Document Detail


Selective conversion by microglia of dehydroepiandrosterone to 5-androstenediol-A steroid with inherent estrogenic properties.
MedLine Citation:
PMID:  17681749     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The well-established neuroprotective effect of dehydroepiandrosterone (DHEA) has been attributed to its metabolism in the brain to provide estrogens known to be neuroprotective and to enhance memory and learning in humans and animals. However, our previous work showed that the conversion of DHEA to 4-androstenedione (AD), the precursor of estrone (E(1)) and estradiol (E(2)), is very low in several different types of neural cells, and that the main product is 7alpha-hydroxy-DHEA (7alpha-OH-DHEA). In this study, we found that microglia are an exception and produce mainly 5-androstene-3beta,17beta-diol (Delta(5)-Adiol), a C(19) steroid with estrogen-like activity from DHEA. Virtually, no other products, including testosterone (T) were detected by TLC or HPLC in incubations of (3)H-labeled DHEA with the BV2 microglial cell line. Microglia are important brain cells that are thought to play a house-keeping role during the steady state, and that are crucial to the brain's immune reaction to injury and the healing process. Our findings suggest that the microglia-produced Delta(5)-Adiol might have a role in modulating estrogen-sensitive neuroplastic events in the brain, in the absence of adequate local synthesis of estrone and estradiol.
Authors:
Peter H Jellinck; Martin Kaufmann; Andres Gottfried-Blackmore; Bruce S McEwen; Glenville Jones; Karen Bulloch
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-06-22
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  107     ISSN:  0960-0760     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:    2007 Nov-Dec
Date Detail:
Created Date:  2007-09-17     Completed Date:  2007-11-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  156-62     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada.
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MeSH Terms
Descriptor/Qualifier:
Androstenediol / metabolism*
Animals
Cell Line
Chromatography, High Pressure Liquid
Dehydroepiandrosterone / metabolism*
Estrogens / metabolism*
Mice
Microglia / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
5PSOAG16765//PHS HHS; NS07080/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Estrogens; 521-17-5/Androstenediol; 53-43-0/Dehydroepiandrosterone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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