Characterization of 17β-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 17β-hydroxysteroid dehydrogenase (17β-HSD) metabolites in the CNS was discovered almost 30 years ago, conclusive studies concerning 17β-HSD activity in the human brain are still lacking. Therefore, we investigated 17β-HSD in vitro activity in human temporal lobe biopsies of 13 women and 13 men using radioactively labelled androstenedione, testosterone, oestrone and 17β-oestradiol and compared it to that in human placenta, liver, testis and prostate. We could demonstrate androgenic and oestrogenic 17β-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 17β-oestradiol was NAD dependent with a pH optimum of ≥9.0. Using optimum cofactors sex differences of brain 17β-HSD activities were not observed. Conversion of androstenedione, testosterone, oestrone and 17β-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 17β-HSD type 3 and type 4 in the human temporal lobe.