Characterization of 17beta-hydroxysteroid dehydrogenase activity in brain tissue: testosterone formation in the human temporal lobe.
Sex steroids exert important effects on the central nervous system (CNS). Although the formation of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) metabolites in the CNS was discovered almost 30 years ago, conclusive studies concerning 17beta-HSD activity in the human brain are still lacking. Therefore, we investigated 17beta-HSD in vitro activity in human temporal lobe biopsies of 13 women and 13 men using radioactively labelled androstenedione, testosterone, oestrone and 17beta-oestradiol and compared it to that in human placenta, liver, testis and prostate. We could demonstrate androgenic and oestrogenic 17beta-HSD activities in all tissues under investigation. The reduction of androstenedione and oestrone in brain was NADPH dependent with a broad pH optimum between 6.5 and 9.0, whereas the oxidation of testosterone and 17beta-oestradiol was NAD dependent with a pH optimum of >/=9.0. Using optimum cofactors sex differences of brain 17beta-HSD activities were not observed. Conversion of androstenedione, testosterone, oestrone and 17beta-oestradiol was significantly higher in the subcortical white matter than in the cerebral cortex. We could demonstrate a significant formation of testosterone in the brain tissue of all patients under investigation. Substrate specificity and cofactor requirement patterns as well as pH optima and kinetic properties suggest the occurrence of 17beta-HSD type 3 and type 4 in the human temporal lobe.
Steckelbroeck
S
S
Department of Clinical Biochemistry, University of Bonn, Bonn, Germany. St_Steckelbroeck@hotmail.com
Stoffel-Wagner
B
B
Reichelt
R
R
Schramm
J
J
Bidlingmaier
F
F
Siekmann
L
L
Klingmüller
D
D
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000735:Androstenedione / Q000493:pharmacokinetics; D001711:Biotransformation; D001921:Brain / Q000201:enzymology*; D002540:Cerebral Cortex / Q000378:metabolism; D002855:Chromatography, Thin Layer; D004833:Epilepsy, Temporal Lobe / Q000201:enzymology; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D013379:Substrate Specificity; D013702:Temporal Lobe / Q000201:enzymology / Q000378:metabolism*; D013739:Testosterone / Q000096:biosynthesis*
D013739:Testosterone; D000735:Androstenedione; D015067:17-Hydroxysteroid Dehydrogenases