GABA(A) receptor active steroids are altered in epilepsy patients with tuberous sclerosis.
BACKGROUND
The neuroactive steroid 3alpha, 5alpha-tetrahydroprogesterone is the most potent endogenous positive modulator of gamma-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 3alpha, 5alpha- and 3alpha, 5beta-tetrahydroprogesterone (3alpha(s)-THP), which are positive modulators of GABA(A) receptors, were measured in 18 patients, along with their endogenous functional antagonists 3beta, 5alpha- and 3beta, 5beta-THP (3beta(s)-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 3alpha(s)/3beta(s)-THP ratio than in seizure-free patients or control subjects.


CONCLUSIONS
The reduced 3alpha(s)/3beta(s)-THP ratio may decrease GABAergic tone, contributing to the appearance of seizures in tuberous sclerosis patients with epilepsy.
di Michele
F
F
Neuroendocrinology Laboratory, IRCCS Santa Lucia, Rome, Italy. f.dimichele@hsantalucia.it
Verdecchia
M
M
Dorofeeva
M
M
Costamagna
L
L
Bernardi
G
G
Curatolo
P
P
Romeo
E
E
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility / Q000097:blood / Q000503:physiopathology; D004827:Epilepsy / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D018756:GABA Antagonists / Q000097:blood; D018757:GABA Modulators / Q000097:blood; D006801:Humans; D007223:Infant; D007536:Isomerism; D008297:Male; D011280:Pregnanolone / Q000097:blood* / Q000502:physiology; D011963:Receptors, GABA-A / Q000097:blood* / Q000502:physiology; D014402:Tuberous Sclerosis / Q000097:blood* / Q000150:complications* / Q000503:physiopathology
D018756:GABA Antagonists; D018757:GABA Modulators; D011963:Receptors, GABA-A; D011280:Pregnanolone