Expression of 5alpha-reductase and 3alpha-hydroxisteroid oxidoreductase in the hippocampus of patients with chronic temporal lobe epilepsy.
OBJECTIVE
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.
Stoffel-Wagner
B
B
Department of Clinical Biochemistry, University of Bonn, Germany.
Beyenburg
S
S
Watzka
M
M
Blümcke
I
I
Bauer
J
J
Schramm
J
J
Bidlingmaier
F
F
Elger
C E
CE
D015096:3-Hydroxysteroid Dehydrogenases / Q000032:analysis / Q000378:metabolism*; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000032:analysis / Q000378:metabolism*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000328:Adult; D000367:Age Factors; D002648:Child; D004833:Epilepsy, Temporal Lobe / Q000201:enzymology* / Q000378:metabolism / Q000601:surgery; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000201:enzymology* / Q000601:surgery; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D011374:Progesterone / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007527:Isoenzymes; D012333:RNA, Messenger; D011374:Progesterone; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase