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The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 8 2795-2801
Copyright © 1999 by The Endocrine Society

Original Studies

Characterization of Aromatase Cytochrome P450 Activity in the Human Temporal Lobe1

Stephan Steckelbroeck, Dagmar D. Heidrich, Birgit Stoffel-Wagner, Volkmar H. J. Hans, Johannes Schramm, Frank Bidlingmaier and Dietrich Klingmüller

Departments of Clinical Biochemistry (S.S., D.D.H., B.S.-W., F.B., D.K.), Neuropathology (V.H.J.H.), and Neurosurgery (J.S.), University of Bonn, 53105 Bonn, Germany

Address all correspondence and requests for reprints to: Dr. Stephan Steckelbroeck, Institut für Klinische Biochemie, Universität Bonn, Sigmund Freud Strasse 25, D-53105 Bonn, Germany. E-mail: st_steckelbroeck{at}hotmail.com

Local aromatase-mediated conversion of androgens plays an important role in androgen action on the brain. To characterize estrogen formation in the human brain, we measured the microsomal aromatase activity of temporal lobe biopsies and compared it to that of human placenta using a highly sensitive 3H2O assay with [1ß-3H]androstenedione as substrate. Brain tissue was removed neurosurgically from 23 patients with epilepsy. Data of kinetic 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 had to be corrected for nonspecific tritium release. The mean Km values were 22.2 nmol/L in brain and 49.6 nmol/L in placenta. Inhibition experiments with atamestane, an inhibitor of aromatase cytochrome P450, revealed specific, dose-responsive, and competitive inhibition of both brain and placental aromatase activities. Placental aromatase activity was completely suppressible by atamestane, whereas in brain tissue there remained a residue of nonspecific tritium release. Subsequent experiments with cerebral cortex and subcortical white matter specimens of children and adults revealed a significantly higher aromatase activity in cerebral cortex than in subcortical white matter, but no sex or age differences were found.




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