Expression of 5 alpha-reductase and 3 alpha-hydroxisteroid oxidoreductase in the hippocampus of patients with chronic temporal lobe epilepsy

Purpose: The hippocampus is one of the principal target areas for neuroster oidal action, and the major neuroendocrine conversion of progesterone appea rs to be 5 alpha-reduction and 3 alpha-hydroxysteroid oxidoreduction, leadi ng to the potent neurosteroid 3 alpha,5 alpha-tetrahydroxyprogesterone. To investigate whether the human hippocampus is equipped with the enzymes 5 al pha-reductase and 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR), we studied the expression of 5 alpha-reductase types 1 and 2 and 3 alpha-HSOR types 1 and 2 in the resected hippocampi of patients with medically intract able chronic temporal lobe epilepsy. Methods: We studied tissue specimens from the hippocampi of 13 women, 25 me n, and four children. Quantification of different mRNAs was achieved by com petitive reverse transcription-polymerase chain reaction (RT-PCR). Results: 5 alpha-Reductase 1 mRNA and 3 alpha-HSOR 2 mRNA were expressed in hippocampi of children and adults, whereas 5 alpha-reductase 2 mRNA and 3 alpha-HSOR 1 mRNA were not expressed. Neither 5 alpha-reductase 1 mRNA nor 3 alpha-HSOR 2 mRNA concentrations in hippocampal tissue showed any statist ically significant differences between women and men or between children an d adults. Conclusions: This study demonstrates for the first time mRNA expression of the type 1 isozyme of 5 alpha-reductase and the type 2 isozyme of 3 alpha-H SOR in the human hippocampus. The finding that both 5 alpha-reductase and 3 alpha-HSOR are present in the hippocampus leads us to assume the synthesis of neuroactive steroids in this human brain area.