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Characterization of the dehydroepiandrosterone (DHEA) metabolism via oxysterol 7α‐hydroxylase and 17‐ketosteroid reductase activity in the human brain by Stephan Steckelbroeck; Matthias Watzka; Dieter Lütjohann; Paul Makiola; Alexander Nassen; Volkmar H. J. Hans; Hans Clusmann; Annette Reissinger; Michael Ludwig; Lothar Siekmann; Dietrich Klingmüller is a Neuroscience article available to read on EtoBox.
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## Abstract Dehydroepiandrosterone and its sulphate are important factors for vitality, development and functions of the CNS. They were found to be subjects to a series of enzyme‐mediated conversions within the rodent CNS. In the present study, we were able to demonstrate for the first time that membrane‐associated dehydroepiandrosterone 7α‐hydroxylase activity occurs within the human brain. The cytochrome P450 enzyme demonstrated a sharp pH optimum between 7.5 and 8.0 and a mean __K__~M~ value of 5.4 μm, corresponding with the presence of the oxysterol 7α‐hydroxylase CYP7B1. Real‐time RT–PCR analysis verified high levels of CYP7B1 mRNA expression in the human CNS. The additionally observed conversion of dehydroepiandrosterone via cytosolic 17β‐hydroxysteroid dehydrogenase activity could be ascribed to the activity of an enzyme with a broad pH optimum and an undetectably high __K__~M~ value. Subsequent experiments with cerebral neocortex and subcortical white matter specimens revealed that 7α‐hydroxylase activity is significantly higher in the cerebral neocortex than in the subcortical white matter (__p__ < 0.0005), whereas in the subcortical white matter, 17β‐hydroxysteroid dehydr
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- Author
- Stephan Steckelbroeck; Matthias Watzka; Dieter Lütjohann; Paul Makiola; Alexander Nassen; Volkmar H. J. Hans; Hans Clusmann; Annette Reissinger; Michael Ludwig; Lothar Siekmann; Dietrich Klingmüller
- Publisher
- John Wiley and Sons; Wiley (Blackwell Publishing); Blackwell Publishing Inc.; Wiley (ISSN 0022-3042)
- Published
- 2002
- Language
- EN
- Field
- Neuroscience (Life Sciences)