Document Detail

11β-hydroxysteroid dehydrogenase type 2 in zebrafish brain: a functional role in HPI axis regulation.
MedLine Citation:
PMID:  23042946     Owner:  NLM     Status:  Publisher    
The type 2 11β-hydroxysteroid dehydrogenase (11βHSD2) converts active glucocorticoids to their inactive derivatives (ex. cortisol to cortisone). In most vertebrates, 11βHSD2 is essential for conferring aldosterone-specific actions in mineralocorticoid target tissues and for protecting glucocorticoid-sensitive tissues during stress. However, teleosts do not synthesize aldosterone, and the function of 11βHSD2 is poorly defined. The distribution of 11βHSD2 in non-mammalian brain is also largely unexplored. We tested the hypothesis that modulation of brain 11βHSD2 activity is involved in the stressor-mediated cortisol regulation in zebrafish (Danio rerio). In adult zebrafish, the stress effect on 11βHSD2 expression in the brain was tested using an acute air exposure followed by recovery over a 24 h period. 11βhsd2 transcripts were found in nearly all peripheral tissues examined, and a spatial map of its mRNA abundance in unstressed zebrafish brain revealed extensive distribution. Stressor exposure increased the conversion of 3H-cortisol to 3H-cortisone indicating enhanced 11βHSD2 activity in zebrafish brain. Promoter analysis of zebrafish 11βhsd2 gene revealed putative sites for cortisol-mediated transcriptional regulation of this gene. Furthermore, inhibition of 11βHSD2 activity by 18β-glycyrrhetinic acid resulted in elevated whole body cortisol levels and preoptic area mRNA abundance of corticotropin-releasing factor and mineralocorticoid receptor. Taken together, our results underscore an important role for brain 11βHSD2 involvement in the negative feedback regulation of cortisol post-stress in zebrafish.
Sarah L Alderman; Matt M Vijayan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-5
Journal Detail:
Title:  The Journal of endocrinology     Volume:  -     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
S Alderman, Biology, University of Waterloo, Waterloo, Canada.
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