Document Detail


Hippocampal 11beta-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid expression has a diurnal variability that is lost in the obese Zucker rat.
MedLine Citation:
PMID:  17332068     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Circulating levels of glucocorticoids show a circadian rhythm. Obesity is associated with a flattening of the diurnal rhythm; plasma cortisol levels are slightly increased during the trough, although they are normal or low in the morning. Studies in humans and in leptin-resistant Zucker rats suggest that tissue-specific alterations in glucocorticoid exposure might play a key role for development of obesity and obesity-associated dysregulation of the hypothalamic-pituitary-adrenal axis. We hypothesized that there is a circadian rhythm in prereceptor metabolism of glucocorticoids exerted by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in brain and/or peripheral tissues (liver, fat, and muscle) that might be abrogated in obesity. The present study demonstrates a circadian rhythm in 11beta-HSD1 mRNA expression (35-45% increase at morning vs. evening, P < 0.05) in dentate gyrus granular layer and CA1 subregions of the hippocampus in lean Zucker rats that was lost in the obese rats. Sprague Dawley rats also revealed a diurnal rhythm in hippocampal 11beta-HSD1 mRNA expression. There was no circadian variation in 11beta-HSD enzyme activity in peripheral tissues, although obese Zucker rats had a decreased enzyme activity in liver and epididymal fat (by approximately 40%, P < 0.05) compared with lean rats. In Sprague Dawley rats, 11beta-HSD activity in adipose tissue was higher in retroperitoneal and epididymal vs. sc fat (P < 0.001). In summary, obese Zucker rats lack a circadian rhythm of 11beta-HSD1 gene expression in the hippocampus, which may contribute to increased activity of the hypothalamic-pituitary-adrenal axis and altered diurnal variation of circulating corticosterone levels.
Authors:
Jonas Burén; Sven-Anders Bergström; Edmund Loh; Ingegerd Söderström; Tommy Olsson; Cecilia Mattsson
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-03-01
Journal Detail:
Title:  Endocrinology     Volume:  148     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-17     Completed Date:  2007-07-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2716-22     Citation Subset:  AIM; IM    
Affiliation:
Department of Public Health and Clinical Medicine, Umeå University Hospital, SE-901 85 Umeå, Sweden. jonas.buren@medicin.umu.se
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MeSH Terms
Descriptor/Qualifier:
11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics*,  metabolism
Animals
Cerebral Cortex / enzymology,  metabolism
Circadian Rhythm*
Corticosterone / blood
Gene Expression Regulation, Enzymologic
Hippocampus / enzymology,  metabolism*
Male
Obesity / blood,  enzymology,  genetics*
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Rats, Zucker
Chemical
Reg. No./Substance:
0/RNA, Messenger; 50-22-6/Corticosterone; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 1

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


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