Testosterone modulation of seizure susceptibility is mediated by neurosteroids 3α-androstanediol and 17β-estradiol

@article{Reddy2004TestosteroneMO,
  title={Testosterone modulation of seizure susceptibility is mediated by neurosteroids 3$\alpha$-androstanediol and 17$\beta$-estradiol},
  author={Doodipala Samba Reddy},
  journal={Neuroscience},
  year={2004},
  volume={129},
  pages={195-207}
}
  • D. Reddy
  • Published 31 December 2004
  • Biology, Medicine
  • Neuroscience
View on Elsevier
doi.org
125 Citations
Highly Influential Citations
5
Background Citations
50
Methods Citations
3
Results Citations
6

125 Citations

Citation Type

Citation Type

The Testosterone-Derived Neurosteroid Androstanediol Is a Positive Allosteric Modulator of GABAA Receptors
TLDR
Androstanediol could be a neurosteroid mediator of testosterone actions on neuronal excitability and seizure susceptibility via its activity as a GABAA receptor modulator and that androStanediol may play a key role in men with epilepsy, especially during the age-related decline in androgen levels.
Aromatase inhibition by letrozole attenuates kainic acid-induced seizures but not neurotoxicity in mice
The Effect of Androsterone as the Metabolite of Testosterone to Seizure Suppression
TLDR
The results suggest that androsterone exhibits anticonvulsant activity that occurs largely via nongenomic mechanisms and might be an endogenous protective neuroactive steroid in the brain.
Mass spectrometric assay and physiological–pharmacological activity of androgenic neurosteroids
  • D. Reddy
  • Biology, Medicine
    Neurochemistry International
  • 2008
Aromatase inhibitors as add–on treatment for men with epilepsy
TLDR
It was concluded that aromatase inhibitors may be a useful adjunct to the treatment of epilepsy, but habituation to thetreatment may be limiting, as many men with epilepsy have low testosterone, and aromat enzyme inhibition may be helpful in restoring levels to normal.
Role of Anticonvulsant and Antiepileptogenic Neurosteroids in the Pathophysiology and Treatment of Epilepsy
  • D. Reddy
  • Biology, Medicine
    Front. Endocrin.
  • 2011
TLDR
There is emerging evidence that endogenous neurosteroids may play a key role in the pathophysiology of catamenial epilepsy, stress–sensitive seizure conditions, temporal lobe epilepsy, and alcohol-withdrawal seizures.
Reduced estradiol synthesis by letrozole, an aromatase inhibitor, is protective against development of pentylenetetrazole-induced kindling in mice
Antiseizure effects of 3α-androstanediol and/or 17β-estradiol may involve actions at estrogen receptor β
Anti‐epileptic drug phenytoin enhances androgen metabolism and androgen receptor expression in murine hippocampus
TLDR
It is concluded that phenytoin affects testosterone metabolism via induction of CYP isoforms due to the increased metabolism of testosterone leading to augmented androgen metabolite formation most likely led to enhanced expression of CyP19 and AR in hippocampus.
Chronic levetiracetam decreases hippocampal and testicular aromatase expression in normal but not kainic acid-induced experimental model of acute seizures in rats
TLDR
The results suggest that levetiracetam decreases aromatase levels in the testis and increases the seizure threshold by a possible decrease in systemic estradiol levels.
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References

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Stress-Induced Deoxycorticosterone-Derived Neurosteroids Modulate GABAA Receptor Function and Seizure Susceptibility
TLDR
Evidence is provided that GABAA receptor-modulating neurosteroids derived from deoxycorticosterone play a role in stress-related changes in seizure control and that DOC is a mediator of the physiological effects of acute stress that could contribute to stress-inducedChanges in seizure susceptibility.
Anticonvulsant activity of the testosterone-derived neurosteroid 3&agr;-androstanediol
  • D. Reddy
  • Biology, Medicine
    Neuroreport
  • 2004
TLDR
The results suggest that testosterone-derived 3&agr;-androstanediol has powerful anticonvulsant activity that occurs largely through non-genomic mechanisms.
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In this model, withdrawal of progesterone leads to increased seizure susceptibility and insensitivity to benzodiazepine sedatives through an effect on gene transcription, which is due to reduced levels of 3α,5α-THP which enhance transcription of the α4 subunit of the GABAA receptor.
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  • Biology, Medicine
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TLDR
The enhanced anticonvulsant potency of ganaxolone after neurosteroid withdrawal supports the use of ganolone as a specific treatment for perimenstrual catamenial epilepsy.
ANDROGENIC NEUROSTEROIDS: ANTI-SEIZURE EFFECTS IN AN ANIMAL MODEL OF EPILEPSY
Testosterone and its metabolites affect afterdischarge thresholds and the development of amygdala kindled seizures
Anticonvulsant profile of the progesterone metabolite 5α-pregnan-3α-ol-20-one
Anticonvulsant activity of neurosteroids: correlation with gamma-aminobutyric acid-evoked chloride current potentiation.
TLDR
Although the anticonvulsant steroids had greater in vitro potencies than clonazepam, they were less potent in vivo, and they had lower protective indices.
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