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Modulation of androgen and estrogen receptor expression by antiepileptic drugs and steroids in hippocampus of patients with temporal lobe epilepsy
Epilepsia, 06/05/09

Killer N et al. – Results show that P450-inducing antiepileptic drugs (AEDs) influence AR expression and signaling in hippocampus, most likely via cytochrome (CYP) 3A4/11-induction. The HN25.1 cell line is promising for study of correlation between drug application and androgen receptor (AR) regulation and to specifically address issues relevant to human temporal lobe epilepsy (TLE) pts.

• Study of the expression of AR, estrogen receptor α (ERα), and CYP3A in the hippocampus of TLE patients and in murine hippocampal cell line HN25.1
• Treatment of pts and cell lines with P450-inducing or -noninducing AEDs or with prednisolone
• Application to prevent edema formation prior to neurosurgical resection of epileptic hippocampus
• Immunohistochemical analysis of human pt samples
• Quantitative RT-PCR, CAT reporter gene assay, and immunoblot of HN25.1 cell line

• In both humans and cell lines, expression of testosterone metabolizing CYP3A4 (human) or CYP3A11 (mouse) and AR was upregulated by application of P450-inducing AEDs and/or prednisolone
• AR-responsive CAT reporter gene assay showed increased AR-signaling after treatment of HN25.1 cells with the P450-inducers phenytoin and carbamazepine
• ERα expression increased only by P450-inducing AEDs, but not by prednisolone, indicating that pathways different from CYP3A4/11 led to ERα enhancement

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