help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Steckelbroeck, S.
Right arrow Articles by Klingmüller, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Steckelbroeck, S.
Right arrow Articles by Klingmüller, D.
The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 3 1324-1331
Copyright © 2001 by The Endocrine Society

Original Studies

Characterization of the 5{alpha}-Reductase-3{alpha}-Hydroxysteroid Dehydrogenase Complex in the Human Brain1

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

Departments of Clinical Biochemistry (S.S., M.W., R.R., B.S.-W., D.D.H., 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-53127 Bonn, Germany. E-mail: st_steckelbroeck{at}hotmail.com

Although androgen metabolism in the human brain was discovered almost 30 yr ago, conclusive studies on the enzymes involved are still lacking. We therefore investigated 5{alpha}-reductase and colocalized 3{alpha}-hydroxysteroid dehydrogenase (3{alpha}-HSD) activity in cerebral neocortex (CX) and subcortical white matter (SC) specimens neurosurgically removed from 44 patients suffering from epilepsy. We could demonstrate the presence of the 5{alpha}-reductase-3{alpha}-HSD complex in the biopsies of all patients under investigation. Inhibition experiments with specific inhibitors for 5{alpha}-reductase type 1 and type 2 revealed strong evidence for the exclusive activity of the type 1 isoform. We detected a significantly higher 5{alpha}-reductase activity in CX than in SC (P < 0.0001), but no sex-specific differences were observed. Furthermore, we found that, in contrast to liver, only 3{alpha}-HSD type 2 messenger RNA is expressed in the brain and that its expression is significantly higher in SC than in CX without sex-specific differences. The present study is the first to systematically characterize the 5{alpha}-reductase-3{alpha}-HSD complex in the human brain. The lack of sex-specific differences and also the colocalization of both enzymes at all life stages suggest a more general purpose of the complex, e.g. the synthesis of neuroactive steroids or the catabolism of neurotoxic steroids, rather than control of reproductive functions.




This article has been cited by other articles:


Home page
 Endocr. Rev.Home page
M. Schumacher, R. Guennoun, A. Ghoumari, C. Massaad, F. Robert, M. El-Etr, Y. Akwa, K. Rajkowski, and E.-E. Baulieu
Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System
Endocr. Rev., June 1, 2007; 28(4): 387 - 439.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
P. E. Alele and L. L. Devaud
Sex Differences in Steroid Modulation of Ethanol Withdrawal in Male and Female Rats
J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 427 - 436.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. C. Agis-Balboa, G. Pinna, A. Zhubi, E. Maloku, M. Veldic, E. Costa, and A. Guidotti
Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis
PNAS, September 26, 2006; 103(39): 14602 - 14607.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. A. Titus, C. W. Gregory, O. H. Ford III, M. J. Schell, S. J. Maygarden, and J. L. Mohler
Steroid 5{alpha}-Reductase Isozymes I and II in Recurrent Prostate Cancer
Clin. Cancer Res., June 15, 2005; 11(12): 4365 - 4371.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Steckelbroeck, Y. Jin, S. Gopishetty, B. Oyesanmi, and T. M. Penning
Human Cytosolic 3{alpha}-Hydroxysteroid Dehydrogenases of the Aldo-keto Reductase Superfamily Display Significant 3{beta}-Hydroxysteroid Dehydrogenase Activity: IMPLICATIONS FOR STEROID HORMONE METABOLISM AND ACTION
J. Biol. Chem., March 12, 2004; 279(11): 10784 - 10795.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. D. Wilson, R. J. Auchus, M. W. Leihy, O. L. Guryev, R. W. Estabrook, S. M. Osborn, G. Shaw, and M. B. Renfree
5{alpha}-Androstane-3{alpha},17{beta}-Diol Is Formed in Tammar Wallaby Pouch Young Testes by a Pathway Involving 5{alpha}-Pregnane-3{alpha},17{alpha}-Diol-20-One as a Key Intermediate
Endocrinology, February 1, 2003; 144(2): 575 - 580.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2001 by The Endocrine Society