Allopregnanolone serum levels and expression of 5α-reductase and 3α-hydroxysteroid dehydrogenase isoforms in hippocampal and temporal cortex of patients with epilepsy

In the human central nervous system, progesterone is rapidly metabolised to 5α-dihydroprogesterone which subsequently is further reduced to allopregnanolone (AP). These conversions are catalysed by 5α-reductase and 3α-hydroxysteroid dehydrogenase (3α-HSD). Although different isoforms of both enzymes have been identified in the brain, our knowledge of their expression in the human brain remains limited. The aim of the present study was to investigate the mRNA expression of 5α-reductase 1 as well as 3α-HSD 1, 2, 3 and 20α-HSD in brain tissue from patients with pharmacoresistant temporal lobe epilepsy (TLE). Specimens were derived from either the hippocampus or the temporal lobe cortex and from the tumor-free approach corridor tissue of patients with brain tumors. Quantification of different mRNAs was achieved by real time PCR. In addition, we provide data on simultaneous evaluation of serum AP concentrations. We could demonstrate that 3α-HSD 1 was not expressed in the hippocampus and temporal lobe of patients with TLE. In the hippocampus and temporal lobe, the expression levels of 3α-HSD 2 were about 20% of that in liver tissue, those of 3α-HSD 3 about 7% and those of 20α-HSD about 2%, respectively. In patients with TLE, expression of 3α-HSD 2 was significantly higher in the hippocampus than in temporal lobe cortex tissue (P<0.006). AP concentrations did not correlate significantly with the mRNA expression levels of 5α-reductase 1, 3α-HSD 2 and 3 and 20α-HSD in any of the patient groups under investigation. In conclusion, the present study demonstrates mRNA expression of 5α-reductase 1 and 3α-HSD 2 and 3 and 20α-HSD in the hippocampus and temporal lobe of epileptic patients. These findings provide further molecular biological evidence for the formation and metabolism of neuroactive steroids in the human brain.