Characterization of aromatase cytochrome P450 activity in the human temporal lobe

Local aromatase-mediated conversion of androgens plays an important role in androgen action on the brain. To characterize estrogen formation in the hu man brain, we measured the microsomal aromatase activity of temporal lobe b iopsies and compared it to that of human placenta using a highly sensitive (H2O)-H-3 assay with [1 beta-H-3] androstenedione as substrate. Brain tissu e was removed neurosurgically from 23 patients with epilepsy. Data of kinet ic studies were analyzed with a computer-assisted, nonlinear, curve-fitting method using the Michaelis-Menten plus a nonspecific metabolism model. In contrast to data for placental aromatase activity, that for brain always ha d to be corrected for nonspecific tritium release. The mean K-m values were 22.2 nmol/L in brain and 49.6 nmol/L in placenta. Inhibition experiments w ith atamestane, an inhibitor of aromatase cytochrome P450, revealed specifi c, dose-responsive, and competitive inhibition of both brain and placental aromatase activities. Placental aromatase activity was completely suppressi ble by atamestane, whereas in brain tissue there remained a residue of nons pecific tritium release. Subsequent experiments with cerebral cortex and su bcortical white matter specimens of children and adults revealed a signific antly higher aromatase activity in cerebral cortex than in subcortical whit e matter, but no sex or age differences were found.