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 5α-reduction and 3α-hydroxysteroid oxidoreduction, leading to the potent neurosteroid 3α,5α- tetrahydroxyprogesterone. To investigate whether the human hippocampus is equipped with the enzymes 5α-reductase and 3α-hydroxysteroid oxidoreductase (3α-HSOR), we studied the expression of 5α-reductase types 1 and 2 and 3α- 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: 5α-Reductase 1 mRNA and 3α-HSOR 2 mRNA were expressed in hippocampi of children and adults, whereas 5α-reductase 2 mRNA and 3α-HSOR 1 mRNA were not expressed. Neither 5α-reductase 1 mRNA nor 3α-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 5α-reductase and the type 2 isozyme of 3α-HSOR in the human hippocampus. The finding that both 5α-reductase and 3α-HSOR are present in the hippocampus leads us to assume the synthesis of neuro-active steroids in this human brain area.