THP), to assess their possible modification compared with control subjects. Neuroactive steroids were assayed using a highly sensitive and specific gas chromatographic/mass spectrometric method.

Results: In the tuberous sclerosis patients with poorly controlled seizures, there was a significantly lower 3αs/3βs-THP ratio than in seizure-free patients or control subjects.

Conclusions: The reduced 3αs/3βs-THP ratio may decrease GABAergic tone, contributing to the appearance of seizures in tuberous sclerosis patients with epilepsy.

  • tetrahydroprogesterone
  • epilepsy
  • neuroactive steroids
  • tuberous sclerosis
  • GABA
  • γ-amino-butyric acid
  • 3αs-THP, 3α, 5α- and 3α, 5β-tetrahydroprogesterone
  • 3βs-THP
  • 3β
  • 5α- and 3β
  • 5β-THP (functional antagonists of 3αs-THP

https://doi.org/10.1136/jnnp.74.5.667

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    Footnotes

    • Competing interests: none declared