Expression of 5α‐Reductase and 3α‐Hydroxisteroid Oxidoreductase in the Hippocampus of Patients with Chronic Temporal Lobe Epilepsy

Abstract

PURPOSE: The hippocampus is one of the principal target areas for neurosteroidal action, and the major neuroendocrine conversion of progesterone appears to be 5alpha-reduction and 3alpha-hydroxysteroid oxidoreduction, leading to the potent neurosteroid 3alpha,5alpha-tetrahydroxyprogesterone. To investigate whether the human hippocampus is equipped with the enzymes 5alpha-reductase and 3alpha-hydroxysteroid oxidoreductase (3alpha-HSOR), we studied the expression of 5alpha-reductase types 1 and 2 and 3alpha-HSOR types 1 and 2 in the resected hippocampi of patients with medically intractable chronic temporal lobe epilepsy. METHODS: We studied tissue specimens from the hippocampi of 13 women, 25 men, and four children. Quantification of different mRNAs was achieved by competitive reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: 5Alpha-reductase 1 mRNA and 3alpha-HSOR 2 mRNA were expressed in hippocampi of children and adults, whereas 5alpha-reductase 2 mRNA and 3alpha-HSOR 1 mRNA were not expressed. Neither 5alpha-reductase 1 mRNA nor 3alpha-HSOR 2 mRNA concentrations in hippocampal tissue showed any statistically significant differences between women and men or between children and adults. CONCLUSIONS: This study demonstrates for the first time mRNA expression of the type 1 isozyme of 5alpha-reductase and the type 2 isozyme of 3alpha-HSOR in the human hippocampus. The finding that both 5alpha-reductase and 3alpha-HSOR are present in the hippocampus leads us to assume the synthesis of neuroactive steroids in this human brain area.