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

In the human central nervous system, progesterone is rapidly metabolised to 5alpha-dihydroprogesterone which subsequently is further reduced to allopregnanolone (AP). These conversions are catalysed by 5alpha-reductase and 3alpha-hydroxysteroid dehydrogenase (3alpha-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 5alpha-reductase 1 as well as 3alpha-HSD 1, 2, 3 and 20alpha-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 3alpha-HSD I was not expressed in the hippocampus and temporal lobe of patients with TLE. In the hippocampus and temporal lobe, the expression levels of 3alpha-HSD 2 were about 20% of that in liver tissue, those of 3alpha-HSD 3 about 7% and those of 20alpha-HSD about 2%, respectively. In patients with TLE. expression of 3alpha-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 5alpha-reductase 1, 3alpha-HSD 2 and 3 and 20a-HSD in any of the patient groups under investigation. In conclusion, the present study demonstrates mRNA expression of 5alpha-reductase 1 and 3alpha-HSD 2 and 3 and 20alpha-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. (C) 2003 Elsevier Science B.V. All rights reserved.